Topic Subtopic Note
AIDS CNS- d/t HIV, Opportunistic infections, Neoplasm
In HIV pt the most common brain lesions- toxo, B cell NHL, pyogenic abcess, syphylis, PML, mets
Tx of toxo- pyrimethamine and sulfadiazine are of initial benefit in up to 90% of patients. most adult in US have ab indicative of prior exposure. Cerebral involvement is thought to represent reactivation of a late primary infection.
AIDS dementia- subcortical, PM slow, impaired concentration, reading and forgetfulness
Chronic alcoholic hallucinosis is characterized by auditory hallucinations with a clear sensorium.
DT 3-21 days
DT 3 days-3 weeks
some believe if happen after 5 days it is not DT according to Dr. Ross
DT is dx of exclusion why pt stopped drinking if no money they also may have SDH, MI, meningitis, pancreatitis, bowel obstruction, ....
mortality 20-30% s tx
DT can go on for 1-2 days
string sign pt can not identify color of string also happens in other delirious states
In Wernicke-Korsakoff syndrome, lesions are located in the periventricular gray matter, periaqueductal gray matter, mamillary bodies, and floor of the fourth ventricle.
cerebellum purkinjee cells, mamillary body, dorsomedial thalamus, dorsolat prefrontal, periaquductal gray matter
Wernicke- ataxia, nystagmus, ophthalmoplegia or ocular dyskinesia, lethargy inattentiveness
Korsakoff- antegrade amnesia and patchy longterm memory, confabulation, opposite TGA not stressed about their amnesia
Korsakoff amnestic synd:
-impairment in verbal learning antgrade amnesia
- forgetting recent events retrograde amnesia
- motor and semantic memory(word meaning) as well as digit span are normal.
Antegrade/recent memory impaired immediate/remote memory intact
remote recent immediate antegrade memory

Methanol intoxication results in severe metabolic acidosis due to oxidation of methanol to formic acid. Dilated, unreactive pupils and reduced vision are typical, due to destruction of retinal ganglion cells. Bicarbonate is the keystone of treatment of methanol poisoning. Concomitant administration of ethanol, a competitive substrate of alcohol dehydrogenase, may have some benefit. A loading dose (0.6 g/kg) should be administered as soon as the diagnosis of methanol poisoning is made.
Fetal alcohol synd. ASD, Microcephaly, growth retardation
Behavioral neurology
Alien Hand Syndrome:
2 form
Dysparetic: intramanual conflict, mirror movement, interference etc in Corticobasal ganglionic degeneration associated with parietal/frontal lobe degeneration and has cortical sensory loss, regidity/myoclonus and alien hand synd. and speech gait apraxia
Frontal lobe reflexes: groping, grasping with inability to release, misutilization etc associated with ACA stroke A comm anurysm corpus callusom lesion tumor Marchiafava Bignami
Behavioral neurology
Antipsychotic tx
for tx effectiveness 65% D2 blockade
Prolactin elevation 75%
EPS to occure >80% D2 blockage needed.
3D of psychosis
Dementia, Delirium, Depression
tx of agitation in pt c dementia
- trazodone 50-250 mg/d
-haloperidole 1-5 mg/d esp for aggression not agitation
- behavior manageement techniques
- atypical antipsychotics
risperidone low DM revelation, inc stroke risk 3 times
olanzapine Zyprexa inc mortality inc DM
quitipone low DM, low EPS
aripiprazole 10 mg/day
they have
- no or low EPS, TD
- no sustained inc in prolactin
- reduce neg symptoms (typical reduce positive symptoms)
Behavioral neurology
Callosal apraxia results from a lesion in the genu of the corpus callosum. This results in a left limb kinetic apraxia. Tactile and auditory input cross the corpus callosum posteriorly and are therefore unaffected by a genu lesion. Alexia without agraphia results from a left occipital splenium of the corpus callosum lesion.
Witzelsucht (inappropriate jocularity) is seen in patients with orbitofrontal cortex lesions. Lesions in the orbitofrontal cortex also include disinhibited and antisocial behavior.

Behavioral neurology
statue synd
- immobility/waxy flexibility/posture
- mutism/analgesia
- mannerism/rituals
- grimacing/shoulder shrug
- psychosocial withdrawal/stupor

Catatonia is a syndrome manifested by a number of motor and neuro behavioral features. It may have a "retarded-stuporous" form or an "excited-delirious" form. It may be seen in over 10% of inpatient psychiatric patients. Catatonia is more prevalent in mood disorders than in schizophrenia. The most common mood disorder in which it is seen is bipolar. Catalepsy, waxy flexibility, echophenomena, and negativism including mutism are common. Many neurological and systemic illnesses may also present as catatonia. Treatments include benzodiazepines, barbiturates, and ECT. Dopamine antagonists (neuroleptics) as well as baclofen may worsen the condition.
Taylor MA, Fink M. Catatonia in psychiatric classification: a home of its own. Am J Psychiatry 2003;160:1233-1241.
Behavioral neurology
Frontal lobe syndromes
- medial: akinetic mutism, UI, bil leg weakness
- orbitofrontal: disinhibition, Witzelsucht (compulsion to say jokes funny only for the pt)or Witzelsucht (inappropriate jocularity)
- convexity: apathy, perseveration, poor sequencing
Reduplicative paramnesia- person believes is in two place at once, in bilat frontal and R parietal lobe lesion
Behavioral neurology
Ganser syndrome
is sometimes known as the "syndrome of approximate answers," or "pseudostupidity." Most often seen in psychiatic disorders, it has also been reported following neurologic conditions such as head trauma and neurosyphilis.
The presentation of disinhibited, poorly monitored verbal output that is socially unacceptable has been termed verbal dysdecorum and is seen most frequently following damage to the right frontal convexity.
frontal lobe syndromes
- medial: apathy, akinetic mutism, UI, bil leg weakness
- orbitofrontal: disinhibition
- convexity: apathy
Behavioral neurology
Geriatric neurology
special neurology issues in the elderly, common aging changes and impact on fx
GerNeur is pt disability based. fx and psychosocial issues.
Elderly- context/task specific, chronological, physical/functional, historical/societal (65yo),political
Geriatric synd c neurologic presentation:
- Altered MS, Delirium
- UI
- Gait instability/falls
Geriatric assessment:
H & P- MS, hearing,vision
Detailed med including OTC
Mood assessment
Nutrition/Skin status
Fx status continence,gait,finance
Socioeconomic status
Advance directive/discharge plan
driving and elderly-
if you concern can send a report to dept of public safety. It is not mandatory in OK. mandatory in CA, PA.
Behavioral neurology
Lewy body dementia
dementia, parkinsonism, visual hallucinations, sensitivity to neuroleptics
tx- Exelon is drug of choice, can use Serequel up to 100 mg qhs
Behavioral neurology
Neurodegeneeative disorders
cortex dementia
BG movement disorder
cerebellum ataxia
motor neuron weakness
Prion, toxin MPTP, Triplet repeat, oxidation
Cytoplasmic inclusions
structural pr stress pr
neurofilament Ubiquitin
Tau Crystalline
Synuclein Heat Shock pr
Neurodegenerative c dementia
1- Alz neurofilament tangles
2- Taupathies FTD, Pick, CBG, PSP
3- Synucleinopathies LBD, PD, MSA(OPCD, SND, SDrager,Parkinsonism-Amyotrophy)
Behavioral neurology
Occipital lobe syndromes
*Anton synd- cortical blindness. pt deny blindness bil O lesion calcarine
* Bonnet synd-formed stereotyped visual hallucinations
* (Disorder of visuospatial processing) Balint- impair visual scanning, inability to visually guide limb movement, in bilat OP junction lesions. components:
1- Simultan agnosia-visual disorientation
2- Optic ataxia-deficit of visual reaching (inability to visually guide limb movement)
3- Ocular apraxia- deficit of visual scanning
(Disorder of object recognition)
* Achromatopsia- loss of color vision in OT junction lesion (lingula-fusiform gyrus,nondominant)
* Color anomia- recognize the color can not name it
* Prosop agnosia- unable to recognize faces, bil inf visual association cortex(bil OT junction)
* Word blindness- Alexia s agraphia, L occiptal lesion near splenium of CC, associated c achromatopsia/color anomia and R hhemianopsia in L PCA stroke (emboli)
alexia c agraphia in angular gyrus of parietal lobe
Balint can be seen in Alz.
Prosopagnosia (inability to identify faces visually) is most often seen after bilateral inferior occipito-temporal lesions affecting both fusiform gyri. Similar bilateral lesions (or a nondominant lesion) of the fusiform and lingual gyri account for cerebral achromatopsia. Palinopsia (recurrence of a visual image after diverting gaze or when the stimulus object is withdrawn) occurs with occipito-temporal disease, often epileptogenic.
Behavioral neurology
Parietal lobe syndromes
- dominant: Gerstmann(finger agnosia, LR Confusion, acalculia, agraphia, +- alexia, more in inf parietal lesions)
- non dominant: neglect(autotopagnosia, apractagnosia), dressing apraxia, anosognosia, tactile allesthesia, receptive aprosodia
Behavioral neurology
Prosopagnosia (inability to identify faces visually) is most often seen after bilateral inferior occipito-temporal lesions affecting both fusiform gyri. Similar bilateral lesions (or a nondominant lesion) of the fusiform and lingual gyri account for cerebral achromatopsia. Palinopsia (recurrence of a visual image after diverting gaze or when the stimulus object is withdrawn) occurs with occipito-temporal disease, often epileptogenic. Alexia without agraphia (inability to read but with preserved writing ability) occurs with combined lesions of the dominant occipital lobe and the inferior splenium of the corpus callosum or with a single lesion of the dominant occipito-temporal paraventricular white matter behind, beneath, and beside the occipital horn of the lateral ventricle. Alexia with agraphia (central alexia) is usually due to an angular gyrus (parietal lobe) lesion.
Bilateral lesions of the amygdala result in the Kluver-Bucy syndrome. This syndrome is seen in herpes simplex encephalitis, Pick's disease, anoxic-ischemic lesions in the anterior medial temporal lobes, and after bilateral temporal lobectomy. It is rarely, if ever, seen as a manifestation of Creutzfeldt-Jakob, Alzheimer's or Huntington's disease. clinical features include- hyperorality, hypersexuality, blunt affect, hypermetamorphosis, visual agnosia
Contusion of the orbitofrontal cortex is associated with social disinhibition. Apathy, depression and loss of task set is more commonly seen in dorsolateral prefrontal lesions. Akinetic mutism is more commonly associated with medial frontal lesions.
Anosognosia (unawareness of deficit or illness) is usually seen associated with non-dominant parietal lobe lesions. Achromatopsia is found after lesions of the inferior lip of the occipital lobe. Limb kinetic apraxia is seen after lesions of the anterior corpus callosum. Expressive aprosodia is seen after right frontal lesions. Semantic aphasia is seen after dominant hemisphere lesions.
Behavioral neurology
Psychogenic amnesia
loss of remote memory (autobiography loss) plus no problem c new learning
d/t tia, sz, migraine, trauma
ddx wernicke, intoxication, dissociative states
repeat same question, stressed about situation opposite to Korsakof
intact cognition, language
profound antegrade amnesia and retrograde amnesia for preceding several hours or days
chance of recurrence eg 25% of pt
MRI c Sz protocol or stroke w/u
Behavioral neurology
Rapidly progressive dementia
-EEG for PLED EKG changes
- Cerebral angio
- Viral studies
IgG IgM for HSV, CMV, EBV , Rubella, Rubeola, HHV, HIV,
- ANCA, APL, Whipple
- SPEP, IFE, Amyloidosis
- Hepatitis profile, cryglobulin
- CSF cytology for malignancy
- Tick panel
- B12, FA, TSH, FT4
- Homocysteine
above causes
- Hashimoto encephalitis, check antithyroglobulins and anti thyroperoxidase
- Lewy BD
- Postviral encephalitis
- Paraneoplastic
- Anoxic brain injury
- CJD sporadic vs varient, associated with myoclonus, cerebellar ataxia, psychiatric symptoms, cortical blindness, akinetic mutism etc, MRI may show ribbon like high signal in cerebral cortex (or high signal in striatum) in DWI or high T2 signals in post thalamus pulvinar, inc pr 14-3-3, PLEDs on EEG, travel to UK
Sylvia Frazier E002184265
Behavioral neurology Language Aphasia is a disorder of language, to be distinguished from disorders of speech (dysarthria, dysphonia) and disorders of thought (e.g., dementia, confabulation, perseveration, agnosia). Aphasic utterances can involve nonexistent word forms called neologisms.
The characteristic feature of conduction aphasia is a striking deficit of repetition, with relative sparing of speech comprehension and output, though literal paraphasic errors may be present.
Decreased repetition is noted in all the presylvian aphasias, including Broca's, Wernicke's, conduction, and global aphasia. Repetition is generally spared in the transcortical aphasias.
Alexia without agraphia is often seen with lesions of the left occipital cortex that frequently are seen to extend into the splenium of the ipsilateral corpus callosum. Because of the occipital cortical involvement and splenial involvement, there may be associated color anomia and right homonomous hemianopia.
Aphemia writing is preserved, in Broca, TCMotorAphasia and MixedTCAphasia writing is impaired.

Borderzone stroke cause transcortical expressive and receptive aphasia. repetition is intact d/t sparing of perisylvian area.
SMA is pacemaker for verbal output.
Behavioral neurology Memory Alz gene
early onset AD
- APP gene on ch 21
- presenilin 1 on ch 14
- presenilin 2 on ch 1
late onset AD
- APOE4 on ch 19
- a2M gene on ch 12
anxiety, depression, Capgras synd common in Alz. depression also common in PD,Wilson,Huntington,MS
Intellectual fx- language, memory, visualspatial skills, emotion or personality, and cognition (abstraction, calculation, judgment, etc)
Dementia- acquired persistant impairment of at least 2 or 3 of the above spheres of mental activity.
Behavioral neurology Memory Digit span, which involves attentional processes, immediate recall and ability to sequence bits of information, may be reduced following lesions of dorsolateral frontal cortex. Lesions of the fornix, mammillary bodies and medial dorsal nucleus of the thalamus, on the other hand, cause amnesia (impaired secondary memory) without a reduction of digit span.
Galantamine is a therapeutic agent for Alzheimer's disease that acts by both inhibiting AChE and allosterically modulating nicotinic ACh receptors. Rivastigmine acts by inhibiting AChE and butyrylcholinesterase. Choline acetyltransferase is decreased in AD. Chromosomes 1, 14, 19, 21 and possibly 12 have been associated with the genetics of AD but not 3. Alpha secretase cleaves APP normally. Beta and gamma secretase have been implicated in the production of toxic beta amyloid.
Human prion diseases include kuru, sporadic Creutzfeldt-Jakob disease, iatrogenic Creutzfeldt-Jakob disease, new variant Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, and fatal familial insomnia.
The loss of remote memory including autobiographical memory in the face of intact new learning ability is consistent with psychogenic amnesia. I
One of the most striking characteristics of a patient with Pick's disease is a tendency to make the same statements repetitively (gramophone syndrome).
Although memory impairment has been attributed to frontal lobe dysfunction, true amnesia is uncommon with frontal lobe lesions. Inattention, distractibility, poor motivation, and impaired strategy formation lead to the forgetfulness associated with frontal lobe lesions. Lesions of the temporal lobe have been associated with pure amnesia and lesions of the occipital and parietal lobes or cerebellum do not produce forgetfulness.
The combination of early visual hallucinations, markedly fluctuating mental status, sensitivity to neuroleptics and lack of response to levodopa are characteristic of dementia with Lewy bodies.
Behavioral neurology Memory FTD
Pick can be associated c Kluver-Bucy synd (hyperorality, hypersexuality, plasticity) in addition to personality changes and dec impulse control. placidity lack of normal aggresiveness. FTD linked to ch. 17
thumb sign sup temp gyrus usually very thick b/o auditory reciever, but in FTD or Alz they become prominent in MRI.
- picks
- primary progressive aphasia/aprsodia
- Corticobasal ganglion degeneration
- post cortical atrophy (in parietal lobe)

dementia progressive decline in intellectual function that include not only memory but also language, agnosia, executive functions, ...
AntiCholinergics good for Lewy body dementia (visual allocination, delusions)opposite to other dementias.
Neuroleptics in dementia
haldol 0.5-2 mg/d
zyprexa 2.5-7.5 /d enhance cholinergic transmission
seroquel low EPs effects
vit e
Memantin NMDA antagonist
Behavioral neurology Treatment donpezil can be used in AD, Vascular dementia and mixed, MS, PD, ADHD, Closed head injury
Brain death
Vegetative state
- present sleep awake cycle
- present cn reflexes
- present autonomic hypothalamiçfunction
- unaware of self and environ
- no language understanding
- no purposeful voluntry movement

etio: diffuse axonal injury or post hypoxic ischemic encepaholopathy with laminar necrosis
thalamus or thalamo cortical fibers severely involved
nontraumatic very poor more than 3 m
traumatic very poor more than 12 month
ethic committee to decide
- some definite behavioral evidence of self or environmental awareness
can do simple commands, smile or cry, some verbalization
tx: neurorehabm, levodopa, dopamine agonists, SSRI, stimulant, Ambien
experiment: DBS in intralaminar nuclei

Brain death Brain death AAN
cessation ofall brain fx
proximate cause is known (no hypothermia or drug overdosage)
condition irreversible
- coma
- absent brain stem reflex
pupill light, corneal, nasal, OCephalic, OVestibular, gag
- Apnea test (no spontaneous respiration after 10 min or with PCO2 >60 -caution in using PCO2 for COPD pt) pt are ventilated for 10-30 min c 100% O2 (maintain baseline PCO2) and then disconnected from the ventilator while 100% O2 is given at >= 6 Lit/min. ABG is measured before the ventilator disconnected and 5-10 min after disconnecting the ventilator.
- eeg (some activity may persist in first 24 h after cessation of CBF)
- PET SPECT for CBFlow or Angio (earliest and most definitive proof of brain death)
- TCDoppler study
persistant vegetative state
wakefulness s cognition after recovery from coma
keep sleep-awake cycle and veggie fx
etio- HIE, Metabolic, Encephalitis, head trauma
AAN - All medical tx including nutrition, hydration MAY be ethically discontinued if it is clear the pt didn't want to be maintained on this AND family agree.
Children who remain in PVS for 3 months do not regain FUNCTIONAL skill.

order EEG at least 6 h after CP arrest as there may be a transient suppression following anoxic insult. A repeat EEG after 24 h may be helpful but flat EEG is not necessary for dx of brain death.
Prognostication is best evaluated 3-7 days after brain injury.
Clinical trials
inpt stroke care
screening for future fall risk
advance care plan
medication reconcilation
if 3 or more measure reported 80 percent of time eligible 1.5 percent bonus payment.
Clinical trials No Value Clinical trials in neurology
1- surgery for carotid disease
2- Aspirin dose for stroke prevention 81-325
3- WARRS trial- warfatin in non cardiogenic noncarotodogenic stroke has no advantage over ASA even in subgroup of pt with pfo, apl
ab synd. or large/small stroke
4- HOPE PROGRESS trial- ace i is good for stroke even in normotensives
5- STATIN AS CARE LIPID trial- statins are good for stroke
6- MATCH CURE trial plavix has added benefit with ASA
7- EVIDENCE study
Rebif 44 mcg Sc tiw c/t 30mcg Avonex im qweek had less relapse (18%)or MRI lesions
PRISM4 Rebif 44 ug 3/week had less burden of disease or relapse c/t 22ug or placebo
Avonex dose comparison study no diff in 22 vs 66 but ug 22x3 qweek had better response less relapse so
frequency of admin more important than higher dose.
- class I randomized clinical trial
- II prospective case control study nonrandomized
- IIIa case series
- IIIb case report
- IIIc just personal opinion
- symptomatic >70%
- symptomatic 50-69% make decision case by case
- asymptomatic >60% if pt 40-75, risk<3%, life expectancy>5 year
stent if lesion not surgically accssible, medically high risk, post radiation stenosis
cardioembolic stroke wait 2-3 days repeat ct if no bleed start warfarin po no need for heparinoverlap. Sq heparin is ok for dvt prophaxis
basilar artery stutering my benefir from ia tpa or clot retrieval
if pt on ap no contra to tPA
if pt on AC if inr less than 1.7 may do tPA
ace arb statin are good in stroke pt even if normotensiv, keep ldl low
- FIRDA seen in metabolic encephalopathy
- OIRDA is seen in kids as primary generalized epilepsy
- JME generalized multiform spikes= polyspikes and waves, fragmented, shifting laterality
- MTS TIRDA temporal intermittent rythmic delta activity
- In LGSynd interictal EEG also shows slow spike/slow activity that doesn't mean pt is in SE.
Video EEG Monitoring
indications- sz dx, sztype, presurgicl evaluation
nonepiletic- panic, depression/anxiety, psychosis, don't call pseudosz, not malingering because they have seroius psych problem.
Syncope, Movement disorders,
red flags- persistant normal eeg, paradixical response or many allergies to AEDs, psychosocial issues.
dystonic movement contralat, aphasia dominant hemisphere origin, noserubbing seen in ipsilateral temporal origin, coughing shows right temporal lateralization.
SISCOM- SPECT difference superimposed on MRI.
EEG in encephalopathy
common causes- hepatic, renal, drugs, sepsis
- diffuse slowing
- if eeg shows reactivity, Claps the hand if any eeg change better prognosis
- ddx of nonconvulsive SE
- triphasic waves, bidynchronous, initial neg largest pos component, etio in HF, RF, Hypoxia post arrest, can be initiated by painful stimuli
- Drug toxicity, fastactivity eg barb, bnzd, also can present occ as bisynchronous sharp complexes, alpha coma, spindle coma, burst suppression, ECS
- bisynchronous sharp complexes or PLEDs can be seen in CJD, Hypoxia, Herpes, Baclofen, Li, Levodopa, EEG looks like EKG
- Hypoxia can cause alpha, theta,spindle coma, BSP, ECT
- Alpha coma, alpha everywhere and nonreactive to pt stimulation, it is a thalamic spontaneous rhythm and seen in subtentorial lesions, midbrain and down.
- Spindle coma in propofol, versed and infratentorial lesion after trauma, see spindle with k complex
- burst suppression only open or close eyes in ICU or post op after anesthesia
- Myoclonus status or myoclonic status epilepticus, Subtle status.
almost dead, mudcle artifact inc the amp of myoclonus, if mucle paralyzing given amp decrease
- NCSE, more then 30 min change in MS with ictal EEG. in 2 condition Ambulatory eg CPSz status or Abscence status versus
Obtubded/Comatose pt may beNCSE or Electropheragic sz,
EEG atterns- PLEDs, BIPLEDs, Tripasic Waves
most EEG expert don't believe PLEDs need tx.
NCSE Tx- lorazepam, DPH, Pentobarbital some use Versed, Propofol
NCSE should be differentiated from prolonged postictal, scan negative
EEG Peds
The illustration shows typical centrotemporal spikes, often associated with benign rolandic epilepsy of childhood, which is manifested by clonic movements of the face and hand that often progress to a more generalized seizure.
Sylvian or Rolandic epilepsy start age 6 to teens associated c focal jerking or tingling of face or hand c progression to GTC Sz
The combination of fast activity (12-14 Hz activity) and delta slowing is most often seen as an anesthetic effect or drug overdose.
Vertex or V-waves are high voltage sharp contoured waveforms that can occur with phase reversals on a bipolar montage over the central areas.
wicket spikes, constitute a benign pattern of uncertain clinical significance, occurring predominantly in the EEG of older adults during light sleep.
The breach rhythm consists of EEG activity that is increased in amplitude and prominence recorded over the area of a skull defect. The breach rhythm is most prominent when seen over the central and temporal regions.
Normal EEG changes in neontes
- trace alternant discontinuous rhythm in quiet sllep
- vertex sharp waves not seen until 2-3 months
- Delta brushes pattern of prematurity but can be seen in normal neonate
- rhythmic ant slow waves can be seen during sleep
Intracranial EEG
Periodic spikes under 2 hz before fast rhythmic activity point to sz localization in intracranial eeg
perodic spikes last 15 sec or 3 min herald sz. you don't see them in interictal or nonelectrical activities.
the other pattern could be mixed theta and beta. you see these in neocortex sz. periodic spike is seen more in MTS.
Low voltage fast activity is the most common neocortical sz activity in intracranial monitoring.
Pediatric intracranial
- suspect dual pathology eg bil MTS or MTS plus neocortex
- extratemporal>>temporal
- substrare for epilepsy
cerebral dysgenesis
hypothalamic hamartoma

EEG No Value EEG 1
Different waves
Calibration square wave biologic
At least 20 min in adults, 1 hour in kids
for base line and then response to hvt photos and in epileptic pt during sleep
Movement artifacts
sweat artifact
60 hz artifact
eye movements
Extracerebral- pulse, electrode pop up, ekg, outside powerline
abnormal asymmetric occipital
photmyoclonic or photomyogenic response is normal noncerebral response characterized by brief repetitive muscle spikes in the frontal head regions
symetrical occipital driving is normal
general slowing if prolonged more
than1 1/2 or 2 minute is abnormal
avoid hvt in COPD,Asthma, CVA, Myomoya
EEG in infants
infantile spasm hypsarrhythmia or burst suppression
myoclonic epilepsy 3 >3 cps polyspike and wave
LGSynd 2-2.5 polyspike and wave
Spike 20-70 ms
Sharp 70-200 ms
they are associated with slowing afterward, stand out from background, stereotype, activated by sleep
Normal spike & sharp
- vertex sharp waves
- 6 Hz phantom,
- 6 and 14 Hz positive spikes
- Occipital lambda
- Wicket spikes
Focal slowing- focal structural lesion
Diffuse slowing- toxic metabolic encephalopathy, neurodegenerative process eg dementia, multifocal CVA, Headtrauma
Fast beta activity- BNZD sedation
use chloral hydrate pre EEG 25-50 mg/kg po or pr, doesn't affect EEG
Focal spike or sharp- partial sz or CPSz
Diffuse spike or sharp- generalized Sz, can not r/o secondary generalization, primary focus may not be clear

Inc EEG yeild by, sleep deprived esp for TLE, HV, PS, Repeat study or prolnged EEG, >30 min
Yeild dec by tx c barb, bnzd, vpa or other AEDs
- Partial sz present as spike/sharp or focal slowing
- disruption in the background ddx epi from normal varients, normal varients are also bilateral. (Wicket spikes = rhytmic midtemporal theta of drowsiness)
- Lambda waves like POSTs in occipital when pt scanning environment and will disappear when pt close the eye

- Muscle disease
- NMJ disorder
- Peripheral neuropathy
axonal vs demyelination
conduction block
- Brachial plexopathy
- Cervical radiculopathy

- prolonged latency
- prolonged F wave
- H reflex
- myotonic discharges
Electrode placement
For motor everywhere 7 cm x post tibial 8 cm, Radial motor is 9 cm above wrist
For sensory 14 cm for Sural nerve 10 cm
Dr. Merkey office everywhere 8 post tibial 10
In normal subjects, the maximum difference between right and left median nerve motor distal latencies (stimulating at the wrist) is 0.7 msec. The maximum difference for median sensory distal latencies is 0.5 msec. When the differences between right and left are greater than these values, one can confidently diagnose median mononeuropathy at the wrist (carpal tunnel syndrome) on the side with the longer latencies. The difference between right and left is not helpful in assessing bilateral compression. Conduction velocity between elbow and wrist is not affected in this condition.
The Martin-Gruber anastomosis produces a characteristic nerve conduction pattern of a larger median motor amplitude with proximal stimulation (compared with distal stimulation) and a significantly smaller ulnar motor amplitude with proximal stimulation (when compared with distal stimulation).
Normal values
tarsal post tibial motor 4.5 ms
median ulnar motor 3.8
median sensory 3.5
measuements above these values abnormal.
CTS esp >5 distal latency, or can check NCV across wrist and if less than 35 m/s is in favor of CTS
Amp motor upper ext 5 or 4 mv
lower ext 4 or 2 mv
Amp sensory below 10 microvolt abnormal
Amp sensory below 9 microvolt in sural abnormal
abn in UE >32 in LE >58
side to side diff abn if > 3-4 msec
abn if >35 msec or if side to side diff > 3 msec
in UE >50 m/s
in LE > 40 m/s
fibrilliations, PSW are the most reliable EMG parameters for dx of radiculopathy. another evidence of chronic denervation or HALD MUPs.
fas or inc polyphasic MUPs, For H late response not good parameter.
PSWs develops 1 week earlier than fibrilliations. needle EMG should be done 3-4 weeks after disc herniation.
Sensory nerve conduction study is the cardinal rule for differentiation plexopathy from radiculopathy.
paraspinal muscles innervated by post primary rami, limb muscles by ant primary rami. paraspinal muscles develop fib PSWs 1 week earlier c/t distal muscle. above c normal sensory NCS absolute evidence of lesion prox to DRG namely nerve root or ant horn cell.
Illiac crest L3-L4 level. 2.5 cm from midline, 2.5 cm deep. exam part uppermost in cer lumbar, downward in thorasic (DM). fib PSWs can be tested, MUPs can not be tested because paraspinal relaxation is almost impossible.
Negative EMG in radiculopathy
- acute phase
- root compression caused more demyelination than axonal loss
- sensory root compression instead of root compression, pt has more pain and paresthesia, SomatoSensory EP may be useful in such situation although has it is own caveat (overlaping dermatome)
- paraspinal muscles are normal d/t sampling errors or fasicular sparing of fibers from dorsal rami
Time course of neuropathic lesions
Acute phase- reduced recruitment in clinicaly weak muscles
1-2 w- + fib in proximal muscles, normal MUAP morphology
3-4 w- + fib in distal muscles, normal MUAP morphology
5-6 w- +fib in all muscles
Reinnervation phase- larege (amp,dur) polyphasic MUAP started from proximal to distal muscles
EMG/NCS No Value EMG in myopathy brief small amp polyphasic potentials BSAPP, in neuropahty denervation potentials fibrillation, fasiculation, sharp waves and large prolonged polyphasic motor unit potentials.
In demyelinating neuropathy greater slowing of CV C/T greater dec of CMAP in axonal neuropathy
Repetitive nerve stimulation
for NMJ disorder (presents with fatiguability, fluctuation, prox weakness, dysphagia, dysartheria, ocular palsy)mainly for MG, LEMS, Botulism
in MG ab against ach receptor
in LEMS ab against presynaptic Ca channel
Blink reflex
afferent v
efferent vii
2 response R1 main sensory nucleus v in pons ipsilateral fascial
R2 to spinal nucleus of v then both fascial nucleus
4 nucleus of v- main light touch higher in midbrain mesoenvephalic for proprioception lower spinal tract for pp temp then median and anterior motor nucleus
fascial nerve also carry proprioception of face that is why pt with Bell's palsy state numbness in face although light touch is normal.
A progressive increase in latency, duration, amplitude and area of motor and sensory nerve action potentials accompanies a physiologic decline in temperature. This is reversed by warming.
Motor conduction block, abnormal temporal dispersion, slowed conduction velocities, and prolonged late responses are the electrodiagnostic features of demyelination.
The Martin-Gruber anastomosis occurs in 15-30% of the population. It consists of a communicating branch from the median nerve to the ulnar nerve in the forearm to supply the first dorsal interosseous, adductor pollicis, and abductor digiti minimi.
The most sensitive test for myasthenia gravis is single fiber EMG of the frontalis muscle.
Electrodiagnostic characteristics of neuropathy include decreased motor unit action potential (MUAP) recruitment, increased MUAP amplitude, and fibrillation potentials with a distal to proximal gradient.
Incidence about 1 percent
half of the cases are idiopathic
movement disorders
sleep disorder
complicated migaine
breath holding spells
sel stimulting beaviour
GI disorders
pschiatri disorders
brainsem,diencephalic disorders
Surgery for epilepsy
Corpus Callosotomy
Ant Temp lobectomy rate of success is about 70%
Keppra 10 20 % behavioral probledepression
Topomax cognitive SEs dificulty c memory word findings, 1.5 % kidney stone
Zonergn not first line lss cognitive SEs Zonergan stored in Erythrocytes
Lamictal no effect on cognition , doesn't affect sonolence but actually may be stimulant.
Stevens Jonson incidence is about 0.02 % among Lamictal users.
rash producing drugs: DPH, CBZ, LAM, PB use Keppra in this situation.
Lamictal is good choice for pregnancy and elderly.strtingLamictal low dse c/t cbz, dph and vpa didn't have significant difference in s control or sz free frequency.
Lamictal good for neuropathy and maybe migraine.
rash is more common when start initial dose more than 25 or rapid titration or when added to vpa or in younger pt or previous hx of atopy
Trileptal SEs dizziness, start slowly, hyponatremia more common than tegretol
Gabitril 2 percent psychosis another unusual side effect is hypotonia
switch vpa to lam
1- inc lam to 200 mg/day
2- once at 200 mg/d gradually dec vpa to 500 m/d by 500 mg decrement weekly hold this dose for 1 week
3- dec vpa 250 mg/d and inc lam to 300 mg/d , keep on this dose for 1 week
4- dicontinue vpa and if needed clinically inc lamictal
if pt on vpa start at 12.5 mg and do 12.5 mg increment weekly or every 2 weeks.

VNS success- in 40% dec sz by 50%
TL success- 70% complete control, 20% better control, 10% failure
DC of AEDs- in 1 year stop one, in 3 year dc second one and after 5 years will decide stopping all AEDs
Both auditory and visual hallucinations, persecutory delusions, and ideas of reference are seen in both temporal lobe epilepsy (TLE) and schizophrenia. A positive family history of schizophrenia, schizoid personality, or schizotypal personality is often present in schizophrenia but usually not in TLE. Affect is better preserved in TLE than in schizophrenia.
Depression Anxiety
very common in sz pt
- avoid pb
- use activating AEDs eg lamictal, CBZ
- Buspar also for anxiety/depression didn't affect sz
- Clorazepate also good for anxiety not habituating
TCA in 50% makes sz better, in 30% no change, in 10% increase sz frequency
diference between absence and cpsz
- postictal
- automatism simple in abs, complex in cpsz
- duration 5-10 if more than 15 cpsz
- frequency abs many, cpsz 3-4/day
check for hypoglycemia, SVT, Anemia
neurological causes-
Geschwind synd
personality changes in some pt CPSz that include:
intense emotion or cognition
altered sexual state more hypo,dec libido
- Familial 50%, respond well to VPA
- life long c good cognition
- start at puberty 11-18 max around 15
- myoclonus or twitching upon awakening following sleep deprivation etoh consumption
- EEG 4-6 Hz polyspikes predominantly frontal
- ddx with hypnagogic myoclonus
- Tx
VPA 85% response
Top, Keppra
Avoid DPH, CBZ
Avoid sleep deprivation, etoh, photosensitive lights, night shifts,
driving restriction, working at heights or with heavy mashinery, supervised swimming, pregnancy counseling, FA supplement.
- VNS in refractory cases
Absence sz 1/3 get better 1/3 JME 1/3 GTC Sz
MRI findings
- lesion in temp
- MTS either smaller hippo (normally L hippo 15% smaller) or inc density in hippo
softer signs enlargement of temporal horn or whole temporal lobe is smaller
look at cochlea for symetricity
Interictal dec perfusion
Postictal inc perfusion
in 1/3 of pt this pattern is reversed.
New issues in epilepsy
prolactin need to be measured in 15 min after sz, in status it may decrease afterward.
all AEDs cause bone loss x neurontin, keppra
mechanism- inc metabolism of 1,25 dihydroxy D3 in inducing agents, inc PTH, dec GI absorption in aeds such as VPA.
Bone tx
Prevention- ca 1000-1500 mg/d + vit D 400-2000 IU
Osteopenia/Osteoporosis- ca plus 2000-4000 vit D
Osteomalacia- Ca plus 5000-15000 vit D only for four weeks only then back to preventive dose
Measure BMD
Advised pt about long term consequences and document that.
In severe cases use Bifosfonates but NOT IN CHILDREN.
When can u give a loading dose of LTG
in neonate up to one month, 15 mg/kg

better called non-epileptic sz or nonelectrical spells
about 1/3 of pt with psz have also real sz
conscious production +present in malingering - absent in factitious
unconscious production + conversion -absent in somatization (or somatiform milder)
psychiatry disorder c psz-
major dep
substance abuse
histrionic/borderline/antisocial personality
Munchasen by proxy make adult or kid dependent on them sick
Ganser's synd miss everything by one
psz about 20%, 80% female, 90% report childhood abuse or first memory after 7 or amnestic intervals
presentation to pt- good news u don't have sz. there is brain and mind these come from your mind not brain.
3 reason it is not sz
- sz last 1-2 minutes at most as it is self limiting process unless status
- pattern either partial onset then march generalization or primary GTC
- post ictal slowing confusion
The clinical and EEG findings in supplementary motor seizures are distinctive, with tonic posturing, focal symptoms in the legs, not hands, and usually preserved consciousness. The seizures are often misdiagnosed as psychogenic seizures and the EEG findings are often subtle or absent.
Sz and women
estrogens epileptogenic progestrone protective
- Cataminial sz d/t inc est few days before start of bleeding or drop in progest few days after start of bleeding
true dx need pt record 6 months hx of sz and menses
tx- extra dose of AED during vulnerable period, progestrone use Provera, depoprovera IM q 3 month, acetazolamide for 10 days (250-1000 mg/day)

Katamenios-greek word means monthly
Contraceptives and AEDs
inc metabolism, inc failure,
Gaba, vigabatrin, lamictal, keppra no effect
VPA inhibitor
at least take 50 ug estradiol should be in OCP

Sz in elderly
less aura and automatism
more prolonged postictal
frontal lobe common, more during in sleep, behavioral changes
for tx start low and go slow
depakote, neurontin cause weight gain
topomax, zonesemide cause weight loss
after surgery or infection acute phase reactants may inc free level of AEDs dec and they mag get Sz.
AEDs cause osteopenia osteoporesis in elderly
Sz syndrome
- LG MR, EEG slow spike wave, underlying genetic, structural, metabolic problem, diffuse brain hypoxia, CNS infection, atonic attack, myoclonus, GTC
Tx- VPA, LTG, TPM, ZNS, VNS, Ketogenic diet, avoiding sedating drug and polypharmacy, helmet, metabolic w/u
Infantile spasm
usuall first 2 year 3-9 month
cluster of spasm c hypsarrythmia
- ACTH cause remission in 60-75%
- etio malformation eg lissencephaly, cns infection, perinatal hypoxia, cryptogenic West synd
treatable cause- b6 sz, biotin serum, folinic acid in serum, glucose transport defect (CSF glucose low, tx with ketogenic diet)
surgical tx for focal brain malformation, tuber lesion, perinatal stroke ischemic change or developmental tumor eg gangliocytoma that can be remived by surgery.
esp if EEG shows focality.
why not tx sz
- idiosyncratic reaction
- cognitive se
- birth defect
- osteoporesis
- drug interaction
- economic implication
is this sz or epilepsy
- previous history maynot be recognized
- hx ofepisodic aberrant behavior
- metabolic causes glu, lytes, ca, sepsis, rf, lf, res failure, b6
- genetic predisposition
evaluation of first sz
Oral/fascial injury
Floppy infant
Stiff adults
NE (confusion, craniofascial asymmetry, hemiatrophy)
EEG, CT Scan
Whom to tx
- known Etio
- partial
- FHx
- abn NE, EEG, MRI
Epilepsy therapy pearls Uremia
uremia inc unbound fraction of phenytoin, also pt tend to have low serum alb. Target level for 5-10 mg/dl
corr dph= dph reported/ (0.1 alb+0.1)
only 2-4% of dph removed by hemodialysis so no supplemental dose is necessary.
dph is 90% alb bound reported level is bound and free. It should be adjusted when alb is low
corr dph= dph reported/ (0.2 alb+0.1)
Equation to inc subthera level
0.7 x IBW x (15-current level)
measure dph level 2h and 2days after loading
Diamox sequels 500 mg bid or 750 bid everyday is good for cataminal epilepsy.
Sequels is long acting slow release formulation.
Extra dose of keppra at qhs to help sleep.
Take vit d and ca with all aeds esp pb dph and tegretol. Also take mv qd.
- Taper dph by 100 mg q2week to stop on 4/16/04
- stop driving when dose gets down to 200 mg qd
- may resume driving on 6/1/04 if no sz (after 2 months off the aed if sz free)
Epilepsy Treatment Drugs that can raise carbamazepine levels include isoniazid, erythromycin, cimetidine, calcium channel blockers (such as verapamil), and propoxyphene. Carbamazepine levels are lowered by phenobarbital, phenytoin, and primidone. Warfarin, chlorpromazine, digoxin, and gabapentin have no significant effect on carbamazepine levels.
Fetal vitamin K deficiency with hemorrhagic complications occurs in 10% of neonates born from mothers receiving antiepileptic drugs that induce liver metabolism of vitamin K, including phenobarbital and phenytoin. Women taking enzyme-inducing antiepileptic drugs should be treated with vitamin K1, 10-20 mg daily during the last month of pregnancy. Infants should receive 1 mg intramuscularly at birth and, if needed, fresh frozen plasma.
Foldvary N. Treatment issues for women with epilepsy. Neurol Clin 2001;19:409-425.
for CPSz tegretol unless eeg shows a generalized pattern
start at dose 10 mg/kg/day inc at weekly interval to a dosage of 15-20 mg/kg/day.
potential ADR and Sz first aid, Sz precaution discussed.
in 3-4 week CBC, CMP Na LFTs and Tegretol level should be checked.
A majority of epileptics experience significant depression at some time during the course of the disease. The suicide rate is over five times higher in epileptics than in the population as a whole.
Topiramate and zonisamide are weak inhibitors of the carbonic anhydrase, and therefore may increase urinary pH and decrease urinary citrate excretion. Both effects may predispose to kidney stones. In addition, both drugs have been associated with impaired concentration and memory, and could potentially affect school performance.
Idiosyncratic toxic reactions to valproic acid include thrombocytopenia, hepatotoxicity and pancreatitis.
Epilepsy Treatment Efficacy stat measurement of sz reduction
Effectiveness- clinical reduction of sz and toxicity, tolerability and so on.
Oxacarbamezine is not enz inducer x in 3A4 isoenz that cause failure of OCP while on this drug.
Enz inducer dph, pb, cbz, oxa
non inducer top, lam, gab, kep
enz inhib vpa
weight + 0 -
vpa,cbz,gab lam,kep,dph top,zon,fel
AEDs my inc vit D met, dec Ca abs, inc bone turnover
Bone density measurement rec for pt c chronic AEDs
malformation happen in 2-3% of general population twice in epileptic populations
choice in pregnancy lamictal, cbz
choice in elderly lamictal, neurontin
if quick load dph, vpa
lam agitation edgy
gab somnolence
top memory problem
pb sedation or hyperactivity
tachyphylaxis most seen c keprra less c lam zonisomide
Levetiracetam does not have a clinically significant effect on liver enzymes and is inactivated to a a small extent by the liver. It is mostly eliminated unchanged by the kidneys. Valproate inhibits the metabolism of other anticonvulsants, including lamotrigine and the epoxide metabolite of carbamazepine. Tiagabine has been reported to produce non-convulsive status epilepticus and absence seizures. Hyponatremia, ranging from asymptomatic to hyponatremic coma, may occur during oxcarbazepine use, particularly in the elderly. Urinary tract calculi may occur in patients while taking zonisamide (4%) or topiramate (1.5%). Weight loss with or without diminished appetite is more likely to occur with felbamate or topiramate.
Falls in elderly
Falls in the elderly 1
Acute- Stroke,TIA, Syncope, Sz
Chronic- OH (autonomic neuropathy), Meds, Visual problem (inf quadroanopsia esp.), Gait/postural instability in parki,
Ataxia, Vertigo, Gait apraxia in bil strokes/dementia, Hydrocephalus (magnetic gait, urinary incontinence, dementia), Poor proprioception B12 def, muscoloskeletal, fixed cardiac output synd (vasodilation in muscles) or pt with emphysema, anemia, otherwise it is idiopathic fall of elderly
Falls are the leading cause of both nonfatal injuries and unintentional injury deaths among older people in the United States. More than half of people age 65 or older fall each year, and 10% of these falls result in serious injury. Injuries from falls include hip fracture, other fractures, subdural hematoma, and other head injury.
Factors that increase the risk of falling:
• Depression
• Confusion
• Alzheimer's disease, or other dementia
• Impaired vision
• Impaired hearing
• Arthritis
• Weakness
• Neuropathy
• Parkinson's disease
• Impaired balance and gait
• Acute illness
• Recent hospitalization
• Multiple medications
• Specific medications
Falling is one of the most common problems associated with medications. Some medications are particularly likely to increase the risk of falling:
• Antidepressants (especially tricyclics and serotonin-reuptake inhibitors)
• Anxiolytics (especially benzodiazepines)
• Antipsychotics (especially haloperidol and phenothiazines)
• Antihypertensives
• Antiarrythmics
• Anticonvulsants
Many elderly people have multiple medical problems for which they are receiving medications. The risk of falling and confusion increases with increasing number of medications, independent of the types of medications.
At least on a yearly basis, medical care providers should ask elderly patients about any falls or difficulty with balance and gait. They should also observe their patients while rising from a chair, while standing, and while walking.
Falls in elderly Treatment Falls in the elderly 2
Any elderly patients who have observed difficulty with getting around should be considered for professionally supervised balance, gait, and muscle-strengthening programs. Such programs, coordinated by physical, occupational, or kinesio-therapists, can decrease the risk of falls by 10%.
For any patients who are falling, providers should also
• Review all medications (including over-the-counter medications)
• Eliminate problematic medications (if possible)
• Decrease the total number of medications to 4 or fewer (if possible)
• Assess for orthostatic hypotension
• Assess vision, hearing, heart, lungs, joints, muscles, and sensory function
• Obtain appropriate blood tests (including complete blood count, serum electrolytes, blood urea nitrogen, creatinine, glucose, vitamin B12 level, and thyroid stimulating hormone level).
• Obtain neuroimaging if there is a head injury, if there are new focal findings, or if there is a suspected central nervous system process based on history or examination.
• Consider tests for osteoporosis, particularly in postmenopausal women or those at increased risk of osteoporosis for other reasons (eg, steroids, cigarette smoking)
• Refer to physical therapy for comprehensive evaluation and rehabilitation
• Refer to occupational therapy for an inhome safety evaluation
• Recommend hip protectors, which decrease the risk of hip fracture by more than 50% (Lauritzen et al 1993; Ekman et al 1997).
Elimination of home hazards can result in a 20% decrease in risk of falling. Some of the changes that can decrease falling include:
• Removal of rugs
• Change to safer footwear (eg, soft, flat-soled shoes)
• Use of nonslip bathmats
• Improvement of lighting (including use of a night light)
• Addition of stair, bathtub, and toilet rails
• Removal of low chairs
• Repair of pavement irregularities
Headache Migraine
Cluster HA
Whitdrawal/Rebound HA
HA and pregnancy
Psuedotumot cerebri
Convergence Hypothesis: Migraine is a neurological process and a headache is just one symptoms that evolves from that process. A variety of different clinical presentation of ha may emerge from the migraine process including: Prodrome, Aura, Mild HA, Moderate to severe HA and actual migraine.
Tension can evolve to migraine and migraine resolve into tension.
Triggers: Internal Hormonal changes, Stress, Sleep habit changes External Weather chnages, Etoh, Glare/flickering light
Prodrome: mood disruption, sensory disruption, constititutional chnages, cognitive changes, food craving, muscle tension, nasal stuffiness/drainage, yawning may precede migraine by 1-2 days
Aura: Focal and reversible neurological symptoms, typically visual but maybe sensory, generally less than 90 mi, usually preceded ha but may occut with or during ha, does not invariably led to ha (acephalgic migraine), primary mechanism is (spreading) cortical depression
Mild/Mod HA:d/t trigeminal system inhibition: generally begins with qualities of tension type ha (dull, nonthrobbing, poorly localized,+/- muscle tenderness) last min to hours and has highest efficacy for treatment
Mod/Severe HA=Migrainous: disinhibition spread from trigeminal to central level (cortical sentization) and migraine became allodynic pain state and abortive treatment difficult. Tx should start before central sensitization occurs
IHS criteria for dx of migraine:
duration 4 to 72 hours
Pain (2 of 4): Unilat, throbbing, mod to severe, aggravated with activity
Plus (1 of 2): NV, P/P
No evidence of organic disease
Headache Migraine
Why convergence hypothesis is important? It explains clinical vaiability of ha pattern, inc our dx sensitivity to migraine, permits optimal tx
Prodrome, Aura-Acephalgic=Electrical, Tesnsion(siunus, trigeminal disinhibition, Mild/Mod ha), Migrainous(mod/sev ha, neurovascular inflammation), IHS migraine, Intractable HA (central
muscle+vascular= migraine w/ tension features
sinus+vascular= migraine w/ sinus features
Migraine tx:
Abortive tx:
Antiemetics: Dopamine receptor blocker
NSAIDs: PGE1 blocker and raise sensory threshold of trigeminal afferent
Opioids: inc central threshold for pain reception
Ergot: eg DHE serotonin agonist
Misc.: Midrin 2cap at onset can repeat 1 cap qh max 5 cap/12h
Triptans: Selective 5-HT 1B agonist (prevent vasodilation) 1D agonist activity (prevent inflammatory peptide release peripherally from trigeminal nerve, inhibition of central pain transmission by the trigeminal nucleus caudalis)
Sumatriptan has shot
Oral: 25, 50, 100 mg
Nasal: 5, 20 mg
Autoinjector: 6 mg
Rizatriptan highest efficacy
Oral: 5, 10 mg
ODT (oral disintegrating tablet) 5, 10 mg
Oral: 2.5 5 mg
ODT 2.5 5 mg
Oral 1, 2.5 mg
Frovatriptan long acting especially good for cataminal migraine mesntruall associated migraine
Oral 2.5 mg, faster acting
Triptans in practice:
- Oral meds do work at any time but they work better earlier in the migraine process
- ODTs are convenient in some settings but they are absorbed in the GI system - Nasal spray can help children and patients with nausea but taste can be a limitation
- Injection is highly effective but usually reserved for rapid onset ha and for rescue if oral tx fails
- We have to try 3 different triptans (after an adequate trial) before we call it triptan resistant
- Use can use another oral tablet after 2 hours with max of 2 times in a day and not to use it everyday
- Give pt 3 d
Headache Migraine
- Efficacy can be augmented by combination with another agent (with a different mechanism)
Triptan + NSAIDs or Triptan + Antidopmainergics
- Recurrence of ha (same ha returning before 24 hours) can be reduced by achieving pain-free response.

Rescue therapy for severe intractable migraine (d/t central sensitization):
- SQ Sumatriptan 6 mg
- DHE IM/IV 0.5 or 1 mg or Raskin protocol
- Phenothiazines eg procholperazine 10 mg IV/IM or 25 mg PR
- Valproate Na IV Depacon 500 mg
over 5 minutes
- Narcotics eg Demerol
- Mg IV 1000 mg in Normal Saline iv slowly minimum should take 30 min
- Occipital nerve blocks

Post HA treatment:
- Make sure we have right preventive treatment
- Treat similar to prodrome: Rest, Fluids, NSAIDs
Headache Migraine
which triptan
Ergot extract of rye fongus
trigeminalnerve 5HT1D on nerve ending 5HT1B on vascular artery
pain sensation inartery goes trigeminalnerve and then to trigeminal nucleus caudalis,sensory relay center and then cortex.
dopamine accelerator serotonin brake for migraine. most triptans similar structure to seretonin.
triptan D antagonist B agonist on vascular wall, causing vasoconstriction that's why they get CAD, contraindicated in CAD, over 40 get EKG, some may have esophageal spasm or dysphagia or neck pain
Fastest RT, ST ZT ET
Less Recurrence NT FT ET
sumatriptan may not be used in Sulfa allergy
triptan c SSRI may cause serotonin syndromes.

Headache Migraine
Cataminial migraine
metoprolol 50 mg bid 5 days before last day of period
naprosyn 500 mg po bid prn HA
compazine 5 mg po tid prn NV
drop in estrogen cause Migraine
Estradiol 0.05 mg qd or
Estroderm TTS 50 mcg to change twice a week
Should take one day before HA onset (usually 3-4 days before mense ) up to 3 days after start of bleeding.
Frova 2.5 qd or bid for 6 days
transcutaneus estradiol 100 to 150 ug qod for 6 days
naratriptan 1 mg bid for 6 days with supplemental 2.5 mg for breakthrough pain
Headache Migraine
Chronic daily headache CDH
>15 days and >4 hours/day untreated
prevalence about 4%
4 forms- transformed migraine, chronic tension ha, new daily persistant ha, hemicrania continua
often associated with analgesic abuse.
simple analgesic, ergotamine compounds, opioids, triptans
Headache Migraine
Cluster HA Abortive tx
High efficacy
- O2 7-10 lit/min for 15 minutes
- Imitrex SQ 6 mg
- IV/IM/SQ dihydroergotamine mesylate 0.5-1 mg
Limited efficacy
- Zolmitriptan 5-10 mg PO
- Ergotamine 1-2 mg PO or PRectal
- intranasal lidocaine

- Triptans eg Imitrex, Zomig, Ergots, migranal
- Lidocaine intranasal
- Capsaicine
- Stetoids/lidocaine blockade of greater occipital nerve
- Radiofrequency or glycerol rhizotomy
- Gamma knife of Gaserian ganglion
- Microvascular decompression
Headache Migraine
Cluster HA
why many cluster HA patients have Homers syndrome. It may be d/t some cavernous carotid arterial changes with compression of sympathetic fibers. Alternatively, since the generator for cluster HA may be in the hypothalamus, the lesion in the sympathetic system may be at the first order neuron.
How you treat this patient?
Cluster HA should be treated as an emergency since the pain is so severe as to lead some patients to suicide. Prednisone 60-80 mg daily for several days with tapering over the next week is a very effective treatment. As HAs may return after lowering the prednisone dosage, many will add a prophylactic meds such as verapamil or lithium until the HA cycle is clearly at an end.
Acute treatment of cluster HAs is difficult because since absorption of analgesic medication is often too slow. Oxygen inhalation with a facemask at approximately 8 liters/mm is often dramatically effective. Injectable sumatriptan can be very effective as well.
- cluster can be 6-8 w
- eaely morning REM sleep trigger CHA, 1-3 epiosode/day, last 1-3 h, onset vey quick and stops suddenly diff from migraine, they have to move, more supraorbital, temporal
- suicide HA, it is spontaneous or triggered by etoh, stress, hypoxia
- autonomic activation, sympathic horner, parasympathic causing lacrimation, rhinorhea etc
- O2 up to 8 lit/min 15 min Horton HA
- Steroids Solumedrol iv and then 60 mg taper
- CaCB verapamil 240 mg sustained release qd can go up to 900 mg/day
- Ergotamine, DHE 1 mg bid contra in CAD, CVA, HTN, Ergotism (constant vasospasm ssp in limbs)
- Li carbonate esp for chronic form of cluster HA, 300 mg/d titrate weekly up to 900 mg po qd, monitor level very potential for side effects, tremor, sz, dysrhytmia, hypothyroidism
- VPA 250 mg bid can titrate up 250 q3days up to 500 mg bid
- Topomax 50-150 mg/day max 200 bid
- Neurontin 900 mg/day
- Naratriptan like Frova is long acting can be used for prophylaxis in this case.
Headache Migraine
DDx of short lasting HA
Or Trigeminal-Autonomic Cephalgias
- cluster ha 15-180 min
- paroxysmal hemicrania 2-45 min
(can change to hemicrania continua)
- hypnic ha 15-30 min
- SUNCT 5-240 seconds
- idiopathic stabbing ha <30 sec
- trigeminal neuralgia <1 sec
- cluster ha orbital
- paroxysmal hemicrania orbital
- hypnic ha generalized
- SUNCT orbital
- idiopathic stabbing ha anywhere
- trigeminal neuralgia v2-v3
every type of ha more common in f x cluster, SUNCT and hypnic HA
- cluster ha etoh, nitrates
- paroxysmal hemicrania etoh, nitrates
- hypnic ha sleep in elderly
- SUNCT cutaneous
- idiopathic stabbing ha none
- trigeminal neuralgia cotaneous
- cluster ha o2-verapamil
- paroxysmal hemicrania indocin
- hypnic ha Li200-600 qhs, Verapamil 160 mg qhs, indocin
- SUNCT can try everything triptans, tegretol, baclofen, verapamil, steroids, Li, Elavil etc x indocin, lamictal, neurontin and topomax recently were efficacious.
- idiopathic stabbing ha indocin
- trigeminal neuralgia <1 sec

DDx- trigeminal neuralgia vs idiopathic stabbing ha
DDx- ha with autonomic activation- Cluster ha, Paroxysmal hemicrania ,SUNCT
Headache Migraine
- Obstructive or non communicating in Foramen of Monro, Third V, Aqueduct of Sylvius, 4th v, Foramina of Luschka and Formen of Magendie
- Commuinicating HCP
- HCP ex Vacuo
- Head trauma or birth trauma
- Meningoncephalitis, esp basilar meningitis syphilis, TB, Sarcoidosis
- Occult brain tumors
- Genetic x linked or sec to Dady Walker, ACM, Congenital abscence of archnoid villi (difficult to confirm)
- Mass lesion archnoid cyst of post fossa or any SOL in cereberum or cerebellum
Commuinicating HCP specific etiologies
- Oversecretion chroid plexus papilloma CSF>1cc/min normal is about 1/3 cc/min or 500 cc/day
- Impaired venus return lat sinus thrombosis in Otitic HCP
- Impaired absorption: Congenital abscence of archnoid villi, CSF hyperviscosity Pr>500 mg/dl (Polyneurtis or spinal cord tumors)
S & S:
- in kids skull enlargement, imapaired upward or lat gaze, exophthalmus, sluggish pupillary reaction, abcense of visual fixation or response to visual threat, Sz
- in adults HA, Papilledema, 4 or 6th palsy, Lethargy
Ataxia or weakness, Sz less common
- in Olds dementia, magnetic gait or retropulsed posture, urinary incontinence
- US, CT, MRI (inc perivent signal in T2)
- MRI with cineflow also good for ACMalformation
- or Cisternogram or Post LP improvement in walking memory in NPH (eg check opening closing pressure, large volume tap 30 cc at least)
danger- if acute HCP check ICP monitor before doing LP
while on ICP monitor need to be on Ancep 1 gram q 8h and max of 5 days can be with ICP monitor or EVD.

(Pseudotumor cause small ventricles or slit like ventricles)
Can be arrested HCP
in Kids 15% risk of Mental retardation and Sz
(Ventriculoperitoneal or pleural)
(risk of infection especially first few weeks of Shunt placements or shunt failure, disconection or Sz)
Headache Migraine
low CSF pressure HA and intracranial hypotension
- spontanous leak, dura tear
- post LP, dx, anesthesia
- postoperative craniotomy or spinal surgery
- postraumatic csf rhinorrhea, dural tear, nerve root avulsion, occult pitutary tumor
- systemic illness eg dehydration, dm coma, hyperpnea, uremia, sepsis
- dec opening pressure (<7 cm)
- csf pleocytosis, mild inc pr
- meningial enhancement in MRI
- less common enlarged sella, slit ventricles, tight basilar cisterns, engorged venus sinuses, crowding of post fossa, descent of cerebellar tonsils mimicking ACMalformation (sagging brain)
- Radioisotope nuclear scan, cisternogram
- bed rest, abdominal binders
- caffeine, theophylline
- Epidural interventions (blood patch, NaCl, Dextran patch, Fibrin glue, morphine sulfate)
- Surgical repair of leak
Headache Migraine
migraine and epilepsy linked b/o
- both familial, paroxysmal and associated c transient neuro disturbances
- incidence of epilepsy inc in migraine sufferers and vice versa
- ha can be sz manifestation
- abn EEG common in both
like basilar migraine and benign occipital epilepsy both have ha, sz epileptiform discharge
Headache Migraine
Post LP HA
positional, but if CSF pressure very low they may HA all the time.
- Lumbar blood patch
- MRI of cervical spine c cineflow
- Caffeine benzoate 500 mg/1 lit NS TRO 6h not later after 6 pm
- strong coffee not later after 6 pm
- lay flat to minimize symptoms
Headache Migraine
Pseudotumor cerebri 1
idiopathic intracranial HTN
worsen during pregnancy but healthy baby
usually develop after 14 w disappear after 1-3 months, obese or gain weight during pregnancy
- check VF, VA, BSpot
- check MRV and if abn Angio eg L transvers sinus thrombosis then pt need 3-6 m AC and repeat studies.
- if CSF>35 is severe
- moderation in diet to prevent weight gain
- if vision loss prednisone or dexa x 2 weeks
- 4-6 LP can be done sometimes weekly before considering optic nerve fenestration or lumboperitoneal shunt
- Acetazolomide 250 mg qd or bid start and inc by 250 mg qw to max 500 bid , should start after20w gestation
- Lortab or Tylenol3
- pain control during delivery to dec acute rise in CSF pressure
- pt c pseudotumor frequently have migraine but can diff it, that's my pressure HA, the other my episodic migraine HA
- obesity
- ID eg OM, Mastoiditis, sinusitis, varicella
- head trauma
- inc vit A, or other fat soluable vitamins
- Cystic fbrosis
- poisoning eg herbicides, insectisides
- dec PTH
- dural venus thrombosis (chicken or egg story)
- R heart failure
- APL synd, SLE, Sarcoidosis
abx tetr, mino, genta, pcn, nalidixic acid, ofloxacin, nitrofurantoin, SMX
OCP oral, implant
CSs use or withdrawal triamcinolone
Thyroid hormones
IS eg cyclosporin
NSAIDs ketoprofen, Indocin
Others Amiodarone, Li, NTG, Sinemet, Bromide, Fentanyl, Halothane, rGH, Provera
rest LP csf>25 cm h2o
- meningoencephalitis
- venus sinus thrombosiscerebral abcess or SOL
- Optic neuritis
- Lyme disease
- migraine
Headache Migraine
pseudotumor cerebri 2
- check VF, VA, enlarged BSpot if abn ophthalmology consult
- check MRV and if abn Angio eg L transvers sinus thrombosis then pt need 3-6 m AC and repeat studies.
- if CSF>35 is severe
- moderation in diet to prevent weight gain, promote weight loss
- if vision loss prednisone or dexa x 2 weeks
pred A 40-60mg/d C1-2mg/kg/d qd
dexa A 4mg po q6h C 0.25-0.5 mg/kg/d in 2-4 divided dose
- 4-6 LP can be done sometimes weekly before considering optic nerve fenestration or lumboperitoneal shunt
- Acetazolomide 250 mg qd or bid start and inc by 250 mg qw to max 500 bid , should start after20w gestation
A 250-1500/d
C 10mg/kg/d
- Topomax, Depakote
- Lasix A 20-80 mg/d C 1mg/kg/d
- Manitol 1-2 g/kg/ IV over10-20 minutes then 0.25 g/kg q6-8h
- Lortab or Tylenol3
- pain control during delivery to dec acute rise in CSF pressure
- pt c pseudotumor frequently have migraine but can diff it, that's my pressure HA, the other my episodic migraine HA
Headache Migraine
Status migrianosous
severe migraine with total disability lasting > 3 days
migraine could be intermittent, chronic, status migranosous
- Raskin
- IV Depacon 250 over 5 min or 500 over half hour max 750-1000/day
- Droperidol 1 mg IV
- Thorazine 25-50 mg IV watch hypotension
Intravenous fluids and electrolyte replacement as indicated
Sumatriptan 6 mg SC
Intractable migraine may respond to metoclopromide 10 mg IV and DHE 0.5 mg to 1.0 mg (depending upon response) IV every 8 hours for 2 to 3 days as indicated. DHE and triptans should not be used within 24 hours of each other.
Prochlorperazine 5 to 10 mg IV
Ketorolac 30 to 60 mg IM
Corticosteroids (single or rapidly tapering dose of prednisone starting at 80 mg a day or dexamethasone 6 mg PO or IV)
Parenteral narcotics such as meperidine with promethazine
Valproate sodium 500 mg diluted in 50 ml of saline administered IV over 5 to 10 minutes: can be repeated every 8 hours for 2 days
Droperidol (2.5 mg IM or IV)
Magnesium sulfate 1 g IV over 15 minutes
Headache Migraine
Trigeminal neuroalgia
cluster HA, SUNCT, paroxysmal hemicrania, MS, dolichoectasia of BA, tumors
NCS impaired blink reflex
mostly primary idiopathic
secondary- MS, Vascular compression, tumors(shwanoma,ependymoma), trauma, dental procedures, infectious Zooster
MRI of brain c 5th nerve focus
LP if suspect MS
ORL/Dental consult
NCS Blink reflex
*carbamazepine titrate slowly b/o autoinduction 400-1200 mg/d
check for cbc na lfts
SE ataxia, diplopia, NV, sedation
second line in intractable causes
more hyponatremia and OCP failure
*Baclofen 10-30 tid taper b/o risk of sz
*phenytoin variable efficacy
*Lamictal promising
*Lidocaine patch
*Surgery- risk corneal ulcer anesthesia, anesthesia delarosa, jaw weakness
-Etoh, glycerin injection,
-microvascular decomp Jannetta procedure displace artery by Teflon cushion or glue to somewhere else complication contralateral paresis cerebellar injury, chemical meningitis, 5 or 7 paresis same side (pre op BAER).
-Gamma knife 60-70% good result in 5 years
Glossopharyngeal neuralgia- lancinating throat pain that radiate to tongue, tx c CBZ,DPH, microvascular decompression or nerve root section
Amebic infections
- Acanthamoeba fresh water, granulomatous encephalitis in immunodef
- Entamoeba hep brain abscess in immunocom
- Negleria fresh water in swimmer fulminant mencephalitis
- Plasmodium and Trypanosoma produce me s abscess
Aseptic meningitis
- d/t meds NSAIDs, AEDs, Sulfa
- d/t CVD eg SLE
- mild viral meningitis
The CSF findings of pressure elevation, hypoglycorrhachia, mildly elevated protein, and mononuclear pleocytosis are most consistent with chronic meningitis due to fungi or mycobacteria. The reduced glucose is especially helpful in distinguishing viral infections such as herpes encephalitis and progressive multifocal leukoencephalopathy from chronic fungal or tuberculous meningitis.
high pr no cell- GBS, Froyn synd Spinal block, DM, recovering stage of GBS, very old age
>100 pr not old age
high pr and cells in polio, HIV
Oligoclonal band- SSPE, Sarcoidosis, neurodyphilis, MS, ADEM
- Check for Herpes PCR (if first lp neg second week repeat lp)
- Serum IgM, Ig G for Herpes, CMV, EBV
- West nile virus
- HIV, Enterovirus, Echo, Coxsacki, arbovirus
- California, St. Luis, Western/Eastern equine virus
- Rubella, Rubeola
- Tick panel (Borrelia, Ricketsia, Ehrlichia)
- Syphilis
- Leptospirosis
neurosyphilis 4 forms
general paresis of insane
tabes dorsalis
cranial neuropathy, basilar meningitis
RPR reactive
FTA reactive titer
VDRL and RPR with tx decrease or even s tx become negative eventually. RPR been used to check response to treatment.
MHA and FTA remain high even after treatment.
CSF VDRL positive worthy neg does not r/o it, esp if pt have high pr and lymphocytosis
CSF FTA neg worthy may became false positive upon blood contamination
Tx PCN G 4 million unit q4h for 3-5 weeks
False positive RPR - CVD, Pregnancy, old ages, drug addiction, pt vaccinated against hep B or influenza or other numerous nonsyphilitic infectious inflammatory states
Prion disease
80-90% sporadic, familial, iatrogenic, vCJD
Prion syndromes
- Kuru Guaina
- GGS familial ataxia, <55, late dementia, amyloid plaque
- FFI familial fatal insomnia, gliosis, <55
- CJD transplant
- vCJD from BSE
not activated by formalin so neuropath specimen or surfaces should be cleaned by 1-2 N NaOH or high degree autoclav
probable- pro dementia<2, myoclonus, ataxia, pyramidal/extrapyramidal/psychiatric/painful sensory symptoms AND EEG change
sl (60% sensitivity), Pr 14-3-3 in CSF
possible- abscence of EEG changes
Infection Infection Tuberculosis CNS
even 1-5 bacteria deposited in alveoli can cause infection.
primary infection asymptomatic or nonspecific pneumonitis
then become dormant and then reactivated somewhere in body including CNS.
Miliary is hematogenous spread that all lesions same age synchronously.
CNS TB case fatality rate 15-40%
- Meningitis
- Tuberculoma
- Archnoiditis in spinal cord
HIV inc the risk 3 times
one in 3 HIV pt may have mycobacterial infection
- cerebral edema, periventricular edema in PD
- Tuberculoma
- Basilar meningial enhancement
- Cold abcess epidural abcess with destruction of bones
- HCP is very common complication
PPD, AFB Smear not very sensitive
PCR, ELISA , Adenosin deaminase
Serial LP QD for 3 days and send for Zeil-Nilson stain, if lymphocytosis and clinical suspicious start tx
6 months regimn
4 months IREP 2 months IR
- Steroids dec inflammatory response, dec ICP
Dexamethasone for inc ICP

Infection Y Cysti cercosis
eating undercooked pork cause tapeworm infection which is diferent from neurocysticercosis caused by eating ova.
82% paranchymal
15% meningial
3% ventricular
causing HA, HCP, Sz
- Albendazole 15 mg/kg/d for 14 days
- Dexa (for multiple cyst) 8.4 mg/day in 4 divided dose for 7 days
- Dilantin for sz for 2 years or cysts gone
- Repeat neuroimaging in 2 years
Tx of meningial or ventricular forms
- CSF shunt for HCP
- Albendazole and Steroids for years
- Cyst removal of cysts if possible
- Avoid eating ova ( through raw veg, fruits, handshake) risk for occ visitors maybe low
- Stool ova and parasite should be checked in entire family
if tapeworm found Praziquantol 20 mg/kg once for all family member
- Cook or freeze (-20 degree) all pork to prevent tapeworm infection
- As high as 15% of mexican worker or farmer may have tapeworm infection.
Movement disorders
Basal Ganglia Disorders
gp i and gp e although close to each fx different.
BG outflow is GPi SNc
everywhere gaba x STN glutamate that cause hemibalismus.
glutamate is bad for body b/o neurodamage
in PD direct circuit underactive indirect hyperactive
GPi destruction for tremor dyskinesia or high frequency DBS (inc refractory peroid ofneurons)
then better option would be DBS in STN
STN better than GPi for DBS
MPP + inhibit on complex I of mitochondria
Rotenone organic pesticide obtained from tree can act similar
dementia puligistica and post encephalitis pd and psp don't have lewy body only tangles
lewybody in pd (x pd d/t parkin gene)and lewy body dementia.
The subthalamic nucleus modulates (suppresses) ispilateral basal ganglionic activity, which in turn modulates cortical motor outflow to the contralateral effector muscles. In general, basal ganglionic lesions have contralateral motoric effects. In the case of the subthalamic nucleus, contralateral hemiballismus – high amplitude flinging appendicular movements – ensues. A right subthalamic infarct leads to left sided hemiballismus. STN of luys infarct usually d/t stroke
methanol cause bil hemorrhagic necrosis of lat. putamen and claustrum. CO cause bil hemorrhagic necrosis of GP.
Movement disorders
Botox injection
Each bottle has 100 unit to mix with 1.1 cc solvent NaCl 0.9%
ipsilateral splenius capitus 40-60 U
contralat SCM 50-60 U inject higher up, lower injection cause dysphagia
Levator scapulae 15 u
Trapezius 15 u
5-5-5 in 3 lateral around eye
1.25 in lat. upper lid

Hemifascial spasm
- upper lid med and lat 2.5
- lower lid lat 2.5
- canthus 2.5
- zygomatic 2.5
adduc shoulder pec 25 25
elbow flex brachialis not biceps since it is also secondary supinator
wrist flex fcu fcr fdp fds
thumb in oppenens

Gebauer ethyl chloride
Teca Sapphire 2
flex toes
flexor mid sole 50 u
flexor halu longus 50
gm solus gas pass the knee soleus does not
extensor hall for hitch hiker toe
few cm above maleus in front and middle
writer cramp 5 10 u
eip opp fcr fdp fds
rectus abdominis
spine retus 200 paraspinal 100 each side
20-30 u 1 cm below targus and ear
atropin scopolamine patch glycopyrolaate
subligual usee if atropin
benzotropin trihexiphenidyl

each myobloc 50 equal 1 unit Botox
ambu needle are better for skin preparation
Movement disorders
Botox Sialorrhea
20-30 u 1 cm below targus and ear
atropin scopolamine patch glycopyrolaate
subligual usee if atropin
benzotropin trihexiphenidyl
radiation and surgical removal
you have to inject both
parotid gland secretion more with food
submandibular at rest
parotid 5-75 SM 5-30 u
1000 250 myobloc
pt 2500 myobloc each parotid
250 each SM
depth of gland 5.2- 5.3 mm
not more than 8 mm deep
parotid 12.5 SM 12.5 each side
parotid 2 injections SM 1 injec
half way between corner of mouth to targus toward ear 2 injections
SM half way between mentalis and mandible angle 1 cm inside
Myobloc has more selectivity for parasympathic innervation
myobloc for drooling
pd pt who need bont treatment
parotid secretion thicker SM serous
Movement disorders
- Gravidarum
- Drugs eg Neuroleptics
- Huntington
- Inc FT4
- Polycytemia
- Acanthocytosis
- Stroke
- MS
- Sydenham chorea
most common cause of chorea in kids
d/t group A beta hem streptococcus
ss chorea, emotional liability, dysartheria, hypotonia, OCD
dx by inc antistreptolysin O titer
dopamine depleter
Movement disorders
CAG repeat
auto dominant +FHx
Genetic test
Inderal good for impulsive behavior but inc risk of depression
Zoloft for depression
Bladder problems fre urgency Detrol or Ditropan
Movement disorders
Myoclonus 1
cortical, subcortical, reticular (gillian mallort triangle), spinal
etiologic classification
- physiologic hypnic (sleep jerk), hiccup
- c sz no encephalopathy eg epilepsy synd (Epilepsia partialis continua, JME, Lennox Gastaut, infantile spasm, photosensitive myoclonus, myoclonus absence, idiopathic)
- c static or progressive encephalopathy eg dementia (alz, cbgd, cjd), metabolic (hepatic, uremia, hyperthyroidism etc), post hypoxic/ischemic encephalopathy (lance adams)
- subcortical BD disorders, Storage disorders
- spinal cord injury, myelopathy, ataxia-telengectasia, friedrich ataxia
- idiopathic essential
- meds eg serotonin synd, TCA, DPH, PCN, Demerol/morphin, Li, L dopa
Metabolic- RF,HF astrexis
Posthypoxic/ischemic after MI arrest
Paraneoplastic ovar opsoclonus myoclonus
Spinal myoclonus eg AIDS
Myoclonus/cervical dystonia
Myoclonic epilepsy
- TSH, FT4
- MRI of brain
clonazepam 0.25-0.5-1 mg tid
Valium drip
Valproic acid
Movement disorders
Myoclonus 2
palatal myoclonus- lesion in Guillian Mollaret triangle (central tegmental tract-red nucleus, inf olivary nucleus, contralat dentate nucleus), also cause rubral tremor
- posthypoxic (Lance Adams synd)
- essential or idiopathic
- epileptic
- d/t meds eg serotonin synd, TCA,DPH, PCN, Demerol/morphin, Li, L dopa
- multiorgan failure
- Dementia Alz, CJD
- BG disorders, CGBD
- Spinal myoclonus after any spinal lesion eg SCI etc.
- remove drug or etiology
- klonopin 1 mg/day or more
- depakote for epileptic, essential, posthypoxic or myoclonus associated c Huntington
- 5 OH Tryptophan start 100 mg increment of 200 mg q3days up to 1000 mg or more 4000 mg, carbidopa 75-150 mg/day can be given to prevent extracerebral conversion of 5-OH Tryptophan to serotonin. this regimen esp good for posthypoxic or epileptic myoclonus
- anecdotally eg etoh, estrogens, tetrabenazine, artane, benztropine, botox for oculopalatal myoclonus

Movement disorders
Parkinson plus
*Lewy body dementia- visual hallucination, fluctuating MS, sensitivity to neuroleptic, resistant to L Dopa
Movement disorders
PD hallucination/psychosis
- Serequel 25 mg qhs
- dc or minimize sedatives/narcotics ativan vistril demerol....
- make sure not d/t organic causes, check cbc cmp ua dc foley
- enforce day/night cycles, during the day window open and keep pt active during dar, recreational therapy, during nights no nursing interruption
For tardive dyskinesia- can use tetrbenezin 25 mg bid up to 50 mg bid. may cause depression, is dopamin depleter.
Tardive dyskinesia
complex repetitive neck or buccolingual movement in 25 per of pt on antipsychotic or tf per who discontinue them (emergent tardive dyskinesia)

Combo tx tetrabenzaine 100-150 plus 100-200 clozapine plus 6 clonazepam
Movement disorders
- vertical gaze palsy downward>upward
- regidity axial>exteremity
- more postural instability
- less dementia, mild

Movement disorders
Pergolide start at 0.05 up to 0.25-0.75 be careful about cardiac valvular fibrosis
Mirapex better choice
Sinemet causing daytime rebound, earlier appearance of symptoms in afternoon referred to as augmentation and tolerance
Oxycodone addictive, but very effective last resort not related to analgesic effect
BNZD daytime somnolence, addictive
Gabapentin maybe helpful

Secondary RLS
- IDA check ferritin if low supplement (low CNS iron storage dec CSF ferritin inc transferin) esp if serum ferritin <50 and iron sat <16
iron not efficasious if no IDA
iron is cofactor for tyrosine hydroxylase for dopamine synthesis
- RF
- Pregnancy 3 trimester
- Neuropathy low back syndrome
- Meds
TCA, SSRI questionable, DA receptor blockers
antihistamins contrindicated in RLS
Assessment of RLS
- serum ferritin level
- Cr, Glu, B12, FA, MCV
- EMG/NCS if neuropathy suspected
- PSG sleep study
- 40 60 percent familial
- PLMD pt is not aware unlike RLS which pt is aware and give good hx
commonly in sleep with regular interval
- PN do w/u
- Akathisia generalized inner restlessness
- Muscle cramp quinin localized cramp
- Arthritis
Movement disorders
Serotonin syndrome consists of a combination of mental and behavioral changes, motor hyperactivity, and autonomic lability, that occurs following use of potent serotomimetic agents alone or in combination with non-specific monoamine oxidase inhibitors (MAOIs). This syndrome can occur in patients taking various combinations of drugs, including serotonin precursors (e.g. tryptophan), serotonin reuptake inhibitors (e.g. fluoxetine, sertraline, clomipramine, imipramine, nortriptyline, trazodone), MAOIs (clorgyline, phenelzine, tranylcypromine, iproniazid).
Bodner RA, Lynch T, Lewis L, et al. Serotonin syndrome. Neurology 1995;45:219-223.
The serotonin syndrome displays myoclonus, fever, confusion, ataxia, movement problems, sweating, and shivering. Prominent myoclonus helps differentiate it from the neuroleptic malignant syndrome.
The onset of orofacial dyskinesias with lingual and oral dystonia in a 30-year-old patient is characteristic of neuroacanthocytosis which may also be associated with chorea and peripheral polyneuropathy. ddx c whipple
- L tryptophan for sleep
- Amphetamines
- SSRI, TCA, Ectasy
- LSD, Li direct receptor stimulator
- ECT can inc S in body or S synd
- Triptans serotonin agonists but less likely to cause S syndrome.
- autonomic
- motor eg myoclonus, inc reflexes
- cognitive/behavioral eg hallucinations
- r/o infectious metabolic causes, neuroleptics should not be on board or the dose not inc recently
Labs- inc CPK, WBC, LFTs
- NMS (slower in onset, temp>38, S synd sudden onset in 24h after new drug introduction plus myoclonus)
- Overdosage sympathomimetics, anticholinergics
- DT
- Herpes infectious encephalitis
- Akathisia
- DC drug
- Klonopin
- Inderal
- Cyproheptadine 4 mg q2-4h up to 0.5 mg/kg/day
- Benadryl 50 mg IM

Movement disorders
those persists at nights
fascial hemispasm
palatal myoclonus
severe general dystonia
paroxysmal nocturnal dystonia

acute onset x hemibalimus, destractable x tic, suppressible
Movement disorders
motor, vocal or sensory tic eg itching
- Physiologic mannerisim in MR or Autism
- Idiopathis Hereditary
- Head trauma, encephalitis
- Drug induced antipsychotics, Stimulants eg Amphethamines
- Huntington
- CO or Mn poisoning
- Tourette syndrome (both motor and vocal tic present > 1year, onset before 18) associated with OCD, ADHD
- Behavioral therapy
- 1 alpha agonists eg clonidine, guanfacine
ADHD subtype clonidine+/- methylphenidate
quarter tab for 1week, half tab for 1week then quarter in am half tab in pm
- 2 Atypical AS risperidone, olanzapine
- 3 traditional Neuroleptics Haldol, pimozide
- Other eg dopamine depleters, Klonopin, Botox, SSRIs for OCD
Movement disorders
Wilson’s disease is an autosomal recessive trait associated with mutations of the copper-transporting ATPase gene on chromosome 13q14.3. Clinical features are neurological (40%), hepatic(40%), and psychiatric (15%). Patients present in the second or third decade of life. Neurologic features include an akinetic-rigid syndrome resembling parkinsonism, generalized dystonia, or postural tremor with ataxia. Dysarthria and clumsiness of the hands are common presenting features. Kayser-Fleischer rings are present in virtually all patients with neurological features. Symptoms of liver disease include a history of prior or concurrent liver disease. The pathologic abnormalities are primarily in the basal ganglia, with cavitary necrosis of the putamen and caudate, in addition to cortical atrophy. The liver develops a nodular cirrhosis.In most cases Wilson’s disease can be diagnosed by measurement of the serum concentration of the copper protein, ceruloplasmin, which is often low (<20mg/dl). Serum total copper is low in many patients and urinary copper excretion is always raised. Definitive investigation is a liver biopsy with measurement of copper concentration.D-penicillamine with pyridoxine is the gold standard of treatment. Alternative therapies include trientene, zinc, tetrathiomolybdate, dimercapol, and liver transplantation. Symptomatic treatment with antiparkinsonism drugs may be of benefit.
Bradley WG, Daroff RB. Fenichel GM, et al, editors. Neurology in clinical practice. 3rd ed. Boston: Butterworth-Heinemann, 2000.
Movement disorders ET Essential Tremor
Most common adult-onset movement disorder more common than PD
Partly genetic AD or Ch 2p and 3q
Hand tremor (difficulty writing, eating, drinking), Head bobbing, voice changes (vocal tremor) and rarely legs
Suppression by Etoh
- Meds: Lithim, valproic acid, B2 agonists, theophylin, cyclosporin
- Hyperthyroidism
- Parkinsonism: Absence of rigidity, bradykinesia or postural instability
Hand writing large macrogrphia, in parki micrographia
Head nodding, in parki movements of jaw/lip/tongue
- Cerebellar intention tremor: Absence of dysmetria,
dysdiadochokinesia and exaggeration of tremor with intention
- Physiologic tremor in mild cases
- Post CVA tremor
- Wilson (tremor c fascial dystonia, always below age 55, mri t2 signal changes in BG and dentate nucleus), Huntington disease
- Serotoninergic syndrome/reaction like SSRI myoclonic jerks
- Head tremor mostly d/t cervical dystonia, hyperthyroidism, cerebellar disorders
- B blocker e.g. Inderal up to 240 mg/day
- primidone up to 750 mg/day (not very effective in fast metabolizer b/o fast metabolization to pb, its effect d/t to p metabolite)
- pramipexole (Mirapex) 0.125 mg po bid or tid
- clonazepam (Klonopin) 0.25 or 0.5 mg po bid
- clozapine
- methazolamide
- glutethimide
- Topomax good for essential tremor 50-200 mg
- Gabapentine
- Botox injection
- In severe cases stereotactic thalamotomy to reduce tremor in contralateral limbs. or VIM ventrointermediate nucleus of thalamus stimulation or ablation
orthostatic tremor can be part of ET, tx neurontin, klonopin
Movement disorders Parkinsonism DBS
although called stimulator they put axon and neurons in refractory period.
- in VL thalamus only for tremor
- in GPi for dyskinesia
- in subthalamic for regidity, hypokinesia, best option, best efficacy
Poor candidate
- minimal response to levodopa
- dementia
- untreated depression or other psych problem
- uncontrolled htn or bleeding diathesis
- need for MRI can not have it afterward
- uncooperative during surgery or programming visits
- atypical parkinsonism

DBS not good for midline symptoms eg speech, dysphagia, postural instability
DBS good for off time and reduce dyskinesia as well
DBS reduce the need for meds by 33 percent
Movement disorders Parkinsonism drug induced parkinsonism
- anti psychotics
thioridazine mellaril
risperidone risperidal
olanzepine zyprexa
- antidepressant/antipsychotic combinations
- anti emetics
- anti histamine
promethazine phenergan
- dopamine depletors
- other
Ca CB flunarizine, cinnarizine
vincristine, 5 fluorouracil
amphotericin B
Tx- Amantadine is choice because it is AC, NMDA antagonist and also cause dopamine release.
100 mg bid, if debilitatd or taking other parkinson med start 100 mg qd then inc by 100 mg qw
usual dose 100 bid max 400/day
Sinemet doesn't work and Mirapex either because drugs eg haldol are D2 receptor blocker and Mirapex D2 agonist.
Movement disorders Parkinsonism PD Management
Dopaminergic drugs for young pt because it may neuroprotect
in elderly c MCI Ldopa
mirapex better for pt with tremor, requip better for pt c cognitive impairment you should try up to 3 mg tid to call it requip failure. requip and mirapex less retroperitoneal fibrosis, bromocriptin and permax ergot compound and risk of retroperitoneal fibrosis. also reported cardiac valve fibrosis.
for OH flurocortizone or midodrine
for REM behavior sleep disorder Klonopin
for depression/insomnia trazodone
for hallucination/psychosis
- Serequel 25 mg qhs to max 25 tid max dose 200-300/day

for drooling trihexiphenydil but caution anticholinergics in elderly b/o risk of confusuion, glucoma, constipation, boo (b o obstruction)
tx for wearing off in advanced PD
- inc freq of L dopa
- change standard L dopa to CR Sinemet
- add entacapone
- add dopamine agonist
- add amantadine
- add selegeline
tx for dyskinesia
- add amantadine
- add dopamine agonist reduce dose of L dopa
- eliminate selegeline
- eliminate entacapone
- change CR Sinemet to standard L dopa
tx of psychosis
reduce or eliminate
- amantadine
- selegeline
- anticholinergics
- dopamine agonists
Consider adding
- Serequoel 25 mg qhs
- Clozapine
tx can be started c AC, or amantadine for mild SS in young <50 pts
for mod young pts c DAgonists
for severe elderly c L dopa
new neuroprotective agents for PD tx- vit E, Coenzyme Q10, Rasageline (1-2 mg/day) or selegeline
selegeline for fatigue sleepiness
Anticholinergic for tremor
Amantadine for tremor good anticholinergic, dopamin agonist and NMDA Agonist
Sinemet for elderly pt and c cognitive deficits, if used in young people cause dyskinesia the younger you are the worse you can get
DA no interaction with dietry pr, longer half life, less risk of dyskinesia, possible neuroprotective effect, risk for sleepiness one step before narcolepsy, use sleep screening or use Provigil.

Movement disorders Parkinsonism PD Sleep problems
- insomnia
RLS BNZ,dopa, opioid, depression TCA, med SE, dyskinesia (reduce dopminergic drug or add hypnotic)
- hypersomnia ask about their night sleep, switch dopa agonist, or reduce the dose slightly.
- excessive nocturnal motor activity
- hallucinations/behavioral problems
EDSleepiness in PD
ask about their night sleep, switch dopa agonist, or reduce the dose slightly. can use caffeine, bupropion Wellbutrin, modafinil 100-200/day.
REM Behavior Disorder tx
- safety measurement
- clonazepam 0.25-0.5 mg
- melatonin 3-12 mg
- neuroleptics (Serequel)
- gabapentin works for everything x epilepsy
RBD vs Sundowning
less than 30 min >30
mostly in bed mostly wandering
appears sleepy dreaming vs awake/confused
PSG REM sleep s atonia vs awake rhythm c excessive slow activity
most RBD have Lewy body dementia or MSA not PD
- c RLS
- c Narcolepsy,OSA, MSA, LBD, PD, RBD
RLS is subcategory of PLMS
MSA they can have paradoxical movement of vocal cord and have sudden death at sleep.
Movement disorders Parkinsonism PD
genetic-alpha synuclein, parkin, tau pr ,uch-lh
park 1to 8 gene
parkin gene produce ubiquitin ligase and malfunction and accumulation of alpha synuclein
PD is a synucleopathy
dementia puligistica don't have Lewy body like MPP+ induced
parkinsonism. in dementia puligistica they have tangles like ALZ.
MPP+ cause parki through inhibition of complex I. same as Rotenone
brain stimulator use high frequency and actually destruct STN GPi good for tremor dyskinesia, VL Thalamus stimulation good for tremor only (board q)
Fetal cell transplant
Eye movement
ocular bubing in icu pt bad prognosis
in thalamic lesions
in pvegstate pt can have pursuit occipital movement saccadic eye movement in frontal eye feild
optokinetic nystagmus with strip drum they should have downward saccad in PSP they loose it
Opsuclonus myoclonus of eye

new agents fo PD tx- vit E, Coenzyme Q10, Rasageline
GPi outflow teact in BG circuitary
postinfectious demyelination can happen with or after viral illnesses and persumed to be immune mediated.
RFs- viral illnesses (measles), bacterial infection, vaccination (MMR, Rabies), inc incidence in immunocompromised pt on CT or HIV positive
Demyelination eg
Brachial or Lumbar plexopathy
transverse myelitis
acute cerebellar ataxia
optic neuritis
Bell's palsy
lethargy, weakness, HA, NV
FND, Sz, Coma at the other end of spectrum
Mortality highest in first week
CSF- inc Pr, Lymph pleocytosis
MRI wm changes r/o ADLeukodystrophy in boys
ddx c MS, polysymptomatic MS monosymptomatic, preceding illness, AEDM involve more basal ganglia thalamus as well as optic nerves, MRI lesions all enhaced c GAD same time and in MS CSF Pr close to normal.
W/U- May need to get MRI of spine
repeat LP if not get better and if severe sec ICP, tx of infection, check for herpes PCR, EBV, bartonella
Tx- CS or plasmapheresis
MP 400mg/m2 for 3 days (IV over 8 hours) then
7 days of Prednisone 2 mg/kg/day
then taper over 3-4 weeks per pt condition
If suspect infection use IVIG 1gr/kg qd for 2 days
Some may have recurrent ADEM, if >6 months then it would be MS.
Prognosis- 50-70% recovery, 10% may develop MS, Devic etc.
Postimmunization encephalopathy
3 vac type
- live attenuated (MMR, Varicella, oral polio)
- killed organism (pertusis sz, influenza, rabies EM or polyneuropathy, inactivated polio)
- toxoids (diphteria, tetanus GBS, Brachial plexitis)
- Lupus
- Sarcoid has meningial enhancement too
- B12 def
- Lymphoma corpus callosum lesion in GBM, Lymphoma, MS, Marchiava bignami
- migrain, ischemic, CADASIL
depends of cut 3 mm ideal is better than usual 10 mm
GAD should be 5-10 min time before scan
MS also involve U fibers mainly in frontal problem
memory problem d/t lesions in frontal or thalamic
for MS PD>T2>FLAIR sequences is better
brain parancymal fraction= BPV/BV
most accurate c disability and cognitive decline
mri criteria
3 of 4
one gad or more than 9 lesion
one infratentorial or spinal cord
one juxtacortical
more than 3 T2 lesions
time criteria
3 months or 30 days or anytime new T2 lesions
if more than 3 T2 lesion there is more than 80 percent chance to develop MS in 7 or 10 years
MS DDx Lyme
CSF picture
Lyme MS
WBC: Inc, L Pleocytosis Normal
Lyme Ab: +++ + in 24%
IgG index: Normal Inc
MBP: Absent Present
Oligo Band: + +

Lyme CSF in 38 patients:
WBC 166 (15-700)
Lymph93% (40-100)
Glu 49 (33-61)
Pr 79 (8-400)
IgG index 0.18 (0.44-0.9)
Oligoclonal Band Present
MBP Absent
VDRL Absent
- Vasculitis eg PAN, SLE, Primary CNS Angitis, IVDA
- HTN PVWM changes
- HIV, PML, HTLV1 test ab
- Lyme ab titer
- Meningovascular syphilis RPR
- B12 def. eg. subacute combined degeneration
- Leukodystrophy check VLCFatty acid
- Mithochondrial disorder eg Leber optic atrophy check serum CSF lactic acid, muscle biopsy, mitochon DNA analysis, MELAS, Leigh disease (subacute necrotizing encephalomyelopathy)
- SLE, APL synd check ANA, dsDNA ab or anti SM ab, Lupus anticogulant
- Sjogren LO, RI ab
- Behcet synd
- Sarcoidosis (progressive optic atrophy, Bell palsy, myelopathy)check serum CSF ACE
- CNS lymphoma
- Arnold Chiaty malformation
- Spinal tumors
- Syringomyelia
- Post fossa mass
- ADEM (less Dawson finger, less single lesion, more BG and thalamus
- Optic neuritis
- Transverse myelitis
- Devic disease (normal brain MRI, CSF cell>50, no brainstem cerebellar or cognitive dysfunction, only spinal cord plus optic nerve, devic Ab in Mayo clinic )
- Schilder disease PVWM changes also involve the U fibers
- Marburg disease is acute MS with involvement of brain stem cause death in 1 year
- Balo disease, varint of MS c concentric rings of demyelination
ENA Reichlin SSa SSb
Sarcoidosis ACE
Leber optic neuropathy
Novantrone if fail immunomodulation
check EF through MUGA scan (nuclear ventriculogram by nuclear medicine) if EF>50% then Novantrone
12 mg/m2 IV q3months
MS progression monitoring
- Clinical relapse
- MRI enhancing MRI lesion, no of lesion, volume of lesions
- EDSS Scale
During pregnancy stop all inf, copaxone, most MS pt get better during pregnancy if they get worse after delivery use IVIG or put them back on inf they should not breast feed.
Apl ddx from ms in ms mri changes more corpus callusum involvement more periventricular more confluent lesion
in cadasil more temporal pole involvement
MS Masqurades
inf make vasculitis sarcoidosis devic psychosis worse
vasculitis more peripheral lesions
dissemination in time space no better explanation
left atrial myxoma instantenous symptom onset.
Red flag
normal mri
normal csf
no eye findings
no bladder symptom
Actual DDx
Leber optic neuropathy
100 conditions can mimic MS

MS Diagnosis CSF oligoclonal bands are seen in nearly all patients with subacute sclerosing panencephalitis and 83-94 percent of patients with definite multiple sclerosis. They are also seen in 25-50 percent of patients with neuroborreliosis, cryptococcal meningitis, Guillain-Barre syndrome, and other conditions. Many patients with neuromyelitis optica fail to have oligoclonal bands in CSF.
Numerous studies of the cognitive disturbance in multiple sclerosis demonstrate the absence of classic cortical (e.g., language, cognition, visuospatial, memory) impairments but clearly show a slowing of information processing.
Postinfectious disorders
- Brachial plexus neuritis
- Optic neuritis
- Post infectious Cerebellitis
Brachial plexus neuritis- Parsonage Turner synd, develops suddenly, may last for weeks, shoulder pain inc c shoulder arm movement but not c neck movement or Valsalva
In neuromyelitis optica, women are affected up to four times more often than men and the clinical course of the disease is frequently rapidly progressive. Devic disease is much more common in Asia, with up to 8% of multiple sclerosis cases in Japan being of the Devic type. Oligoclonal bands are absent from the CSF in most cases. The presence of necrosis in spinal cord virtually defines the entity.
Significant keys to pathogenesis in multiple sclerosis may be associated with the topographic features of demyelinative plaques. Older plaques tend to be sharply, not poorly, demarcated from surrounding brain. In two thirds of cases, spinal cord, cerebrum, and optic nerves are equally involved, with sparing of one or another of these regions in less than 15% of autopsied patients. Gray matter, including cerebral cortex, is not spared even though the largest or most grossly visible plaques are in deep white matter. Plaques extend along veins, not arteries, in finger-like projections called Dawson's fingers. Subpial plaques are classically wedge-shaped, with a broad base near CSF pathways.

MS Diagnosis INO or MLF Syndrome
MLF carries fibers from vestibular nuclei to CN III, IV, VI
synd c/o
- medial rectus paresis on attempted lateral gaze
- intact convergence diagnostically important
- mono ocular horizontal nystagmus in the abducting eye
Etio- MS, Stroke, other demyelinating lesions ADEM, tumors, infection
MS Treatment Complications tx
amantadine 100 mg bid
modafinil (helps concentration, energy, no withdrawal can take it whenever needed, Kick in in 1-2 hours),
Modafinil 100 or 200 mg tab
start at 50 mg qam increase by 50 mg qweek to max 600 mg/day
SEs sleep disturbances, HA, jitteriness
4 aminopyridinr acts on K channels prolong action potential also helps memory and heat tolerance
for weakness and fatiguibility may cause sz start 5 mg qd, increase by 5 mg qweek up to 10 mg tid SEs perioral numbness
acts centrally 3,4 aminopyridine acts peripherally good for LEMS
SSRI- prozac, lexapro
Dantrolene also act sarcoplasmic reticulum cause weakness
Diazepam drowsiness
Baclofen tid better because bid causes more drowsiness
increment qweek 10 mg
Zanaflex tizanidine tid better
increment 2 mg qw or even 2week
also helps bladder so you can try it before detrol-LA (causes constipation)
Botox for local spasticity
neurontin 600 mg tid
AEDs tegretol, trileptal, lamictal
DYSYNERGIA- flomax, cardura, massage over bladder, or small batery charged massager
while on INF no pregnancy (risk of misscariage)no Breast Feeding (INF secretion)
copaxone cautious to use
estriol natural immunosuppressive that is why baby not immunogenic
there is 25-30% increase risk of MS exacerbation postpartum
Can use CSs prophylactic for postpartum period until restart of INF
pulsetherapy one day Solumedrol 1000 mg IV q1-2 months per degree of severity
sometimes can use combination therapy pulse steroids + INF

MS Treatment Immunomodulatory best for MS
Solumedrol 1000 mg iv for 5 days or
1000 g iv 3 days then 60-50-40-30-20-10 mg taper
CSs shorten/or dec severity of attack not long term disability
significant relapse
- dec vision>20/60
- motor relapse
- cerebellar relapse
- gait relapses
MS present c
- optic neuritis
- spasticity/gait problem
- ataxia
- motor weakness
plasmapheresis for those that don't response to corticosteroids or DMD.
immunomodulatory reduce relapse 33% and secondary outcome dec of t2 mri lesions.
they have to be one drung long enough and committed.
if fail immunomodulatory
im plus azathioprin, mycophenolate, methotrexate, cytoxan
rescue therapy mitoxanthrone
clinically isolated synd.
if high T2 burden, gad enhancing, black hole
if patient fail change im to copaxone or vice versa
add DMAgent aza, myco, metho
or add mitoxanthrone
for secondary progressive methotroxate or cytoxan pulse therapy knly for <40 years.
Mitoxantrone 12 mg/m2 monthly x 3 then q3month for 8 dose
at least 1 year of immunomodulatory tx should be tried before adding DMDrugs
if mitoxantrone completed then add CSs and/or Imuran to INF

Rebif 33% Avonex37% reduction in disability, Betaseron 29% Copaxone 12%
Rebif vs Betaserone more effective less side effect
flu like symptoms more in first 8-12 week, can use NSAIDs or small dose prednisone 5-10 mg one dose at time of shot also
Can start Avonex 1/4 or 1/2 usual dose and increase by 1/4 dose
check CBC, CMP, LFTs,
TFTs , B12
Testosterone for decrease libido use cream or shot
IVIG used postpartum when can not tolerate pulse therapy
or they have major steroids side effects or they failed IV steroids or if pt have very high IgG index
INF failure
monthly solumedrol
use imuran cellcept
next use monthly cytoxan (in woman who does not want to become pregnant)
next use IVIG Plasmapheresis
mitoxantrone no use too cardiotoxic
MS Treatment Mito
MS Treatment MS Types
Primary progressive MS (tend to male, older, different MS)
Sec progressive MS
progressive relapsing MS
AAN Guideline on MS Tx
short term pulse benefit
no benefit of longterm tx
regular pulse tx may be useful
INF B- reduce attack rate by third also dec T2 MRI lesions as well as disability progression (most important)
dose-response relationship or more accurately frequencyof adm c response, NAb probably less c inf b a avonex c/t betaseron SQ may cause more NAb
Cyclophosphamide- possible benefit only in younger pt c progressive MS
Methotrexate- possible benefit in pt c progressiveMS
Azathioprine- reduce therelapse rate
Cladribine- reduce Gd enhancement but no change in attack rate or disease progression
Cyclosporine- not rec b/o nephrotoxicity
Mitoxantrone- reduce attack rate and disease progression, 5-12 mg/m2 usuall dose, q3months
check cardiac EF while on drug
IVIG- no benefit
PExchange no value in tx but may be useful in severe attack of demyelination
Sulfasalazine- no benefit
Betaserone esp. good forMS pt c spinal involvement
IV Steroids is must in optic neuritis as well as transverse myelitis or acute cerebellar ataxia, not very useful for sensory attacks, po steroid for optic neuritis worse than giving nothing and may be sued.
for spinal cord injury must give 1000 mg first hour and then 1000 mg over next 23 hours it is must will reduce ASIA class
demylination can happen with copper def. either cerebral demylination or like subacute combined degeneration in spinal cord Tx copper 2 mg po qd

MS Treatment MS
chlamydia or HLA DR2 may play role in pathogenesis
monosymptomatic disease then relapsing remitting then secondary progressive
MRI lesions >4 mm PV or juxtacortical
MS is demylinating but later on have axonal loss
Rebif 44 mcg Sc tiw c/t 30mcg Avonex im qweek had less relapse (18%)or MRI lesions
MS half common in aferican american
associated with hla dr2
b cell autoantibody esp against mog is importnt in addition to main t cell response.
PRISM4 Rebif 44 ug 3/week had less burden of disease or relapse c/t 22ug or placebo
Avonex dose comparison study no diff in 22 vs 66 but ug 22x3 qweek had better response less relapse so
frequency of admin more important than higher dose.
SE of inf- flu like give ibuprofen naprosyn, depression, impaired LFTs , dec WBC check lft and cbc q3months
NAb less in Avonex but not necessary do poorly but if they develop in high titer they may get worse. Then you can give drug
holiday or switch them to Copaxone
Women c MS we didn't see breast cancer
some issues in MS
Primary prophylaxis in high risk ind
when gets pregnant shold stop inf give Copaxone
DMAgents such as CS IV 5days q 4months,
Neuroprotection- c NGF or glioprotective agents or dec nitric oxide or glutamate damage to CNS
nitrous oxide used in dentists or NASCAR cars can block B12 and they develop subacute combined degeneration or sensory ataxia
Atrophy in brain volume is more correlated with MS disability c/t no.of MRI lesions.
What time do u measure Nab- when
they have 2-3 relapses or severe relapses
How to manage- give higher dose inf if they were on low dose, or switch to Copaxone
Rebif maybe better more natural molecule, less Nab c/t Betaseron, tiw c/t qod of Betaseron
Threshold for starting MS maybe >4
lesions in MRI or if they develop 2nd
MS Types
Primary progressive MS
Sec progressive MS
progressive relapsing MS
MS Treatment Tx initiation and f/u
- assess disease hx and baseline relapses
- rate of progression EDSS
- review tx option
- vit D 1200 u/day
- Ca
- pt make sure compliance c medications
- schedule visit q 3m first y then annually
- Get details of relapses affected part to have accurate est of disease progression
- f/u MRI annually to monitor disease progression or show the pt improvement. MRI doesn't correlate c disease activity.
new Gd, new T2 lesion, number of black holes T1 hypotense lesions, and brain atrophy will be seen in MRI.
if not sure about dx f/u MRI in 3 (MDonald)-6 (practice for insurance)months advisable
if MRI normal after a year less likely.
if patient relapse on INF first check NAb if neg relapse within 1 year reasonable or you can increase INF dose, but if titer high change to copaxone alone or copaxone c pulse tx q month.
If pt male or new lesion in spinal cord treat more aggresively. add DMD like
Imuran start 25-50 mg/day titer up to max hematological criteria MCV, Lymphoid ratio.
INF therapy practical points:
1- Dose escalation 25% first week, 50% 2nd, 75% of dose 3rd week then full dose
2- Inject early evening so person is sleeping when inf peaks in 8-10 hours
3- Use NSAIDs or Tylenol 1 hour or with injection or 10-20 mg prednisone weekly with Avonex
4- How to inject, Sites and Rotate sites
5- CBC c Diff, LFTs every 3 months in first year then twice a year.
6- Check TSH once a year

Drop mets
seeding through CSF can happen in
- medulloblastoma
- ependymoma
- anaplastic glioma
- germinoma
- chroid plexus tumors
Meningitis Carcinomatosis
HA treatment- Steroids and external beam radiation
Multiple cranial neuropathies

type I pathology neurofibroma
in spinal cord and nerves, plexiform neurofibroma in plxus esp. brachial also associated with optic glioma

type II path schwanoma
Pituitary tumors
mass effect (infarction)vs endocrine effect (mostly d/t PR, GH, ACTH, rest of them cause less endocrine effect)
- Brmocriptine 2.5-5 mg po tid
- Cabergoline 0.5-1 mg twice a week less nausea less hypotension
- mainly surgical tx
- Somatostatin or GH or dopamine agonists
for GH evaluation should measure somatomedian or IGF-1 the endproduct secreted from liver.
monitoring tumor response to somatostatin analoge check GH (less reliable), IGF-1, Tumor size in MRI
normalizing IGF-1 normalize lifeexpectancy of pts.
GH Agonist- Pegvisomant recently approved for acromegaly cross link GH receptors
Cushing's disease
the pt presented c hip fx
- 24 h urine for cortisol
- Poor suppressibility of ACTH Cortisol by Dexamethasone
- DHES level main adrenal androgen
- Petroseal venous sampling, more reliabe c CRH stimulation, co firm pituitary source of ACTH
- GAMMA KNIFE, PROTON beam, radiaion if surgery not possible
Pituitary destruction hormonal def.
most important abundant ACTH then TSH, then less important GH, PR, LH, FSH
causes- trauma, infarction, infiltrative disease, hypophysitis
preop evaluation-
cortisol am
Gonadal hormones, LH, FSH
CMP, urine SG for ADH def.
postoperatively you should check the same hormones after 2-3 weeks
Suspect hypothalamic disease when:
DI or inc prolactin but less than 200 ng/ml
postoperatively check again for visual field defect.
pitutary enlargement in MRI
check for deficiency if there is replace and watch them for a while, if they have excess more in favor of tumors but enlargement could happen c pregnancy, hypophysitis or infiltrative disease eg sarcoidosis.

Neoplasms Brain tumors - Intraventricular tumors
Chroid plexus papilloma
Colloid cyst
SEGA subepengiantcell astro
Neurocytoma central
-Corpus callosum lesions
Demylination MS Marchiafava Bignami
Butterfly lesions (GBM, Lymphoma, PML)
Common Sellar Masses
Pituitary adenoma apoplxy hemorrhage lymphocytic hypophsitis
Empty sella syndrome
Mets breast
Rathke's cyst
Optic glioma or hypothalamic glioma
MRI DDx of dural based mass meningioma and its mimics:
Solitary fibrous tumor
Rosai-Dorfmann disease
Granulocytr sarcoma (chloroma)
Solitary dural mets
DDx of a solitary mass in lumbar cistern: meningioma, schwanoma, paragaglioma of the filum, ependymoma myxopapillary
Common tumors that rarely mets to brain- prostate, cervix, sarcoma in general, scc of skin
Multiple Tumors in MRI-
Multifocal- GBM, Primary CNS Lymphoma
ddx c abcess, demyelination (open ring sign to cortex)
Genetic predisposition-Neurofibromatosis:neurofibroma,schwanoma,meningioma
Tuberous sclerosis: sega
Von Hippel-Lindau:hemaangioblastoma,
renal cell carcinoma multiple masses are not always neoplastic
Neoplasms Brain tumors Acoustic neuroma
exact name vestibular schwanoma
no sex or side bias, unilateral x in NF2 which is bilateral, common in 4-5th decade
S & S
gradual sensorineural hearing loss esp to high frequency, unilateral tinitus, disequilibrium
hypoesthesia of face d/t CN5 earliest dec corneal reflex
fascial palsy may occur esp in large tumors but more present as fascial twitching
CN 9-10-11 dysfx
long tract signs
cerebellar tonsil herniation
Rinne ac>bc Weber lat to normal size
Brainstem-evoked response audiometry
MRI c GAD can detect >1mm tumor
SAME, cholesteatoma, aneurysm, hemangioma, lipoma, arachnoid cyst, mets
observation- 6 or 12 months MRI f/u esp if no neurological deficit or compression on brainstem
RT for tumor >2-3 cm
Neoplasms Brain tumors Brain tumors
Medulloblastoma is especially prone to widespread leptomeningeal metastases. Occasionally, this can be seen with glioblastoma and ependymoma.
Hemorrhagic mets
lung ca small cell
renal cell ca
GBM may be but not multifocal nor discrete lesion has butterfly appearance
Schwannoma arise from vestibular nerve but vertigo seen only in 20% of pt. most common unilat progressive hearing loss. unilat tinnitus. ifadvanced compression of facial trigeminal paresis also seen.
Up to 50% of patients with dysplastic gangliocytoma of the cerebellum have the stigmata of Cowden syndrome (multiple hamartoma syndrome), which include oral mucosa fibromas, multiple trichilemmomas, hamartomatous colon polyps, thyroid neoplasms, and breast cancer. About 5% of patients with Gorlin syndrome (nevoid basal cell carcinoma syndrome) develop cerebellar medulloblastoma, particularly the desmoplastic subtype. Type 2 neurofibromatosis patients are prone to develop spinal cord ependymomas, whereas subependymal giant cell astrocytomas are characteristic of tuberous sclerosis.
Neoplasms Brain tumors Brain tumors:
- Mets
- Glial ast, oligo, ependymoma
- Neurons
- Menings and Chroid plexus
difference between chroid and epyn epy no basement membrane chroid plexus tumors have bm.
-Tumor of uncertain origin: gc, astroblastoma, chroid glioma of 3rd ventricle, cerebellar liponeurocytoma
Neuronal supportive cells-
mature-gn then gf
PNS TUMORS: schwanoma, neurofibroma, perineurocytoma
1- Astrocytoma:
pilo,pxa, dia, sega
pilocytic ast, pleomorphic xantho ast, desmoplastic ifantile ast, subependymal giant cell ast
2- Oligo: oligodenroglioma, anaplastic oligodenroglioma
3- Ependymoma: Ependymoma, Subependymoma, Ana Ependymoma, Ependymoblastoma
Dysplastic gangliocytoma of cerebellum Lhermitte-Duclos
Mixed glial and neuronal-
Ganglio glioma
Desmoplastic Ganglio glioma
Dysembryoplastic neuroepithelial tumor DNET
Common features: infant children, mostly benign, hamartomatous features, well demarcated, Sz
Markers for germ cell tumors
germinoma-placental alk phos PLAP
Yolk sac tumors AFP
Choriocarcinoma HCG
Neoplasms Brain tumors Post fossa tumors
in children:
1- cystic astrocytoma in cerebellar hemisphere appendicular ataxia
2- medulloblastoma in midline typically vermis causing truncal ataxia and obstructive hgdrocephalhs
3- ependymoma obs hcp
4- brain stem glioma cn dysfx
in adults also consider mets
Neoplasms Peripheral nerves Malignant peripheral nerve sheath tumors most commonly arise in a neurofibroma, often of the plexiform type. They may also arise de novo in a normal nerve. Malignant transformation of a schwannoma or ganglioneuroma is rare. It is extremely rare to find these malignant peripheral nerve sheath tumors involving or arising from cranial nerves or cranial nerve neurofibromas.
Neoplasms Spinal cord tumors Spinal cord masses:
Intramedullary- Myelopathy Astrocytoma, Ependymoma, Oligodendroglioma
Extramedullary(intradural)- Myelopathy,Radicular pain
Schwanoma, Neurofibroma, Meningioma
Epidural(extradural)- Myelopathy,Radicular pain, Localized pain
Meta, Myeloma/Lymphoma, Lipoma Abscess, Herniated disk
50-60% mets(prostate,lung,breast, kidney)
10-20% myeloma/lymphoma
lipoma or lipomatosis complicating endogenous or iatrogenic CS excess
prostate mets to vertebral body.
or pedicle, pseudonormalization pattern.
8th nerve
cochlear nuclei- sup olivary nucleus-lat lemniscus- inf colliculi-med geniculatr-sup. transverse gyrus of temporal lobe
Based on the history obtained and the deficits found on examination, develop a differential diagnosis employing the "VITAMIN DEC" mnemonic:
1. Vascular
2. Infection
3. Trauma
4. Autoimmune/Inflammatory
5. Metabolic/Toxic
6. Iatrogenic
7. Neoplastic
8. Degenerative
9. Electrical
10. Congenital/Familial
Brain hemispheres
Taste sensibility is represented in the parietal operculum (area 43) and adjacent parainsular cortex.
The insular cortex receives visceral nociceptive input via the ventromedial posterior (VMPO) thalamic nucleus.
Circumventricular organs
periventricular areas s BBB that sample blood or monitor CSF and modulated by seretonin from dorsal raphe nuclei
6 center around 3rd vent & diancephalon
1- Pineal gland
2- Median eminence, infundibulum and neurohypophysis
3- Subfornical organ
4- Organum vasculosum of lamina terminalis
5- Subcommisural organ (vestigial remnant in human, x b/o has BBB)
6- Area of postrema (x b/o is paired, reason why L dopa cause NV, dopamin can not pass BBB and through here it affects CTZone)
Neural crest derivatives
- sympathetic chain need NGF
- dorsal ganglia(capsule cell)need NGF
- chromaffin cells
- schwan cell
- melanocyte
axoplasmic flow bidirectional, retrograde displayed by ...., colchicine inhibit it.
Microglia from mesoderm
Glia Oligo Schwann Ependymal Tanycytes and neurons from ectoderm
- subfalcine paraparesis babinski
- uncal pca hemiparesis
- tonsilar res depression
- central everything drops in midline
- upward cerebellar herniation
pontine sign
Papez circuit
plars a critical role in the transfer of information from short term memory to long term memory and its emotional component.
ento rhinal cortex- dentate gyrus- CA3-CA1- Subiculum-fornix-mamillar body- ant. thalamus-cingular gyrus- hippocampus
damage to
- basal forebrain (septum, nucleus basalis, orbitofrontal gyrus) cause Alz
- dorsomedial thalamus Korsakoff
- bil limbic Herpes, hypoxic encephalopathy, vascular lesion
- bil amygdal Kluver-Bucy
sympthic origin fromparaventricular nucleus of hypothalamus.
most vulnerable part ofspinal cord to ischemia is T4-T6
The anterior choroidal artery arises from the internal carotid artery distal to the origin of the posterior communicating artery. It has a long subarachnoid course, enters the inferior horn of the lateral ventricle through the choroidal fissure, and supplies the amygdaloid complex, hippocampal formation, globus pallidus, and the ventrolateral portion of the posterior limb and the entire retrolenticular portion of the internal capsule.
The inferior cerebellar peduncle connects the medulla to the cerebellum and contains the dorsal spinocerebellar tract, cuneocerebellar tract, olivocerebellar tract, and the vestibulocerebellar tract. The trigeminocerebellar tract lies within the superior cerebellar peduncle and would be spared in a lesion confined to the inferior cerebellar peduncle.
Unlike the relay and association nuclei of the thalamus (dorsal thalamus), the reticular nucleus (ventral thalamus) does not project to the cerebral cortex. It receives inputs from the cortex and projects to the other thalamic nuclei, and is critical for thalamocortical synchronization, particularly generation of sleep spindles.
The anterior choroidal artery supplies the lateral part of the medial segment of the globus pallidus, the target of pallidotomy in patients with Parkinson's disease. The posterior communicating artery supplies the medial part of the medial segment.
The chemoreceptor trigger zone is located in the area postrema. ,
Alexia without agraphia follows combined damage to the dominant medial occipital region and the inferior fibers of the splenium of the corpus callosum. This is in the distribution of the posterior cerebral artery.
post choroid a. arises from PCA supply pineal gland, tectum, chroid plexus of third and lat ventricles. ant. choroid artery arise from MCA supply hippocampus, amygdale.
recurrent artery of Hubner from ACA.
Neuroanatomy Cranial nerves All fascial muscles supplied by 7, x master, temporalis, med lat pterygoid, tensor veli palati, tensor tympani, ant belly of the digasteric, myelohyoid
Neuroanatomy Cranial nerves Facial nerve palsy
- upper stroke
- in Pons Millard Gubler, Foville, Brissaud
- in subarachnoid or in internal auditory meatus with CN 8 palsy
- before geniculate ganglion ear canal pain, dec lacrimation
- before stapedius hyperacusis
- before chorda tympani f weakness,loss of taste, dec salivation
- in fascial canal or ouside stylomastoid only fascial weakness
branch to occipitofrontalis causes weakness in raising eyebrow
- Bell(if complete Prednisone 1mg/kg/day for 10 days then tapered over 5 days, if incomplete Prednisone 1mg/kg/day for 5 days then tapered over 5 days, can combine Acyclovir 800 mg po five times a day if suspect Herpes),
- Belpharospasm(Meige if loer face involved, Tx Botox),
- Hemifascial spasm(exacerbated by alkalosis, ddx c focal sz, etio aberrant vascular loop in subarachnoid, Tx decompression, CBZ, Botox),
- Fascial myokyma (benign or in MS, , Brain stem glioma,Stroke)
Neuroanatomy Cranial nerves The foramen ovale transmits the mandibular division of the trigeminal (V) nerve. The foramen rotundum transmits the maxillary division of the trigeminal (V) nerve.
The nucleus of the tractus solitarius (NTS) contains the first central neuron for the baroreceptor afferents. Lesions involving the NTS produce fluctuating hypertension mimicking a pheochromocytoma.
The following structures travel through the various foramina: foramen rotundum -maxillary nerve; foramen ovale -mandibular nerve; foramen spinosum -middle meningeal artery; foramen lacerum -internal carotid artery; jugular foramen -glossopharyngeal nerve, vagal nerve, spinal accessory nerve. The internal carotid artery would be affected by a fracture through the foramen lacerum.
Derivatives of the alar plate include the cerebellum, inferior olivary complex, quadrigeminal plate and
the red nucleus. Derivatives of the basal plate include motor nuclei of cranial nerves in the nucleus ambiguus that provides motor neurons to the striated muscles of the larynx and pharynx via the vagal, glosspharyngeal and accessory nerves.
The rubrospinal tract is concerned with control of tone in flexor muscles. This tract arises from the red nucleus, crosses in the ventral tegmental decussation, and lies anterior to the corticospinal tract in the lateral funiculus.
Nucleus Solitarious is the neuron for baroreceptors. lesion can cause fluctuating BP like pheochromocytoma
DDx in neurology
Jandressic maneuver
increase GABA efferent discharge to muscle spindle. to enhance reflex
defined by direction of fast component horizontal, vertical, rotational, diagonal
2 type jerk vs pendular (oscilliations of equal velocity)
localization- vestibular system including end organs and vestibular nerve, brainstem, cerebellum flocculus (peripheral causes can be suppressed by fixation )
drugs eg AEDs, barbiturates, tranquilizers, etoh, phenotiazines, Li or OP toxicity
vascular, neoplastic and demyelinating lesion of brainstem
floccunodular lesion of cerebellum
congenital nys
gaze evoked nys usually drugs,
upbeat nys usually pontine lesions
downbeat nys when look down and lat usually in cervicomedullar junction lesion eg Arnold Chiari, basilar invagination, paget, foramen magnum meningioma
see-saw nys one eye rising one eye falling parasellar mass esp interstitial nucleus of cajal
convergence-retraction nys midbrain post commisure eg pineal tumors, parinaud's synd
congenital- prism, surgery, contact lens
Baclofen for periodic alternating nystagmus (90 sec one direction 90 sec another direction, in cervicomedullary junction, brainstem, cerebellum)
trihexyphenidyl for MS pendular nys
gabapentin for MS pendular nys
Botulinum toxin A
Ocular oscillation
differ from nys because no distinct slow or fast component. subtypes
ocular bobbing downward jerks
ocular dipping
ping pong oscillations
oculopalatal myoclonus
flurries of REM ocular flutter(purely horizontal) vs opsuclonus (multidirectional)
sup oblique myokyma
spasm nutans
papapa/bababa tatata/lalala kakaka/gagaga respectively show lip(p) tongue(t) palate(gag) weakness
Encephalopathy definition- 3 of these
change in LOC
change in cognition or personality
bil hemisphere or anywhere down decending pathways to upper pons
cause Cheyne-Stokes (it can also produced by any encephalopathic states as well as severe CHF)
ventral to aqueduct or 4th ventricle cause central neurogenic hyperventilation (it may be associated with neurogenic pulmonary edema and often resolves with correction of metabolic abnormalities)
respiratory centers in pons medulla cause either of these apneustic (pontine level)/ataxic(medulla level )/ Ondine's curse (failure of automatic respiration during sleep)
pupillary light reflex preserved in met (x mydriatic in one eye or breathing tx)abn in structural lesion hypothalmus horner
midbrain midposition fixed pupills
pons pinpoint
medulla horner
Lhermitte sign
MS, B12 def, radiation mgelopathy
seen in demyelination of post column
Amaurosis fugax in diseases of ICA not MCA

Acute autonomic neuropathy
small fiber
sympathic or parasympathic insufficiency, relative sparing of somatic nerves so less paresthesia
problem c OH, NVD, Constipation, urinary retention, impotence, pupillay dilation, dry eye or mouth
Etio- autoimmune (preceding viral infection, inc CSF Pr), paraneoplastic LEMS (dry eye, mouth, proximal weakness), DM, Entric neuropathy (acute abdomen, watery diarrhea), Botulism (pickle, honey, acute cholinergic neuropathy, diplopia, blurred vision, diarrhea/constipation), Porphyria (abdominal pain, diarrhea), Antineoplastic vincristin, taxol, cisplastin, amiodarone, heavy metal, organic solvents (hexane),
Dx- Supine/Standing noreepinephrine, sweat test (absence of sweating with alizarin), QSART quantitative sudanomotor axon reflex test (identify posganglionic sympathtic neuropathy)
-Prednisone 50 mg qd for 2 weeks then taper
-IVIG 2 gram/kg over 5 days
- Plasma exchanfe

Acute weakness
Myasthenia gravis; Myoglobinuria
Myosin loss myopathy; Carnitine dec
Periodic paralysis: X-Episodic Xp22
Hyper K+: SCN4A; KCNE3
Andersen: KCNJ2
Electrolyte disorders: K+ é inc or ê dec;
Mg é; PO4 ê; Barium
Rule out: Neuropathy; Spinal cord
- 2-5% untreated SLE
- 10-15% Systemic Sclerosis
- Common in Sjogren, PM, Sleroderma
- in 75% of elderly
- in 20% pt c rheumatic disease
- in 2% of normal nonelderly
titer >= 1/160 significant
- homogenous SLE RA
- speckled SLE Scleroderma Sjogren MCTD
- peripheral SLE
- nucleolar Sleroderma
Anti ds DNA or Anti sm ab are specific for active SLE and lupus nephritis
Antibodies + Myopathy
MG: Anti-AChR
Binding & Modulating
MG + Thymoma: Anti-striational
vs. Titin; Actinin; Ryanodine R
LEMS: P-type Ca++ channel
t-RNA synthetase (Jo-1):
Lung; Raynaud's; Arthritis
Signal recognition Particle: Acute
Mi-2: Dermatomyositis; Nail D
PM-Scl: PM + Scleroderma
Decorin: M-protein; Myopathy
Bariatric surgery, Neurologic complications of
nutritinal def.
- mineral iron, ca, mg, po4, copper
- vitami def. B1 B2 B6 B12 D E, Niacin
- Lactic acidosis
- Rapid fat metabolim or loss of carnitine
Encephalopathy B1
B6 def induced Sz
Myelopathy B12, copper
Ataxia vit E
Vitamin B1-
Brachial plexupathy
Formed by ant rami of C5 T1
Etio- most common injury(hematoma or in coagulation abn),then tumor infiltration (Pan coast), radiation(5 months after, incontrast to tumor infiltration upper or entire plexus affected, pain is less common, lymphedema is frequent), infection
Upper trunk C5C6- ErbDuchenne lat aspect of arm forearm numbness proximal weakness
Lower trunk- Klumpke C8T1-medial aspect of arm forearm, hand weakness intrinsic, finger flexor extensors, maybe d/t Pancoast tumor
Postinfectious disorders
- Brachial plexus neuritis
- Optic neuritis
- Post infectious Cerebellitis
Brachial plexus neuritis- Parsonage Turner synd, develops suddenly, may last for weeks, shoulder pain inc c shoulder arm movement but not c neck movement or Valsalva, 1/3 bilat following inf or vac, Px good but need PT/OT ROM Exerciss to prevent weakness atrophy
dx c NCS/EMG, Steroids or IVIG may help
radiation cause more upper plexopathy because less surronding tissue
radiation vs neoplastic infiltration-
radiation more upper plexus
radiation NCS no change
radiation EMG myokyma

Bulbar dysfunction
MG; Thyroid; Cranial nerve D
Oculopharyngeal MD
Distal myopathy (MPD2)
Polymyositis: IBM; Scleroderma
Motor neuron D: ALS
Pseudobulbar palsy; Fazio-Londe
Brown-Vialetto-van Laere; BSMA
Bent spine syndrome
abnormal posture of the trunk thoracolumbar spine which increase during walking and abates with recumbent positions.
-NMD eg ALS, IBM, Nemaline myopathy, focal paravertebral myopathy, MG
PD, MSA, Postencephalitic parkinsonism
primary dystonia or secondary dystonia due to PD or structural lesion of brain or spinal cord
- Stroke
- Spine deformity
- Idiopathic or psychogenic
- Misc drug, graves, paraneoplastic, Tourette
Some patients respond to Botox injection into rectus abdominis muscles if clinical evidence of contraction of the muscle like 300-600 u for both side.
Cardiac disorders
Dystrophy: DMD/Becker;
Myotonic; McLeod;
Emery-Dreifuss; Barth;
Scapuloperoneal; Desmin
Polymyositis; Nemaline rod
Acid Maltase; Debrancher
Carnitine ê; Desmin é
Mitochondrial; Amyloid
Drugs: Metronidazole;
Emetine; Chloroquine;
Clofibrate; Colchicine
Cardiomyopathy + cores
Periodic paralyses
CNS + Myopathy
Congenital MD: Santavuori (POMGnT1; 1p32);
Merosin (6q22); Fukuyama (Fukutin; 9q31)
Integrin-a7 (12q13)
Dystrophy: DMD; McLeod
Myotonic; PROMM; HIBM (9p13)
Metabolic: Thyroid; Mitochondrial
Acid Maltase: Aneurysms
Phosphoglycerate Kinase
Encephalopathy; Pipestem capillaries
Hearing loss: FSH; Scapuloperoneal
Complex regional pain syndrome
type I= RSD
type II =Causalgia demonstrable peripheral nerve injury
progressive neurovascular pain characterized by
-pain, burning hyperesthetic pain
-vasomotor instability color temp of skin (hyperhydrosis,hypertrichosis)
-trophic changes dystrophic skin nail
happen after traumatic or nontraumaticdamage to soft tissues or bone evev after MI
Immersion test-
immerse exteremity in warm water
absence of wrinkling in fingers toes is suggestive of a lesion in the central or the peripheral sympathetic pathway also seen in DM neuropathy
xray may show soft tissue swelling or patchy osteopenia
bone scan inc activity around joints
sweat test

ddx ms, neurologic or vascular problems, neoplasia eg bone should not be missed
NSAIDs such as ibuprofen
acetaminophen with codeine or with oxycodone
Vioxx in adults
ketorolac iv or im
AEDs tegretol, neurontin, dilantin
lidocaine patch or ELMA cream
steroids medrol dosepack or iv solumedrol
antispasmodic baclofen Zanaflex
vitamin c after fx
bisphosphonates osteoclast inhibition
Extremity elevation
distal to proximal massage
Local heat or cold compress
Sympathetic nerve block
Spinal cord stimulation
Bethlem Myopathy
Congenital MD
IM drug injections
Rigid spine syndrome
SMA: 5q; X-linked
Tel Hashomer
- Increased
rhabdomyolysis, hyperthermia, myoglobinemia, etoh, hypothyroidism, idiopathic essential, myopathy/myositis, mitochondrial disorders, Glycogen storage disease, McArdle, muscular dystrophy, mild dystrophies, cramp myalgia syndrome, last third trimester of pregnancy, substance abuse, snake bite,
check CPK, Aldolase, LA, Pyruvate, Anti GAD for stiffman synd, EMG, Muscle bx

CK: High > 1,000
X-linked: DMD/Becker
Recessive: 2A-2I
Dominant: 1C; Ankle contractures
Distal myopathy: Miyoshi
Acid maltase
Acute damage: Injection
Rhabdomyolysis; Trauma
Thyroid: Hypo-

- Decreased
hyperthyroidism, hereditary spherocytosis, CVD, malnutrition, lab error, 8-20 weeks pregnancy

Cramp, stiffness, exercise intolerance
*d/t abn muscle activity
- Neuromyotonia(Issac synd,ab to K channel, myokyma, multiplets discharge on spontaneous EMG), - Schwartz-Jampel synd(short stature, bony deformity),
- Stiff person synd(truncal spasm hyperlordosis, triggered by startle or emotional upset, ab against glutamic acid decarboxylase, pancreatic islet cell, DM, tx diazepa, baclofen),
- Myotonia congenita or fluctuans,
- Systemic eg dec T4, dec cortisol, uremia, dec Ca (hyperparathyroidism), Mg, Strechnine poisoning (rat poison oderless, glycine antagonist)
- Cramp myalgia syndome
- MMN c CB
- Cervical or Lumbar spondylosis
- Metabolic myopathies, McArdle, CPT def.
Tx- Ultram, Baclofen, Ca 1500 mg/day, Mirapex 0.25 mg qhs-bid, if fails above may purse muscle bx to look for metabolic myopathies or mitochondrial disorders esp if CPK is high.
* Dec muscle energy carb(myophosphorylase McArdle), LCFA or VLCFA (carnitine palmitoyl transferase 2 def, VLC Acyl Co A dehydrogenase def.), Mitochondrial myopathies
* Myopathies eg Cramp/Tubular aggregates, Familial X linked Myalgia/Cramp, Malignant hyperthermia, NMS, Rigid Spine Synd, Rippling Muscle disease

Normal: Single Muscles
Post-contraction; Sleep
Electrolyte: Dehydration
Na, Mg, Ca, Glucose
Thyroid; Adrenal
Drugs; Pregnancy; Spinal stenosis
Cramp-fasciculation; Familial
Myopathy: Becker
Motor neuron: ALS
Electrically silent: phosphorylase
Rippling muscle; Brody's
Cramp treatment
avoid dehyration
check thyroid adrenal low sodium
check diet pills stimulant
myopathic drugs
quinine 200 qd or bid or tonic water
ca 500-1000 mg/day
mg gluconate 500 mg a day
vit E
riboflavin 200 qd or bid
Ginko biloba
Japanese quince
Critical care neurology electrodx
undx nm disorder
spinal cord damage
critical illness polyneuropathy
loss of muscle mass
electtolyte disorders
systemic illness SIRS or SEPSIS
diff weaning off the respirator
premorbid disease sirs
neuromuscular agents and steroids can impair muscle nerve microcirculation
Critical illness polyneuropathy usually after sirs and septic encephalopathy polyneropathy dec ref abs babinski red in cmap with minor changes in latency dec snap amp fibril and sharp waves may not
appear til 3 weeks
can happen after burn and organ transplantation
acute motor neuropathy after curar agents used
other possibles gbs oraxonal gbs or cidp, vasculitis, drugs metronidazole, nitrofurantoin, amiodarone, antineoplastic, antiretroviral, cmv, dm, heavy metal, hepatic failure neuropathy
thick filament myopathy dt steroids and nm blocking agents
cachectic myopathy type ii atrophy
acute necrotizing myopathy dt infection or chemicals
either of feeling of exhaustion after
Critical illness neuropathy
skeletal-muscle wasting
RFs- sepsis, meds eg neuromuscular blocking agents, corticosteroids and aminoglycosides
Tx- intensive insulin therapy with drip to keep glu between 80 to 110 (130) dec mortality from 8% to 4.6%, dec polyneuropathy by 44%, infections by 46%, ARF by 41%, transfusion need by 50%, less prolonged mechanical ventilation
NEJM 345;19:1359-1365 Nov 2001
wrist,2&3 flexion and thenar n are spared since these nerves branch befor carpal tunnel
tinel phalen flick (shaking of hands to relieve paresthesia)
prolonged distal latency
- Wrist splint
- Medrol dosepack
- local steroid injection
25 gauge needle to inject 1 ml of 1 percent lidocaine just to ulnar side of the palmaris longus tendon, proximal to wrist crease. Aim needle at 30 degree angle. if no paresthesia on injection of a small amonut of lidocaine, the rest of lidocaine injected followed by depot CS.
Limit injection to 3 in a year.
Complications- tendon rupture, nerve irritation.
Surgery- when pt has s & s suggestive of axonal loss- constant numbness, symptoms more than one year, loss of sensibility, thenar atrophy
CVD, Autoimmune disorders
SLE-sz (in 30-54%),sensory neuropathy, sychiatric symptoms, stroke in 15% of pt mainly d/t coagulopathy, cardiac valve abn rather than CNS vasculitis.
BECHET- aseptic meningitis 10-50% or dural thrombosis
SJOGREN- dorsal ganglionopathy less motor
RA- no direct involvement but indirectly through cervical spine abn myelopathy
Dermatomyositis PM

- prox muscle weakness esp shoulder abd, hip flex causing difficulty climbing stairs, combing hairs, rising from chair.
- inc cpk, aldolase, ab myosin specific ab anti jo1
- emg low amp polyphasia, spont fibrilliations
- muscle bx in DM IC deposition perifasicular inflammation vs PM Tcell attack directly on muscle fibers
- in case of DM heliotrope rash and over finger knuckles
if adult do paraneoplastic w/u inc
CT of chest/abd/pelvis
CA 125
Transvaginal US
Diabetic Amyotrophy
DM lumbosacral plexopathy d/t inflammatory vasculitis of LS plexus
- asymmetric onset
- pain in proximal thigh
- affecting femoral, obturator, sciatica peroneal in order
- weight loss 10-40 pound
- minimal back pain or mri changes
- more common in elderly in noninsulin dependent DM
- may be associated with foot drop
or co existing distal symmetrical polyneuropathy
- pathophysiology like parsonage turner is axonal loss
- r/o paraneoplastic causes CT of chest abdomen pelvis with attention to plexus,
- LP to rule out carcinomatose meningitis cytology
- routine PN w/u including SPEP, IFE
- Lyme screen
- MRI of L spine or LS plexus
Lyrica 100 mg tid
Narcotics fentanyl oxycontin
IVIG 0.4 g/kg in 5 days measure Ig A before
ASA or Plavix
60% recovery in 1-2 year

DM thoracoabdominal neuropathy
ddx lyme, shingles, sle, autoimmune
Distal & Proximal weakness
Dystrophy: Myotonic; FSH
Myopathy: Congenital; Distal
Glygogenoses: Debrancher
Phosphorylase b kinase
Neuropathy + Myopathy: Paraneoplastic;
Sarcoid; Mitochondria; HIV;
Drugs (Amiodarone; Doxorubicin
Colchicine; Chloroquine)
DM Neuropathy
- axonal pp temp
- demyelinating pos vib
- autonomic erection con/dia dysrrhythmia OHypotension
- amyotrophic
- diabetic CIDP
they can have AIDP on top of these
Tx- plasmapheresis, or IVIG
after plasmapheresis, check c Peter Dyck's neurologic disability scale (NDS) should be dec after plasmapheresis.
neurologic causes
- PD
- Stroke, bulbar palsy
- MG
- Myopathy
- MS
causing more high dysphagia as cricopharyngeal spasm.
Mechanical, tumor, scleroderma, achalasia, reflux stricture
Focal hand atrophy
(Split hand phenomenon, Focal amyotrophy)
atrophy of hypothenar or thenar
1- ALS
2- MMN c CB
3- Neurogenic thorasic outlet syndrome, cervical rib
4- DADS neuropathy, distal acquired symetrical demyelinating polyneuropathy
5- Multilevel cervical myelopathy
6- Nerve root injury C7-T1
7- Hirayama disease Ant myelopathy due to slack dural canal in spinal canal and pressure from dural canal on vascular supply of ant horn cell or epidural venus congestion, usually asymetric hand atrophy dx confirmed by flexion MRI look for post dural enhancement and mass effect or phase-contrast MRA for epidural venus congestion.
8- SMA autosomal dominant distal spinal muscular atrophy, mild disease, lower limb predominance involvement
9- SCA 3, spinocerebellar ataxia type 3 Machado-Joseph disease, late onset 40-60 yo, purtogeause descend, slow progression, cerebellar ataxia, cramp, fasiculation, muscle atrophy, AD, CAG repeat
10- JMA juvenile spina muscular atrophy, focal amyotrophy, stabilization of disease, atrophy of C7-T1 innervated muscles, intrinsic motor neuron disease or results from mechanical distortion of C spine d/t neck flexion during growth
- cord compression b/b i can happen in 15% of GBS
- transverse myelitis
- botulism, tick paralysis, widow spider, lyme, campylobacter
- heavy metal, lead, mercury, arsenic, thalium
- porphyria esp if axonal feature on EMG
- HIV, Rabies, CMV, , EBV, Polio
- Paraneoplastic eg Lymphoma
botulism and polio don't have sensory deficits
GBS Forms
AIDP, AMSAN(worse px), AMAN
MF, Acute sensory Ataxia, Brachial form
clinical monitoring
FVC <1.5 stepdown ICU (risk of infection, ARDS, iatrogenic)
FVC<1 intubation
intubation when VC <15ml/kg
extubation when VC >25 ml/kg
Choice of Tx
AMAN or AMSAN can happen after C. jujeni (Ag mimickery with GM1, check anti-GM1) or H. Flu (Check anti-GM1); CMV infection (check anti-GM2); Mycoplasma infection (Check anti GalC ab)
- Inc DL, Late response > 130% ULN
- Dec CV < 75% LLN
- Asymmetry, CB >50% drop in CMAP amp, TD >15% inc in CMAP duration
(ddx for aquired vs hereditary demyelinating polyneuropathy)
- first abn inc F response b/o prox demyelination at root level (check in 2 or more nerves)
- sural sparing b/o its thick myelin sheet make it more resistant to inflam changes (compare sural with 2 abnormal UE SNAPs median,ulnar and radial)
- EMG demyelinating pattern no denervation, normal MUAP morphology, reduced recruitment in weak muscles
- best predictor for prognosis, dital CMAP (0-20% LLN in 3-5 weeks)
1- SNAP in median,ulnar, radial and sural for sural sparing pattern
2- Absent or prolonged F wave (and or absent H reflex?) in relatively normal distal CMAP of tibial and median or more nerve
3- CB, TD,focal slowing in 2 motor nerves
4- Repeat study in 3-5 weeks if distal CMAP is less than 20% of LLN bad prognosis
1 or 2 suggestive
1 and 2 highly suggestive
2 and 3 definite
Hereditary Myopathy Syndromes 1
Dystrophies: Limb-Girdle & Other
Dominant: 1A (Myotilin; 5q31); 1B (Lamin A/C; 1q11);
1C (Caveolin-3; 3p25); 1D (7q); FSH (Deletion; 4q35);
Cytoplasmic (2q24; 2q21); Emery-Dreifuss (Lamin A/C);
Myotonic (DMPK CTG rpt; 19q13); Spheroid body;
Bethlem (COL6A; 21q22 & 2q37); PROMM (ZNF9; 3q21)
IBM3 (Myosin HC2; 17p13); MD + Cardiac (6q23);
Oculopharyngeal (PABP2 GCG rpt; 14q11)
Desmin (2q35); aB-crystallin (11q22); Paget (9p13)
Diaphyseal (TGFB1; 19q13) dysplasia
Epiphyseal (COL9A3; 20q13) dysplasia
Recessive: Sarcoglycans- 2C (g; 13q12); 2D (a; 17q21);
2E (b; 4q12); 2F (d; 5q33);
2A: (Calpain-3; 15q15); 2B (Dysferlin; 2p12);
2G (Telethonin; 17q11); 2H (TRIM32; 9q31);
2I (FKRP; 19q13); 2J (Titin; 2q31); 4; Caveolin-3;
CMD: Nl CNS (FKRP; 19q13); Rigid spine (SEPN1; 1p35)
Respiratory failure (1q42); Ullrich (COL6A2; 21q22)
X-linked: Barth (Tafazzin; Xp28); Autophagy (Xq28);
Emery-Dreifuss (Emerin; Xq28); McLeod (XK; Xp21)
Becker & Duchenne (Dystrophin; Xq21);
Danon (LAMP-2; Xq24); Scapuloperoneal
Hereditary Myopathy Syndromes 2
Distal Myopathies
Welander (2p13): Late onset; Hands & Ant. Legs
Finnish & Markesbery (Titin; 2q31): Late onset; Ant Tib
Gowers-Laing (MPD1)(14q11): Early adult; Ant leg
Dystrophy + rimmed vacuoles (19p13)
IBM1: Quad weakness
IBM +: Paget's (9p13); Respiratory failure (6q27)
Vocal cord & Pharyngeal (MPD2) (5q31)
Myofibrillar myopathy: Desmin; aB-crystallin; Other
Nonaka & IBM2 (GME; 9p12): Quad sparing
Miyoshi & LGMD 2B (Dysferlin; 2p12-14)
Early adult; Posterior leg
LGMD 2G (Telethonin; 17q11): Teens; Ant leg & Prox
Hereditary Myopathy Syndromes 3
Other myopathies
Barnes; Congenital; Lipid; Glycogen;
Familial MG; Tubular Aggregates
Inflammatory myopathies
Antibodies: Decorin; SRP; Mi-2;
t-RNA synthetase (Jo-1 75%)
Mi-2 Ab; Adult vs Child
Microvasculopathies: DM; SRP
Granulomatous ± Sarcoid
Idiopathic myositis: Poly-; Focal
Inclusion body (IBM); Infectious
Mitochondrial D in muscle
Systemic disease: Drugs;
Collagen vascular; GVHD;
Malignancy; Toxic
Hereditary: IBM; FSH
Issac synrome
- continous or intermittent muscle twitching
- cramp, myotonia, myokymia
- increased sweating
- slowed movement
- age 15 60 max around 40
- severe cases bulbar symptoms
- autoimmune disorder d/t ab against voltage gated k chnnels on peripheral nerves
- exposure to toxins gold mercury
- tumors lymphoma, thymoma, lung cancer
- genetic
- Ab against VG K channel
- Ab against ganglionic nicotine AChR
- dph or cbz
- immunosuppression meds
- quinine,
- ginko biloba
Neuromuscular hyperexcitability syndromes
- Issac syndrome or neuromyotonia
- cramp myalgia synd
- rippling muscle syndrome
(wave of muscle cramp for 5 sec, myoedema by percussion, toe walking, muscle hypertrophy, muscle activity electrically silent, tx bnzd)
- focal neuromuscular hyperexcitability
6 approved label indications
primary immunodeficiency, B cell CLL, ped HIV, BMTransplant, Kawasaki synd., Acute ITP
IVIG in neurology
MS (for 5 days and then 0.4 g/kg every month), LEMS, Stiff person syndrome if fails other tx
also maybe good for infilterity, pamphigus

in pt with DM good prehydration and do it very slowly.
Large muscles
Overusage: Myotonia; Exercise
Neural Overactivity
Partial denervation
Endocrine: ê Thyroid; Acromegaly
Dystrophy: DMD; LGMD; Lipo
Infections: Cysticercosis;
Trichinosis; Schistosomiasis
Drugs: b2 adrenergic; Androgen
Storage: Glycogen; Amyloid
Fat; Gangliosides
Short stature: Schwartz-Jampel; Myhre
Livedo reticularis
- RA, SLE, APL Syndrome
- DM/PM, occult malignancy
- Hepatitis C, PAN
- Beurger's disease
- Amantadine, meds
- Cholestrol emboli
- Benign idiopathic, they have problem for the life
Lumbar plexupathy
Motor Neuron disease Tx
- Riluzole (Rilutek) 50 mg po q12h
(check for neutropenia, hepatotoxicity while on Rilutek)
reduce neuroexcitotoxicity by diminishing glutamate release, increase few months
to life expectency prognosis 5-10 years
side effects may include NV Dizziness weight loss and inc LFTs
Cox2 inhibitors neuroprotection Celebrex 100 mg po bid or Vioxx 12.5-25-50 mg po qd or Baxtera qd or bid
Coenzyme Q 10 mg po bid
Minocycline 100 qd or bid (watch for photosensitivity)
Antioxident vitamins A, C
Vitamin E 400 u po qd
MV or B12
Possible neurontin topiramate creatine brain derived neurotrophic factor, glial derived neurotrophic factor
for general discomfort can use NSAIDs Advil 800 mg po tid Naprosyn 500 mg po bid
less gastric effect
or Tramadol Ultram 25-50 mg po q6-8h
for spasticity, stifffness and abnormal movements
Baclofen (Lioresal)
Tizanidine (Zanaflex) 2-4 mg po q6h-q12h
Tx of psychiatric problems symptoms
Depression Zoloft 25 or 50 or100 mg qhs Effexor
PT/OT for stretching for contracture foot drop splints, Finger extension splints
Discuss limits of care with patient
Pt should have advance directive or living will for DNR or DNI orders
Hospice care: may need respiratory support tracheostomy intubation or PEG tube for nutriotion and dysphagia
Motor Neuron disease
Cervical meyelopathy
(Monomelic amyotrophy, Hirayama disease= segmental spinal muscular atrophy secondary to slack dural canal that cause vascular compromise to ant horn cell causing AHC ischemia, usually assymetric confirm with flexion MRI of C spine, may call it ant myelopathy)
Multifocal motor neuropathy with conduction block
Motor neuropathy with paraproteinemia or cancer
Motor predominant peripheral neuropathy
Primary lateral sclerosis (upper motor neuron disease)
Postpolio syndrome (asymetric weakness + areflexia+neutrophills in CSF and involvement of spine ant horn cell and brain stem motor neuron)
Postinfectious echo coxsaki HTLV-1 and HTLV-2
Hereditary spinal muscular atrophy
Lead or Aresenic exposure
Guam dementia
Motor system atrophy=Joseph Machedo disease

MRI of C spine with gad
CT of chest fo CA esp small cell lung ca
5-10% of ALS paraneoplastic like LEMS check serum or CSF Anti-Hu
24h urine for heavy metal
Serum Pr Electrophoresis (SPEP), ImmunoFixation Electrophoresis (IFE) for monoclonal gammopathy
B12, FA, Megaloblastic profile (Homocysteine and Methylmalonic acid)
Muscle activity
Brody's syndrome: ATP2A1
Cramps: Benign
Myotonia Congenita
Dominant (Thomsen): CLCN1 (Cl-)
Recessive (Becker): CLCN1
Acetazolamide responsive: SCNA4
Myotonic Dystrophy 1: DMPK, CTG rep
Myotonic Dystrophy 2: ZNF9, CCTG rep
Paramyotonia: Na+ channel (SCNA4)
Periodic paralysis, Hyperkalemic
Schwartz-Jampel: Perlecan
Neural & Spinal activity
Muscle pain
Myositis: + Connective tissue dis
Polymyalgia; Rhabdomyolysis
Infections: Trichinosis; Brucellosis
Myoadenylate deaminase ê (< 2%)
Myopathy +: Tubular aggregates;
Focal ê mitochondria
Drugs: Azathioprine; Steroid ê...
Rule out:
Small fiber neuropathy; Phlebitis
Bone & joint pain; Muscle Ischemia
Myasthenic Syndromes
Acquired MG: Immune ± Thyroid or Thymoma;
Childhood; Drug-induced; Neonatal Transient
Lambert-Eaton myasthenic syndrome (LEMS)
Congenital & Familial:
Familial infantile (ChAT; 10q11)
ê Synaptic vesicles & Quantal release
Congenital Lambert-Eaton-like
Synaptic: AChE deficiency (ColQ; 3p25)
Postsynaptic: AChR a b d e; Rapsyn; Plectin
AChRs: Kinetic D & ê # @ NMJs
Slow AChR channel; ê Channel open time
AChRs: Kinetic D & Normal # @ NMJs
é Conductance & Fast closure of AChRs
ê ACh-affinity & Fast-channel
AChRs: ê #s @ NMJs & Kinetic WNL
Rapsyn (11p11): ê AChRs @ NMJs
Plectin (8q24)
Other syndromes: Familial limb-girdle;
Benign congenital MG & Facial malform
Congenital LEMS-like; Familial immune
Hereditary: Glycogenolysis; CPT II;
Malignant Hyperthermia; Central core
King-Denborough; DMD (Some)
ê K+: Licorice; Li; Thiazide;
Amphotericin; Laxative
Infections; Mitochondrial; Trauma
Muscle: Ischemia; Overactivity; PM
Neuroleptic malignant syndrome
Drugs: Heroin; Phencylidine; e-ACA
Clofibrate + Renal failure;
Cyclosporine A + Lovastatin
Toxins: Venoms; IV drugs
Oral: Haff; Mushrooms; EtOH
Neuropathy 1
Axonal (idiopathic acute one such as porphria, lead, alcohol, amyloidosis, carcimatous sensory neuropathy, glue sniffing, they are axonal involving more PP Temp if severe enough may exhibit sec demyelination)
vs Demyelination Position Vib impairment (GBS, CMTs, HSMLPP, Diptheria (toxin inhibit myelin synthesis), Paraprotein (either IgM gammopathy or secondary to solitary myeloma), Refsum, Tangier, Metachromatic leukodystrophy, CIDP, MMN c Conduction block ( a Varient of CIDP that respond to IVIG and IS but not CSs or plasma exchange)
<in demyelination there is weakness s wasting, global areflexia c/t ankle areflexia in axonal>
Acute vs Subacute vs Chronic
Sensory(paresthesia spontatenous unpleasant sensation, dysesthesia unpleasant sensation d/t painful stimuli, allodynia painful sensation to unpainful stimulus) vs Motor (fasiculation, cramp, myokyma) vs Autonomic (impotence, anorgasmia, lack of vaginal lubrication, dyspareunia, heart dysrrythmia, GI early satiety,postprandial fullness, dia or constipation, urinary frequency)
Small fiber (pa/te + auto in DM, Etoh, Amyloidosis, Paraprotein, vasculitis, 33% idiopa) vs Large fiber (position/vibration) (B12 def, Sensory neuronopathy in Sjoegren or paraneoplastic ganglionopathy

Neuropathy 2
Most PN are CASSD PN
Demyelinating PN- AIDP, CIDP, MMNCB, MADSAM, DADS, Gammopathy, Diphteria, Toxic, CMT
Motor PN- AIDP, Lead, Porphyria,CMT
Acute PN- AIDP, Porphyria, Diphteria, Toxin/Drugs, Tick paralysis, Vasculitis, DM
Proximal PN- AIDP, DM Amyotrophy (DM LS Plexupathy), Porphyria
DRG Sensory Neuronopathy- Paraneoplastic, Sjogren, Syphilis, B6 intoxication, Friedreich ataxia
Asymmetric- mononeuritis multiplex, asymmetric CIDP, superimposed neuropathy or entrapment neuropathy.
Neuropathy 3
W/U (Do the right things not everything)
- CHECK Urine- Glu, Pro, BJ Pr
- 3h OGTT
pt gets 70 gram ofglucose, venus blood sample obtained, several scenarios (at 2h normal<140, 140-200 IGTT, >200 DM)
GestationalDM 105, 1h 190, 2h 165, 3 h145
Impaired Fasting 110-126
>126 DM
- B12 FA Megaloblastic profile (homocysteine, methylmalonic acid if B12 borderline value)
- Check B1, B6, B12 or Vitamin E for sensory ataxic neuropathy esp after gastric intestinal bypass surgery
- TSH, FT4
- SPEP, IFE, UPEP, if M pr do bone survey and HemOnc consult for lymphoproliferative disodeers
- Heavy metal screening
- anti RO anti La for Sjogren (anti SS-A, anti SS-B, only 10-15% ab positive, need lip bx)
- ANCA for Wegner
- Hepatitis profile
- CSF ace and electrophoresis
- Serum ACE
- LP (if suspect demyelinating or inflammatory/infectious PN) check for cell glu pr Oligoclonal band MBP IgG index
- HIV, HTLV1, Lyme
- Malignancy CXR, Anti Hu, anti Yo=Purkinje cell Ab, Anti Ri
- CT of chest abdomen for carcinoma lymphoma or solitary myeloma (skeletal survey, pelvic US)
- mamography, PET
- Autoimmune antiGliadin tests for Sjogren (salivary flow rate, Schirmer's test Rose Bengal test, labial gland biopsy)
- anti Sulfite or SGPG if senosry ataxic
- anti MAG (varient of CIDP, associated c IgM gammopathy, in elderly c significant sensory ataxia, in NCS causing prolonged DL oyt of proportion to other abn); Anti GM1 in MMN c CB, Anti GQ1b in MF varient
- CMT Panel for Hereditary-
PMP22 duplication CMT1a
MP0 for CMT1b (more severly affected, axonal form)
PMP22 deletion HSNPP
Connexin 22 for CMTx no male to male transfer
Skin Bx- only for evaluation og small fiber neuropathy
Sural nerve Bx- only if you suspect vasculitic neuropathy because most PN are chronic axonal and changes are not specific
Neuropathy 4
Foot care
Ankle care AFO ankle foot orthoses
weight reduction
sensible shoes, boots
stick, crutches walking frame
PT/OT for evaluation and equipment needs
Pain management with
Carbamazepin or Trileptal
Opiod for short term severe pain or for disabling resistant chronic pain
Oxycontin or Fentanyl patch
about 25% up to one third of polyneuropathies especially chronic axonal sensory neuropathy is cryptogenic or idiopathic. and treated with symptomatic treatment.
- Peripheral neuropathy acute aggressive treatment
IVIG 0.4 mg/kg/day x 5 days or 1 gram/kg/day x 2 days
Plasmapheresis for 5 days qod
- If DM CIDP or DM demyelinating polyneuropathy IVIG
- If bx showes autoimmune or inflammatory CS and IS
Dr. Cheema compound cream
Lidocaine 5% + Ketoprofen 5% or 10%+ Flexeril 5% disp=60 gm
use topical bid
Lidoderm patch
NM Antibodies
- Anti MAG in distal ataxic NP
- Anti GM1 in MMN c CB
- Anti GQ1b in MF form of GBS
- Anti GQ1d in GBS
- Anti Hu(or ANNA-1) in paraneoplastic sensory neuropathy or dorsal ganglionopathy neuronopathy
- Anti GAD (glutamic acid decarboxylase) in stiff person synd.
- Anti purkinje or anti Yo cerebellar degeneration
- Antivoltage gate Ca in LEMS
- Anti-CAR antibodies stain the inner and outer segment layers and the outer nuclear layer of the retina. These antibodies react with the 23-kd calcium-binding protein recoverin, which functions in the light adaptation process associated with the phototransduction cascade and initiated by light activation of rhodopsin. Cancer-associated retinopathy (CAR) occurs in patients with small cell lung carcinoma, melanoma, breast carcinoma, and a variety of gynecological tumors.
ABs in MG
1- AChR binding ab
most common ab in 87% of generalized MG and in 71% ocular MG and in 81% of all MG pt in remission. its absence make dx of MG unlikely
2- AChR blocking ab
in 40% of MG pt and correlate c disease activity. muscle relaxants cause false positive result
3- AChR modulating ab
cause endocytosis of ACh receptor and inc degradation. with binding ab they present in 90% of pt. 1-2% of MG pt have only modulating ab
4- Striate muscle ab
in 80-90% of MG c thymoma
in 30% adult MG
in 20-25% pt s clinical evidence of MG
Ab can be against Na, K, Ca channels, ACh receptors and MuSK muscle specific kinase. MuSK is candidate for seronegative MG.
MG 85% seropositive 7% MuSK positive 8% seronegative.
OH drop 10torr in DBP 20torr SBP
reverse volume depletion,anemia, meds effect
if no HR inc in favor autonomic insufficiency
Tx- 2 liter fluid, 200 mg sodium, abstain from etoh, thigh high tedhose, small carb meal
Fludrocortizone 0.05-0.3 mg bid
Midodrine a agonist 5-10 mg up to 40 mg/day (supine HTN, pruritus)
Clonidine a2 agonist
- nociceptive vs neuropathic
- source of stimulus inside nervous system vs outside
- porportinate to stimulus vs out of proportion
pain fibers- unmy c fiber (slow sustained pain), slightly myelinated A delta fiber (reflex withdraw)(Abeta mechanoreceptor Aalpha proprioception)
Pain neurotransmitters- Glu mainly, sub P, calcitonin gene related pr
- Balm
- AEDs
- Ultram
- Neurontin work through GABA rec best
- Lamictal Na CB
- Keppra not well known best
- Tegretol
- Topomax NaCB
- Gabatril GABA Agonist
- Trileptal Na CB
- Zonosemide

Paraneoplastic syndrome
- cerebellar degeneration anti purkinje or anti Yo
- anti Hu in dorsal ganglionopathy neuronopathy
- antivoltage gate Ca in LEMS
Paraneoplastic synd-
Cerebellar degeneration
Dorsal neuronopathy
Limbic encephalitis
cancer-associated retinopathy CAR
Opsoclonus-myoclonus synd c neuroblastoma the most common extracranial solid tumor in kids
Paraneoplastic syndromes predominantly affect the brainstem, cerebellum, dorsal root ganglia and medial temporal lobe.
Paraneoplastic cancer-associated retinopathy (CAR) occurs in patients with small cell lung carcinoma, melanoma, breast carcinoma, and a variety of gynecological tumors. Anti-CAR antibodies stain the inner and outer segment layers and the outer nuclear layer of the retina. These antibodies react with the 23-kd calcium-binding protein recoverin, which functions in the light adaptation process associated with the phototransduction cascade and initiated by light activation of rhodopsin.
Limbic encephalitis- dementia, sz, psychiatric symptoms associated with T2 signal changes in limbic area.
affected pt are withdrawn occ agitated.
one form could be associated with paraneoplastic chorea involving BGanglitis and they have collapsin related mediating protein 5 -CRMP5- positive Ab.
Periocular without EOM Weakness
Dystrophies: Myotonic;
FSH; Oculopharyngeal
Myasthenia Gravis (MG)
Congenital Myopathies
Rule out: VII nerve lesion
Periodic paralysis
Hyperkalemic periodic paralysis and paramyotonia congenita are associated with mutations in the gene coding for the alpha subunit of the skeletal muscle sodium channel. About 70-80% of patients with the clinical diagnosis of Charcot-Marie-Tooth disease type 1A have a region of DNA duplication on chromosome 17; deletion of this same region is associated with hereditary neuropathy with liability to pressure palsies.
Piriformis syndrome
Posterior column diseases
B12 def, HIV (vascular myelopathy), TD, herpes
Posterior and lateral columns are selectively damaged in vitamin B12 deficiency and HIV vascular myelopathy. Tabes dorsalis results in posterior column dysfunction.
Nitrous oxide abuse interfere c vit B12 dependent conversion of homocysteine to methionine causing myeloneuropathy similar to B12 def.
Posterior neck weak
Common: MG; PM; ALS
Focal myopathy: Neck; Paraspinous
Rare: FSH dyst; LMN synd; IBM;
Rod; PROMM; Acid maltase; ê K+
Carnitine; Endocrine; Desmin
Posthereptic neuralgia
acute vs chronic >3 months
nocioceptive vs neuropathic
dormant infection in DRG
Prehereptic neuralgia- 7-21 days before rash dermatomal pain
Zoster sine herepte- segmental/dermatomal pain like radiculopathy, can be associated c motor weakness, rash
PHN- pain >3 months after initial rash, cause of pain nerve damage
incidence inc with age
In first 1-3 days for vz infection acyclovir, valaciclovir, famciclovir
For pain neurontin, tegretol, DPH, Ultram, Elavil
Neuro manifestation of VZV
Skin superinfection, Pneumonitis esp in pregnancy,
- Aseptic M
- Cerebellitis ataxia, Encephalitis
- Transversemyelitis, GBS
- Pediatric vasculopathy Stroke (post varicella angiopathy may account for third of peds stroke)
- RHunt syndrome
PCR pos in CSF for VZV
role of IV acyclovir in above sever situations maybe appropriate.
Proximal arms weak
Dystrophy: Scapuloperoneal; FSH
Absent muscles; Shoulder joint D
MG; Neuropathic: ALS; P-LMN;
Brachial plexopathy
Quadriceps weak
Myopathy: Becker; Ring fiber
Myositis: IBM; Mitochon; Focal
Nerve: Femoral; LS plexopathy;
Diabetic amyotrophy; L3-L4 root
Respiratory Failure
Myasthenia gravis
Myosin-loss myopathy
Acid Maltase
Amyloid; Desmin
Polymyositis (Jo-1)
Congenital Myopathy:
Rod; Centronuclear
Neural: Phrenic lesions
Arnold-Chiari; Churg-Strauss
Brachial plexopathy; ALS
Spastic paraparesis
familial vs acquired
familial spastic paraplegia
SCA (Joseph Machado)
Slow growing tumors of spinal cord
Infectious myelopathy, HTLV1, Tropical spastic paraparesis
Tethered cord disease
Vitamin E defieiency
Friedrich's Ataxia
adrenomyeloneuropathy (adult onset form of adrenoleukodystrophy which is xlinked and d/t defective beta oxidation of VLCFA)
Statin myopathy
some they have myalgia
10 percent prevalence
other drugs toxic
nefazodone gemfirozil cylosporin etoh exercise verapamil diltiazem
grapefruit pomegranite juice

Chinese red rice yeast 2 tab hs cause 17 percent reduction
try lipitor or rosuva biw
tonic water quinine, q10
pulse therapy with
Stiffman syndrome
etio- autoimmune or paraneoplastic (breast cancer)
anti GAD (+ in 60-70%), anti amphysin, geyhertin
clinical- prox stiffness, hyperlordosis, DM, Autonomic instability, fear of open spaces, myoclonus
some pt may have only one leg stiffness eg after R knee injury.

EMG- continous spontaneous MUAP discharge esp in thoracolumbar paraspinal
Labs- check for neoplasm CXR, Mamography, prostate
- spasticity from myelopathy, MS, brain stem tumor, motor neuron diseases
- spondylosis
- fibromyalgia
- myotonia
- proximal myopathies
- dystonia
pt diary for no of episodic spadm
symptomatic vs immunologic
- BNZD diazepam average dose 20-40 mg/day, clonazepam, alprazolam
- AEDs
VPA, vigabatrin, tiagabine up to 6 g/d, gabapentin 3600 mg/d
- Botox, Myoblock
- Baclophen pump
- clonidine inhibit NE release
- CSs varying degree of improvement
- Immuran, Cellcept, cyclophosphomide
- Plasmapheresis less than 15% benefit
- IVIG was effective in NIH study NEJM Dalakas 2000,345:1870
Prognosis- stabilize in several year they may need baclofen pump or IVIG. they have normal longevity like general dystonia
Diazepam is the mainstay of treatment for the stiff-person syndrome, which occurs about as often in women as in men. Onset in adult life, proximal distribution of stiffness, development of lordosis, and precipitation by motion or emotion are typical. Diabetes and organ-specific autoimmune disorders are common. Seizures sometimes occur.
Stiff-person synd has a plus varient called progressive encephalomyelitis with regidity PER
GAD65 Antibody act against GAD rate limiting enz for GABA synthesis results in alpha motor neuron hyperactivity.
Wasting > Weakness
Pathology: Type II atrophy
Cachexia: Wt loss > 15%
Disuse; Steroid myopathy;
Paraneoplastic; Aging
Weakness > Wasting
Polymyositis; Myoglobinuria;
Periodic Paralysis;
Myasthenia gravis;
Neuropathy with conduction block
Neuromuscular CIDP 1 CIDP
Varients of CIDP
Temporal-SIDP, Relpsing GBS
Regional-DADS, MADSM, Paraparetic CIDP, CNeuropathy
Functional- motor, sensory, ataxic CIDP
1) clinical course->8w, relapsing remiting
2) CSF pr>45 in DM CIDP>100
3) NCS/EMG sample 4 nerves (inc DL and F wave, dec CV, CB and temporal dispersion)
4) Nerve bx
EMG Criteria
- 4 nerve sample, 3 should be abnormal
- CB TD in 1, f dl cv in 2
- f dl cv in 3 in abcense of cb td
- f dl cv with positive bx
cb drop 20% in p-p amp or area
td 0.9 ms

- Idiopathic
- Monolonal gammopathy, MGUS, POEMS, lymphoma
- Autoimmune: SLE,RA,Sjogren,Sarcoidosis, thyroid, MG
- Infection: HIV, HTLV 1,hep b c
- transplantation, vaccination
- malignncy
- meds eg procainemide, inf alpha
pt c DM CIDP
- prominant prox or generalized weakness
- progressive course over a few months
- conduction block not in entrapment sites and other NCS findings
- CSF Pr>100
- Response to therpeutic trial of IVIG or PE
- DM LS radiculoplexopathy might share pathologic features of DM CIDP
Lab w/u
- SPEP, IFE serum, urine
- M pr 1.5 - 3 g/dl MGUS
- M pr >3 g/dl malignant plasma cell disorder
also check for cryoglobulins, B2 microglobulin, serum viscosity, bone scan, BM bx
- Skeletal bone survey for osteosclerotic myeloma and POEMS esp if IgA, IgG or lambda light chain monclonal gammopathy. Sometimes CT of thorax and abd is necessary to rule out lymphoma
- if suspecious ANCA, RF, ACE, anti SSA-SSB, Hep B and C, HTLV1, Lyme serology
- if suspect or younger than 40, genetic study for CMT type 1A,1B and X, HNLPP
- CSF pr >45, cell should be <10, fewer than 50 in HIV cases
if CSF pleocytosis check for HIV, lyme, lymphomatous meningitis and sarcoidosis

- other immune mediated neuropathy
- toxin meds, glue sniffing, aresnic poisoning, amidarone
- IgM MGUS neuropathy or DADS
distal, predominantly sensory, prolonged DLIndex, lack of response to CS, associated with anti-MAG or anti-GD1b
- MMN c CB
Neuromuscular CIDP 2 CIDP Tx
Goals: reduce symptoms (weakness, sensory loss, ataxia, pain), improve functional status, long term remission
- Use PT/OT cane, walker, AFO
First line tx: CS,IVIG,PE
If elderly with steroid complication use Steroid sparing agents (Imura, Cyclosporine A, Cellcept etc)
- 1/3 not respond to conventional therapy and have axonal loss on EMG, use prednisone plus PE or IVIG monthly, if no improvement add cyclosporine or monthly IV cyclophosphamide
1to 1.5 mg/kg/d takes 2w to 2m to show effect
taper by 5-10 mg q2or4 week
monthly pulse metylprednisolone or oral dexamethasone
Steroid side effects
Acute: mood lability, insomnia, fluid retention, steroid psychosis
Chronic: check PPD, weight gain, DM,cataract, glucoma, gastritis, osteporosis, vertebral fx, aseptic necrosis of femoral or humeral head,
steroid myopathy, impaired wound healing, increased infection (herpes zooster, cutaneous fungal infection, TB reactivation, recurrent pneumonia), hirsutism, cushingoid state, pseudotumor cerebri

0.4 gram/kg qd x 5 days or 1gram/kg qd x 2day over 4-6 hours
infuse slower in pt with CHF, RF, vascular disease or elderly
- check IgA, CMP, CBC before
- For HA, Flu like pretreat with 60 mg Solumedrol IV and for fluid overload infuse slower esp in elderly
- Contraindications hypotension, coagulopathy, thrombocytopenia
- administer NS 1 lit several h before PE reduce risk of hypotension and vasovagal response
- a single PE remove 3-5 lit of plasma and reduce IgG by 45% and 5 PE reduce igG by 90%
- 5 PE 250ml/kg qod times 5
- PE complications
CVC access pneumothorax, site infection, venous thrombosis
Then dec BP, dysrrhythmia, vasovagal response, citrate toxicity with NV and carpopedal spasm (hypocalcemia), muscle cramp, paresthesia, allergy to infused plasma, anemia, bleeding, infection
Neuromuscular CIDP 3 CIDP Tx2
- pt not improved with above
- improved but has frequent relapse
- intolerable side effect to CS
- takes 4-6 m to see effect
Mycophenolate Mofetil (Cellcept)
- inhibit purine nucletide synthesis, dec proliferation of B and T cells
- IS c/t Azathioprine with less BM suppression
- Dose 500 mg bid to increase by 500 mg q2w to 1000 mg bid, check CBC and CMP
- SE include NV,HA, tremor, leukopenia, dec platelets, inc inf,potential for developing lymphoma and other malignancies
Azathioprine (Imuran)
2-3 mg/kg/day
- Start 50 mg qd first week and then inc by 50 mg qweek to max dose
- Check CBC,LFTs qweek x 4 then monthlyx4 then q3months
- Avoid in WBC<1000, Platelet<50000, with Allopurinol (dec dose by 1/2 or 1/3) and ACE I (inc risk of leukopenia)
- Avoid pregnancy up to 6 months after discontinuation of drug
- SE include inf, neoplasia, inc LFTs, rassh, alopecia, arthralgia, pancreatitis
Cyclosporine A
-5mg/kg/day PO in 2 divided dose bid
- Keep trough level 100-200 ng/ml
- Adjust the dose by 1mg/kg/day if Cr inc by 50% or above 2, SBP>150 or DBP>90, Higher trough level, dose adjustment should not occure more frequently than q4w and nore tan 1mg/kg/day
-SE include RF, HTN, Hirsuism
-PO or monthly IV
- PO 2mg/kg/day
- IV 1 gram/m2 monthly
- SE NV (give zofran) BM supression, Alopecia, Hemorragic cystitis (check UA and CBC every 2 weeks), teratogenic effect, infertility
- Give drug holiday for 3-6 months if they are taking PO for 12 months or IV for 6 months
INF alpha2a 3 million IU SQ tiw
INF Beta1a 3-10 million IU SQ tiw
INF Beta1a 30 ug IM qweek
Neuromuscular EP Evoked potentials normal values


Median somatosensory EPs
Neuromuscular EP Median somatosensory evoked potentials in cervical spondylosis may show diminished amplitude of N13. Arnold-Chiari malformation is associated with normal amplitude of N13 and increased N13-N20 interpeak latency. In amyotrophic lateral sclerosis, median SEP's are typically normal.
In BAEP's, absence of wave I with intact wave V is most commonly due to peripheral hearing loss. wave V impaired in inf colliculus.
Chiappa KH. Evoked potentials in clinical medicine. 3rd ed. New York: Raven Press, 1997.
A unilateral P100 abnormality indicates an ipsilateral lesion of the visual pathway anterior to the optic chiasm such as a unilateral demyelinating process or optic nerve glioma. A tumor of the occipital lobe or a thalamic hemorrhage would cause a bilateral abnormality or little or no effect on the P100 latency.
The N13 potential is generated at the cervical cord level, and an absent response would suggest a lesion involving the cervical cord.
Somatosensory evoked potentials can be elicited in the absence of a recordable peripheral sensory nerve action potential because the CNS can amplify the incoming responses.
Neuromuscular Limb-Girdle dystrophy Limb-Girdle dystrophy
- AR or AD
- difficulty reaching high objects or climbing stairs
- scapula winging
- ddx from fasciscapulahumeral FSH dystrophy, they have scapula winging, can have foot drop.

- cbc, cmp, la, cpk, aldolase, esr, ana, tsh, ft4
- emg
- genetic test Aethena
genetic consult
- check heart echo
- muscle biopsy
- pt/ot for walking
- check for other myopathies eg mitochondrial, metabolic, inflammatory, congenital, meds induced myopathies

Neuromuscular Myasthenia MG Abs
1- AChR binding ab
most common ab in 87%of generalized MG and in 71% ocular MG and in 81% of all MG pt in remission. its absence make dx of MG unlikely
2- AChR blocking ab
in 40% of MG pt and correlate c disease activity. muscle relaxants cause false positive result
3- AChR modulating ab
cause endocytosis of ACh receptor and inc degradation. with binding ab they present in 90% of pt. 1-2% of MG pt have only modulating ab
4- Striate muscle ab
in 80-90% of MG c thymoma
in 30% adult MG
in 20-25% pt s clinical evidence of MG
Neuromuscular Myasthenia MG DDx
in lems more autonomic sx eg dry mouth impotence,more prox muscle weakness hip shoulder girdle, less ocular sx ptosis diplopia
loose reflexes earlier than MG
LEMS can be associated c cerebellar ataxia d/t Ca ch. IgG against purkinje cells.
*Myotonia fluctuans- EOM Myotonia as well trunk, limbs fluctuating daily, warming up usually relieves symptoms. EMG shows myotonia, muscle biopsy normal, DNA analysis shows mutatio in Na channel. Tx acetazolamide, mexilitine to relieve stiffness.
* Neuromyotonia, cramp/fasiculation syndrome associated c K ch. ab implicated c Limbic encephalitis, Morvan disease and peripheral nerve hyperexcitibility
If can not get knee reflexes do knee ext and b/o facilitation phenomenon u can get knee reflex, no facilitation in MG
increment response from 2 Hz 50 Hz stimulation b/o facilitation
- cerebellar degeneration anti purkinje or anti Yo
- anti Hu in dorsal ganglionopathy neuronopathy
- antivoltage gate Ca in LEMS
Paraneoplastic synd-
Cerebellar degeneration
Dorsal neuronopathy
Limbic encephalitis (K ch. ab implicated c Limbic encephalitis, Morvan disease and peripheral nerve hyperexcitibility)
Paraneoplastic syndromes predominantly affect the brainstem, cerebellum, dorsal root ganglia and medial temporal lobe.
usually we treat LEMS same as MG
ab evalution- ca ch. blocker
achr blocking ab (most important correlate disease activity), smooth muscle ab , achr binding ab (most common), achr modulating ab, striated muscle ab,
3,4-diaminopyridine (3,4,-DAP) blocks a K+ channel and increases acetylcholine release. It has been used for treatment of Lambert-Eaton myasthenic syndrome.
dose 0.5-3.5 mg/kg/day po in 2-4 divided dose. may be wrong dose usuall dose 5-10 mg tid
Also use varient 4-aminopyridine for MS 5 mg tid for fatigue.
Neuromuscular Myasthenia MG DX
don't get knee ext or toe flexor
- Abs- most important Achr abs 10-15% abs neg but in these pt MUSK muscle specific kinase ab is positive.
(in general pt population 70% is positive)
- Tensilon if pt has ptosis
- RS repetitive stimulation
decremental or very minimal incremental response c/t LEMS which has significant incremental response.
- SF EMG single fiber EMG in ocular MG or when ab neg
double vision on lat gaze or ptosison upwrad gaze happen in less than 60 sec
arm stretching at 90 degree drop in less than 4 min
swalling impaired as well as fascial weakness
10% of MG are are associated with autoimmune disorders such as SLE, Thymoma, Hyper/Hypothyroidism, Pernicious anemia, DM. So need to check for these at time of dx.

Jitter on single fiber EMG can be seen with diseases of neuromuscular transmission such as myasthenia gravis as well as a denervating neuropathy such as amyotrophic lateral sclerosis.
The congenital myasthenic syndromes are not related to an immune process, but are caused by genetic defects affecting the neuromuscular junction. These include defects in acetylcholine synthesis and packaging (familial infantile MG), end-plate deficiency of acetylcholinesterase, acetylcholine receptor deficiency, and the slow channel syndrome.
The most sensitive test for myasthenia gravis is single fiber EMG of the frontalis muscle.
Neuromuscular Myasthenia MG TX
IVIG 2mg/kg
Plasmaheresis in ICU setting
IS Azathioprine (Imuran) less prednisone dose requirement but it takes about 18 months to start working, cyclosporin takes 2-4 months to start working, mycophenolate (Cellcept) may take 2 months to start working
(check for skin TB Test before starting CS or IS, also check for DM before CS)
Thymectomy for sure, emphesize on radical surgery as much as possible.
higher remission rate for thymectomy pt 2 times rate.
Not useful in pt c MUSK positive pts and pt over 60 age group b/o risk of surgery in presence of class II trials not advisable to do surgery.
Prednisone may get worse in 1-2 weeks of intiation of therapy
Mestinon symptomatic tx with Robinul (glycopyrrolate 1 mg prn 1/2 1 h before mestinon dose) to dec NVD associated c mestinon. or use long acting Mestinon
completeremission no ss without tx after 1 year
pharmacologicremission when no ss on meds for 1 year

Drugs safe in MG
Bromocriptine, chloramphenicol, prozac, gabapentin, ACE I
Drugs cotraindicated
CaCB, Beta B eg inderal
Aminglycosides, polymyxins,
procainamide, quinidine,
Li, thyroid hormones
Neuromuscular Myoadenyalte Deaminase MAD deficiency
Myoadenylate deminase deficiency
- Seen in 5% of population
- Can cause Statin hypersensitivity
- Can be diagnosed with enzyme assay (muscle biopasy and enzyme staining by histochemistry) or IFET or genetic test for AMPD1 gene mutation, common form is C34T
Ischemic Forearm Exercise Test (IFET)
- Can dx glycogen storage disease, mitochondrial disorders and MAD deficiency
- Pt should be fasting , 30 min rest, lay supine
- Draw blood from the antecubital vein of the ipsilateral exercising arm
- Before and 10 min after sustained ischemic hand grip
- Inflate BP cuff 30 mmhg above SBP and ask pt to do forceful forearm and hand grip excercise (can use hand grip dynamometer from Jamar Inc, Bolingbrook, IL)
- Check for lactate and ammonia, lactate should inc and
- Complications: forearm compartment syndrome or rhabdomyolysis
Mechanism: if you can't metabolize glucose you go to the anerobics and Pr breakdown pathways
MAD in Pr breakdown causing ammonia production
Glycogen storage/Glycolytic disease:
decreased lactate rise, Normal to inc Ammonia rise
MAD Def: Normal lactate rise, Decreased Ammonia rise
Mitochondrial disorders: Inc lactate and ammonia at baseline fasting,

Neuromuscular Myopathy Deuchenne
abscence of dystrophin inc utrophin (in nm junction) dec sacroglycan
(immunostaining also performed for merosin def, dysferelin for LGMD)
geneic test 70% deletion rest of them point mutation
- weight control, speech therapy, assistance c learning difficulties
- Pulmonary care, annual flu shot, overnight sleep study for nocturnal hypoventilation esp when VC reach <60%, cough assistance for mucocilliary clearance
- at age 10-12 Cardiology evaluation
- Orthopedics >25%-35% scoliosis
- Supportgroups
- MV
- Calcium supplement
- Steroids
prednisone 0.75mg/kg/day
check k(def eat banana) cbc cmp TB Skin test, CXR (as baseline as well as TB),
- warn about behavioral side effects as well as obesity, DM, PU
may improve muscle weakness a little bit
Oraped (prednisolone oral syrup)15 mg/5ml better tolerated
- check BP after 2 weeks
- check for indigestion pu if anyproblem reported start Zantac
(steroids may work for Becker)
Deflazacort (0.9-1.2 mg/kg/day)has less SE available in Canada or Mexico but Cataract more common vs prednisone
Creatine monohydrate 5-10 gram/day may improve strngth inc muscle supply of phophocreatine inc ATP resynthesis
NSAIDs or COX2 inhibitor may work.
by definition ss start before age 5
Becker by definition still ambulatory at age 16
in DMD they can have smooth muscle involvement eg gastric bladder dilation, mild dec IQ, hypertrophic cardiomyopathy cor pulmonale
pseudohypertrophy can also be seen in vastus lat, deltoid
in FSH in contrast to LGMD, deltoid is always spared.
hp, incCK, myopathic EMG, Bx immunestaining (dystrophin ab staining)
DMD <3% dystrophin BMD >20% dystrophin
female can also get DMD, b/o x random inactivation, XO Turner synd
Future tx
gene (micro mini gene) therapy
stem cell therapy
up regulation Utrophin
myoblast implantation
more effective meds
Neuromuscular Myopathy Extraocular muscles weak
Myasthenia Gravis (MG)
Thyroid; Botulism
Mitochondrial: KS; PEO; MNGIE
Centronuclear; Multicore
Oculopharyngeal MD; IBM + Contracture
Oculopharyngodistal myopathy
Congenital ophthalmoplegias
Neuromuscular Myopathy Inclusion body myositis produces a characteristic pattern of weakness involving finger flexor and quadriceps muscles most severely. Muscle enzymes are normal or minimally increased, and EMG studies typically reveal an inflammatory myopathy. The muscle biopsy finding most typical of inclusion body myositis is vacuole formation surrounded by a basophilic rim.
Critical care myopathy is an under-recognized disorder characterized by selective loss of myosin from myofibers. Also known as myosin losing myopathy, this disorder is most commonly seen in critically ill patients treated with corticosteroids and neuromuscular blockers.
Drug-induced muscle disorders include myalgia, myotonia, type 2 atrophy (e.g., prednisone,MG), and focal (e.g., oxycodone), necrotizing, inflammatory (e.g., L-tryptophan), mitochondrial (e.g., zidovudine) or autophagic (e.g., amiodarone) myopathies.
Mastaglia FL, Laing NG. Investigation of muscle disorders. J Neurol Neurosur Psych 1996;60:256-274.
Which myopathy can cause ptosis-
mitochondrial myopathy
in old ages ocilopharyngeal muscular dystrophy
myotonic dystrophy stiner disease
Deuchenne tx
prednisone 0.75mg/kg/day
check k cbc cmp TB Skin test, CXR, warn about behavioral side effects
may improve muscle weakness a little bit
Hypothyroid myopathy is commonly associated with painful cramps and impressive elevations in serum CK levels. Muscle percussion commonly results in a slow, prolonged, electrically silent local mounding called myoedema. Polymyositis is not typically accompanied by painful cramps.
Paramyotonia congenita
ch 17q23.1 muscle Na voltage gated channel defect. major symptom orbicularis oculi myotonia on exposure to cold.
Neuromuscular Myopathy Muscle biopsy
findings reflect the underlying biochemical abnormalities. In carnitine deficiency, there is a defect of transport of fatty acids into the mitochondria, and lipid therefore accumulates in the muscle. Myophosphorylase deficiency impairs carbohydrate utilization leading to accumulation of glycogen. In mitochondrial myopathies, subsarcolemmal accumulations of numerous malformed mitochondria are seen as red accumulations on the modified Gomori trichrome stain ("ragged red fibers"). Inclusion body myositis is an indolent myositis of late adult life characterized by rimmed vacuoles in muscle fibers best seen on cryostat sections. Ultrastructurally, filamentous whorls are seen within the rimmed vacuoles.
abn Z band in nemaline myopathy
Neuromuscular Myopathy Myotonic dystrophy
AD Ch. 19, c variable penetrance anticipation, triplet repeat
SS- frontal balding, temporal /master wasting, elongated faces(sad face)(hatchet face, fish mouth appearance), thin neck (SCM Atrophy)
distal weakness c/t prox weakness in other myopathies, myotonia in hands (grip myotonia)or tongue, percussion myotonia over thenar eminence that dimples and stay dimpled for several seconds, or when shaking hands difficult letting it go.
Endocrinopathies, dec T4, testicular atrophy, inc Insulin, DM, dec GH, adrenal atrophy
Cardiomyopathy check EKG, Echo
Inc Aldolase, CPK minimal
inc TG, Cholestrol
Dysphagia speech
Dyspnea PFT Procainamide
EMG myotonia waxing waning MUP, myopathic potentials, involvement of large fiber motor/sensory fibers
Aethena myotonic dystrophy panel
mexilitine, procainamide (250 mg qid), DPH (Na CB), CBZ for myotonia, quinine or tocainamide also suggested but maybe more toxic
- if K sensitivity is demonstrated acetazolamide may be used
AFO Wrist splint for foot/wrist drop
Neuromuscular Neuropathy Dorsal root ganglia/sensory neuronopathy/ganglionopathy
Chronic active hepatitis
Rickettsia conorii infection
Vit B6 or E def
*Paraneoplastic (anti Hu ab)
*Sjogren (ANA,RF,SSA or anti Ro,SSB or anti La)
Abx related (4-12 days after Abx)
Thalidomide (when used in tx of skin diseases or leprosy)
Neuromuscular Peripheral nerves CMT
Hereditary Neuropathies
demyelinating, CV around 20 m/s
axonal (dec CMAP, CV around 30s)more leg involvement, inverted champagne leg MPO mutation
no male to male transmission
PMP22 deletion

PMP22 duplication CMT1a
MP0 for CMT1b (more severly affected, axonal form)
PMP22 deletion HSNPP
Connexin 22 for CMTx no male to male transfer
Neuromuscular Peripheral nerves heavy metal poisoning
A heavy metal screen tests for chronic heavy metal poisoning and exposure, and the test is almost always done on urine. Blood screening for heavy metals, such as arsenic, is done only for the uncommon situation where acute poisoning is suspected. Since arsenic is rapidly removed from blood, blood is not the specimen of choice to rule out chronic arsenic exposure. The heavy metal screen will almost always include tests for lead, arsenic, and inorganic mercury, but toluene and methanol are not heavy metals and must be analyzed by separate methods. Organic mercury poisoning is a unique situation where tests need to be done on whole blood since this form of mercury is mainly located in erythrocytes.
Neuromuscular Radiculopathy LOWER EXT NEUROPATHIES:
femoral vs L3-L4 radiculopathy (also involves obturator neuropathy=thigh adduction w medial thigh n) happens inpelvic injuries/surgeries or retropritoneal hematoma or pelvic mass c hip flex
knee ext weakness, loss of knee reflex and ant thigh numbness
L3-L4= femoral + obturator
sciatic neuropathy (post tibialis + common proneal) ddx stroke in foot area of motor cortex, radicuolopathy
causes-muscular or bony pressure on sciatic, post hip dislocation, acetabular fx,im injection
all foot ankle w plus knee flex w plus
loss of achilles reflex and foot lateral leg n
proneal palsy- ddx c L5 radiculopathy(distinguish from L5 radiculopathy-hip abduction <gluteus medius> should be spared in pure peroneal, distinguish from sciatic neuropathy- ankle inversion <tibialis post> and hamstrings should be spared, in other words sciatic neuropathy also involves foot inversion w as it carries out by post tibialis) ss foot drop, foot dorsiflexion eversion weakness no inversion weakness, lat leg n
causes: stretch injury by forcible
foot inversion, compression by tight stocking cast crossed leg or trauma
L5= common proneal + post tibial
Meralgia paresthetica- lat femoral cut nerve- lat thigh n no ref or
motor w
causes- obesity, pregnancy, weight loss, or heavy equipment belt wihch cause compression of nerve under femoral ligament
ddx c L2 L3 radicucause motor w or
knee areflexia
Morton metatarsalgia- tight shoes compress toes nerves esp 3 and 4 one causing patchy paresthesia

donpezil can be used in AD, Vascular dementia and mixed, MS, PD, ADHD, Closed head injury
Neuromuscular Radiculopathy Patients with spinal stenosis may have leg pain on exertion, which is relieved by rest (neurogenic claudication). This pain is worse with back hyperextension, relieved by leaning forward when walking (e.g. when using a shopping cart), and often not present when riding a bicycle. Absent peripheral arterial pulses suggests vascular claudication rather than neurogenic claudication.
Erb-Duchenne upper plexus paralysis occurs secondary to damage to the fifth and sixth cervical roots or upper trunk of the brachial plexus. It is a common deficit and is usually due to traumatic separation of the head and shoulder but may also be due to pressure on the shoulder, birth injuries, or idiopathic plexitis.
A femoral neuropathy causes quadriceps weakness with sparing of the adductors and iliopsoas muscles, absent or decreased ankle jerk, and loss of sensation of the anteromedial thigh and medial lower leg.
Neck-Tongue synd.
pain/paresthesia in half of the tongue following neck movement. sometimes c neck/occipital pain, trapezius discomfort, ipsilat hand paresthesia. getC spine MRI, cervical collar.
Neuromuscular Radiculopathy Radiculopathies
Changes in dermatome myotome or reflex changes but could be overlaping and usually dense numbness is more indicative of a peripheral nerve lesion
* structural- Musculoskeletal (disk, spondylolisthesis, spondylosis eg lig flavum hypertrophy, facet syndrome), epidural abscess, mets
* microscopic s evidence of mass lesion-
(pt has normal mri but true radiculopathy)
1) infiltration by tumor carcinomatous or lymphamtous meningitis, 2) infiltration by granulamatous tissue eg sarcoid, or 3) infection eg Lyme, herpes zooster, cmv, herpes simplex
4) inflammation eg AIDP GBS
5) infarction eg vasculitis or dm causing nerve root infarction
CT is the best imaging study for bone deformity combine with myelogram for soft tissue
CT good for >350 and pacemaker
MRI for soft tissue, MRI c s contrast useful to delinate scar from recurrent disease
CT good for >350 and pacemaker
MRI for soft tissue, MRI c s contrast useful to delinate scar from recurrent disease
If bone deformity or hardware steel ct c myelo prefered
titanium hardware you can get open mri
mri for previous surgery or tumor infection
bone scan for fx otherwise not visible like pars interarticularis
facet artheropathy
Discography only in discogenic pain may help localize orexclude a motion segment
Brachial plexus
- post cord ARTS
- medial cord ulnar medial head of median
- lat musculocutaneous lat head of median
radiculopathy intact Motor Sens NCV paraspinal involvement
nerve root avulsion intact S only NCS
brachial plexopathy impair M S NCS
mononeuropathy impair M S NCS
Neuromuscular Radiculopathy Upper ext nerve injuries-
nerve root avulsion
brachial plexopathy
* radi associated with radicular pain and abscence reflexes
* plexupathy 2 type:
upper trunk erb duchenne palsy waiter tip in traction of neonate shoulder or motorcycle accidents causes c5 c6 s s with deltoid biceps infraspinatus wrist ext weakness hand finger spared similar to c5 c6 radiculopathy or root avulsions
Tx- immobilization
PT/OT for range of motion exercise
ortho consult
EMG/NCS in3-4 months or 6 weeks
Ortho operation in 5 moths
lower trunk klumpke - grabbing something when falling from tree or thorasic outlet or pancoast tumors
c8 t1 ss mainly hand finger ext weakness and ulnar neuropathy ss ddx c ulnar neuropathy t1 numbness occ horner and
involvement of LOAF muscles
c5 vs axillary mononeuropathy-
in dislocation or fx of prox humerus
c deltoid w and shoulder n
c5 also cause biceps weakness
Radial neuropathy- sat night palsy, crutch palsy or after humerous fx-w of all ext of arm/hand/finger wrist drop loss of triceps reflex radial distribution n
subgroup trauma or pressure on post interosseous below elbow or tight wrist band or handcuff causing only numbness on back of hand (cheralgia paresthica)
Median- honeymoon palsy, fx of humerous or distal radious, preacher (orator) hand subgroup- pronator synd as nerve passes through pronator tres muscle w of pronation
cts- wrist,2&3 flexion and thenar n are spared since these nerves branch befor carpal tunnel
tinel phalen flick (shaking of hands to relieve paresthesia)
different hands-
wrist drop radial palsy
preacher (orator) hand-median palsy
claw hand- ulnar palsy
simian monkey paw hand- median and ulnar palsy
ulnar palsy- fx of medial epicondyle, restin elbow on table, leaning while cycling compresssion of ulnar nerve over hamate bone in Guyon canal of wrist or cubital tunnel synd
radiculopathy intact Motor Sens NCV
nerve root avulsion intact S only NCS
brachial plexopathy impair M S NCS
Neuromuscular Tensilon test Tensilon test
should be double blind
edrophonium cl is rapidly acting anticholinestrase that improve ptosis and oculomotor paresis. rare pt supersensitive b/o depolarization of motor endplates or abn vagal response so code tray and intubation devices should be ready at the time.
in newborns SQ 0.15 mg/kg
in infants IV 0.2 mg/kg reverse weakness within 1 minute
A lesion of the third nerve nucleus produces weakness of muscles innervated by that third nerve, but also bilateral weakness of the superior rectus, levator palpebrae, and pupillary constrictor muscles. A lesion of the third nerve itself does not affect any contralateral muscles. Thus, ptosis of the left eyelid could result from lesions of the left third nerve or either left or right third nerve nucleus. Cortical lesions have also been reported to cause either contralateral or bilateral ptosis on occasion.
The optic nerve is part of the central nervous system and, hence, its myelin is derived from oligodendroglia as opposed to Schwann cells that provide myelin to the other cranial and peripheral nerves.
Transient episodes of monocular or bilateral visual loss lasting seconds are characteristic of increased intracranial pressure and may be precipitated by changes in posture.
Anton's syndrome, the denial of blindness, is typically associated with bilateral posterior cerebral artery territory infarction producing "cortical" blindness plus memory impairment.
Adie's tonic pupils
dilated pupils nonreactive to light/accomodation
respond to very diluted 0.125% pilocarpine and dec from 7-8 mm to 3-4 mm after 30 minutes
parasympathtic denervation hypersensitivity
areflexia, common in women 20-40 yo
etiology- postviral,
no pathology in CNS
In complicated third nerve palsies where other neural
structures are involved, have the patient undergo an MRI. In isolated third nerve palsies with no pupillary involvement where the patient is over 50, MRI scanning, an ischemic vascular evaluation, and daily pupil evaluation is indicated.
If the patient is under 50 and has a non-pupillary involved isolated third nerve palsy, intracranial angiography is indicated
since ischemic vasculopathy is less likely to occur in this age group than is aneurysm. If the adult patient of any age presents with a complete or incomplete isolated third nerve palsy with pupillary involvement, consider this to be a medical emergency and have the patient undergo intracranial
angiography immediately. In these cases, the cause is likely subarachnoid aneurysm and the patient may die if the aneurysm ruptures. Children under the age of 14 rarely have aneurysms; the majority of third nerve palsies in this age group are traumatic or congenital.
Isolated third nerve palsy due to ischemic vasculopathy will spontaneously resolve and recover over a period of three to six months. If the palsy fails to resolve in this time frame, repeat the MRI to search for the true etiology.
Myasthenia gravis has the ability to mimic virtually any cranial neuropathy, including isolated third nerve palsies.
Myasthenia gravis must remain a possible diagnosis when encountering a third nerve palsy, especially when the course is variable or atypical.
Third nerve palsy results from damage to the oculomotor nerve anywhere in its course from the nucleus in the dorsal mesencephalon, its fascicles in the brainstem parenchyma, the nerve root in subarachnoid space, or in the cavernous sinus or posterior orbit. Damage to the third nerve nucleus results in an ipsilateral third nerve palsy with contralateral
superior rectus under action and bilateral ptosis. Damage to the third nerve fascicles results in an ipsilateral third nerve palsy with contralateral hemiparesis (Weber's syndrome), contralateral intention tremor (Benedikt's syndrome), or ipsilateral cerebellar ataxia (Nothnagel's syndrome). Vascular
infarct, metastatic disease and demyelinization are the common causes of brainstem involvement.
Damage to the third nerve within the subarachnoid space
produces an isolated third nerve palsy. The main causes are compression of the nerve by an expanding aneurysm of the posterior communicating artery or the basilar artery, and ischemic vasculopathy. There will always be pain in
aneurysmal compression and pupillary involvement is typical, though there have been infrequent cases of aneurysmal compression that did not initially affect pupillary function. In ischemic vascular nerve third palsies, pain is frequent and the pupil is typically normal and reactive.
Damage to the third nerve in the cavernous sinus, superior
orbital fissure, or posterior orbit is unlikely to present as third nerve palsy due to the confluence of other structures in these areas. Cavernous sinus involvement may also include pareses of cranial nerves IV, VI and V-1, and an ipsilateral Horner's syndrome. The most common causes of damage in
these areas include metastatic disease, inflammation, herpes zoster, carotid artery aneurysm, pituitary adenoma and apoplexy, and sphenoid wing meningioma.
The patient will usually present with sudden onset unilateral
ptosis (or rarely, a bilateral ptosis if the damage occurs to the third nerve nucleus), which is frequently accompanied by significant eye or head pain. The patient rarely complains of double vision because the ptosis obscures the vision in the affected eye; however, if the lid is manually elevated, the patient will experience diplopia. Acuity is typically unaffected unless damage occurs in the superior orbital fissure and cranial nerve II is also involved. The affected eye positions in a non-comitant exotropic, hypotropic position (down and out).
There will be limitation of elevation, depression and
adduction. There is an underaction of the superior, inferior, and medial recti muscles and inferior oblique muscle, which may be total or partial.
The pupil may be dilated and minimally reactive to light (pupillary involvement), totally reactive and normal (pupillary non-involvement), or may be sluggishly responsive (partial pupillary involvement). The patient is frequently elderly and often has concurrent diabetes and/or hypertension.
Third nerve palsy results from damage to the oculomotor nerve anywhere in its course from the nucleus in the dorsal mesencephalon, its fascicles in the brainstem parenchyma, the nerve root in subarachnoid space, or in the cavernous sinus or posterior orbit. Damage to the third nerve
nucleus results in an ipsilateral third nerve palsy with contralateral superior rectus under action and bilateral ptosis. Damage to the third nerve fascicles results in an ipsilateral third nerve palsy with contralateral hemiparesis (Weber's syndrome), contralateral intention tremor (Benedikt's
syndrome), or ipsilateral cerebellar ataxia (Nothnagel's syndrome). Vascular infarct, metastatic disease and demyelinization are the common causes of brainstem involvement.
The patient will present with complaints of vertical diplopia,
which is especially manifest as the patient tries to read. There may be an
inability to look down and in. There may also be horizontal diplopia, as a
lateral phoria occurs due to the vertical dissociation. The patient often
has a head tilt contralateral to the affected superior oblique muscle. The
chin is often tucked downwards as well. There is frequently concurrent
hypertension and/or diabetes. The patient will present with a hyperphoric or
hypertropic eye on primary gaze. On alternate cover test, the
hyper-deviation will increase in contralateral gaze, reduce in ipsilateral
gaze, increase on ipsilateral head tilt, and decrease on contralateral head
tilt. Visual acuity is unaffected and there is very rarely pain. In
bilateral cranial nerve IV palsy, the patient will manifest a
hyper-deviation which reverses in opposite gaze.
The fourth cranial nerve nucleus is located in the dorsal
mesencephalon. From here, the nerve fibers then decussate and exit the brain
stem dorsally into the subarachnoid space. The nerve then courses around the
brain to enter the cavernous sinus, superior orbital fissure, orbit, and
innervate the superior oblique muscle. Damage to the fourth nerve nucleus or
its fascicles within the brain stem will give a contralateral fourth nerve
palsy, along with the associated signs of light-near dissociated pupils,
retraction nystagmus, up-gaze palsy, Horner's syndrome, and/or internuclear
ophthalmoplegia. Bilateral fourth nerve palsies are possible as well. The
main causes of damage to the fourth nerve in this area are hemorrhage,
infarction, trauma, hydrocephalus and demyelinization.
The fourth nerve is especially prone to trauma as it exits
the brain stem and courses through the subarachnoid space. In contrast to
third nerve palsies within subarachnoid space, fourth nerve palsies are
rarely due to aneurysm. The most common causes of damage to the fourth nerve
in this region are trauma and ischemic vasculopathy. The most likely result
from damage within subarachnoid space is an isolated fourth nerve palsy.
Due to the large number of other neural structures that
accompany the fourth nerve as it travels through the cavernous sinus and
superior orbital fissure, it is unlikely that the patient will exhibit an
isolated fourth nerve palsy due to damage within these areas. More likely,
there will be an associated palsy of cranial nerves III and VI. Common
causes of damage to the fourth nerve in these areas are herpes zoster,
inflammation of the cavernous sinus or posterior orbit, meningioma,
metastatic disease, pituitary adenoma, and carotid cavernous fistula. Trauma
to the head or orbit can cause damage to the trochlea, resulting in superior
oblique muscle dysfunction.
A CN4 palsy often presents suddenly, but may
additionally result from decompensation of a longstanding palsy. In order to differentiate these two types of palsies, examine old photographs of the patient. A patient with a decompensated longstanding palsy will present with
a compensatory head tilt in old photos. Further, patients with decompensated longstanding fourth nerve palsies will have an exaggerated vertical fusional ability. Longstanding CN4 palsies typically are benign and no further management is necessary.
In the case of complicated CN4 palsies, (i.e.,
those that present with other concurrent neurological dysfunction), the patient should undergo neuroradiological studies dictated by the accompanying signs and symptoms. In the case of isolated CN4 palsies caused by recent trauma, the patient should undergo an MRI or CT scan of the head to dismiss the possibility of a concurrent subarachnoid
hemorrhage. If the CN4 palsy is not associated with recent trauma, investigate for a history of past trauma. If the CN4 palsy is due to previous trauma and has recently decompensated, you can manage the diplopia with vertical prisms.
If the patient is elderly and has a CN4 palsy of
recent origin, perform ischemic vascular evaluation to search for diabetes and hypertension. If the palsy is caused by vascular infarct, it will spontaneously resolve over a period of 3-6 months, periodic observation and
either temporary occlusion or press-on prism therapy.
* Consider cases of true vertical diplopia to be a CN4 palsy until proven otherwise. In children, nearly all cases of isolated CN4 palsy are either congenital or traumatic.
In adults, 40% of all isolated CN4 palsies are traumatic, 30% idiopathic, 20% due to vascular infarct, only 10% due to tumor or aneurysm.
* Majority of CN4 palsies are benign. for sudden-onset isolated CN4 , delay permanent prisms for 3 months to allow autorecovery.
Horner syndrome 1
ptosis (muller muscle weakness in upper lid), miosis, Enophthalmus (pseudo b/o ptosis) and ipsilateral anhydrosis of the face (if external carotid invo.
Other findings:
- Iris blue or heterochronmia if lesion happened before age 2
- Loss of ciliospinal reflex (pinching back of neck C2-C3 afferent cause pupillary dilation)
- Raeder para-trigeminal syndrome= orbital or periorbital pain, miosis and ptosis is considered varient of migraine, if associated with CN 3to6 palsy is due to middle cranial fossa mass
There is a 3-neuron pathway to the 3 end organs (Muller muscle, External carotid branches, Iris dilator) involved.
1sr order sympathetic fibers arise from the hypothalamus, descend uncrossed through the mid brain and pons, and terminate in the intermediolateral cell column of the spinal cord in the C8-T2 segments.
2nd order preganglionic fibers exit the spinal cord at the level of T1, enter the cervical sympathetic chain, ascend and synapse in the superior cervical ganglion at the level of the bifurcation of the common carotid artery.
Postganglionic fibers then travel along the ICA. Sudomotor fibers branch off, and travel along the ECA to innervate the blood vessels and sweat glands of the face.
The pupillomotor fibers enter the cavernous sinus, then enter the orbit through the superior orbital fissure along with the ophthalmic branch of the trigeminal nerve (Vi) via the long ciliary nerves. Then, the long ciliary nerves innervate the iris dilator and Muller muscle (which elevates the eyelid along with the levator palpebrae - a cranial nerve Ill innervated muscle).
Horner syndrome 2
- idiopathic most common
- congenital, hereditary (auto dom) usually associated with iris heterochromia/albinism (blue eyes) as iris pigmentation is under sympathic control before age 2
- central lesions in hypothalamus, medulla wallenberg, upper cervical cord syrongomyelia, demyelination, trauma
Horner in coma rare but can occur in large cerebral hemorrhage that affected thalamus and hypothalamus. Ipsilateral horner c laryngeal palsy suggest medullary lesion. Horner in SCI means lesion above T2.
- Peripheral causes Pancoast tumor, trauma, carotid artery dissection or trauma or TB Sarcoidosis in upper cervical lymph nodes. Horner c cranial neuropathy of 9-12 can be associated c carotid artery blow out a fatal complication of lateral laryngeal space infection.
Horner syndrome 3
Dx and DDX
Determination of Horners synd and localization of the defect in the sympathetic system can be achieved c cocaine (2-4%) and hydroxyamphetamine (1%) eye drops: cocaine inhibits the re-uptake of norepinephrine.
Dx of Horner:
Cocaine instilled in an eye c intact sympathetic innervation will produce dilation of the pupil. A sympathetically denervated pupil dilates poorly to cocaine, regardless of the level of the sympathetic system lesion.
Read eye dilation 30 min after Cocaine drop
DDx of preganglionic vs postganglionic lesions
Hydroxyamphetamine stimulates the release of NE from presynaptic postgang nerve terminals. Hydroxyamphetamine instilled into an eye with Homer synd with intact postgang fibers (i.e., first- or second-order neuron lesions) dilates the pupil. An eye c damaged postganglionic fibers (3rd-order neuron lesions) doesnt dilate.
24 h wait between 2 drops
1 or 2 can not differentiated from each other.
- Chest CT or CXR
- MRI and MRA or CTA
- Document lesion is old or long standing,check old photos or driver license, if one eye is blue lesion happened before age 2
- DDx with Adies or Argyll Robertson eyes, Miotic drugs or Senile miosis or physiologic anisocoria
The vestibulo-ocular reflex is mediated by the semicircular canals. Optokinetic nystagmus requires foveal fixation and smooth pursuit. Both have saccadic eye movements as a component.
Neuroophthalmology No Value Extraocular muscle movement
Rule out: MG; Myopathy
Eye movement
ocular bubing in icu pt bad prognosis
in thalamic lesions
in pvegstate pt can have pursuit occipital movement saccadic eye movement in frontal eye feild
optokinetic nystagmus with strip drum they should have downward saccad in PSP they loose it
Opsuclonus myoclonus of eye
The triad of optic ataxia, ocular apraxia, and simultanagnosia (Balint's syndrome) is usually the result of bilateral occipitoparietal junction lesions.
The combination of dysconjugate, highly variable nystagmus, head nodding and head tilt without ophthalmologic abnormalities, and with normal neuroimaging, is diagnostic of spasmus nutans. Latent nystagmus is a jerk nystagmus that is evoked or enhanced by covering one eye. Congenital nystagmus is usually conjugate and suppressed by convergence (in contrast to spasmus nutans, that is typically increased by convergence). Opsoclonus describes chaotic, conjugate saccades, seen classically in the paraneoplastic syndrome associated with neuroblastoma. Whipple's disease produces a convergence-divergence nystagmus with associated movements of the muscles of the head and neck (oculomasticatory myorhythmia).
Prosopagnosia (in which visual perception is intact but there is an impaired ability to recognize the identity of the perceived figure by vision alone) is nearly always associated with bilateral lesions involving the occipitotemporal junctional area.
The optic nerve provides inputs to the superior colliculus (for reflex saccades), lateral geniculate nucleus (relay of the visual pathway), pretectal nucleus (relay of the light reflex) and the suprachiasmatic nucleus (the circadian pacemaker). The medial preoptic nuclei would be spared by enucleation of the eye.
The pupils react normally in Horner's syndrome, while lesions of the parasympathetic pathway are associated with poor or absent reaction of the pupil to light.
Vertigo d/t ear disease
1) BPPV: secs in duration, positional, no ear symptoms, 25%trauma, 25%URI, paroxysmal, 50%balance problems, Dix-Hallpike: geotropic (nystagmus to down affected SC canal), latency, then crescendo decrescendo, then habituation, audio NL, tx: Epley (CRM).
2) Meniere's: hours in duration, not positional,+HL/tinnitus, sensation of ear fullness or pain, rare precipitating factors, recurrent, NL balance, DH: acute, Audio: low freq HL, tx: low salt/caffeine, diuretics, vasodilation, surgery (non destructive v. destructive: intratympanic gentamycin, labyrinthectomy, vestibular n. resection).
3) Vestibular Neuronitis: days in duration, not positional, occ. mild HL/tinnitus, post URI, not recurrent,+balance problems, DH: early nystagmus, audio: nl,tx: vest. rehab.
NeuroOtology Smell Smell Dysosmia
parosmia triggered by another odor or phantosmia spontaneous

-trauma head and nasal
- sinusitis
- toxin chemiacal exposure meds
- post viral URT infections
- idiopathic
stop new med or possible med
cbc cmp b12 tsh ana esr spep zinc
mri of brain and base of skull
CT 5 mm cut through ethmoid, cribriform plate, temporal bone
Saline nasal drops 10 cc in each nostril in head down position tid or qid
GBP up to 900 mg/day or Zonergan 200 mg/day
Amitriptyline 50-150 qhs
NeuroOtology Taste Taste Dysgeusia
-meds in last 3 months discontinue may takes 3 m to heal eg lunesta, cardizem, topamax, ct, antirheumatologic etc
-poor oral dental hygiene
- impair saliva production
- hypothyroidism
- low B12 or Zinc
- viral men/encephalitis, herpes
- Lupus Sjogren etc
- idiopathic
stop new med or possible med
cbc cmp b12 tsh ana esr spep zinc
mri of brain and base of skull
CT 5 mm cut through ethmoid, cribriform plate, temporal bone
food prepration: chew slowly, add spice, marinate, use orange lemon, add small amount of MSG, serve hot amd steamy
zinc gluconate 40 mg tid no matter def or nor zinc has 2 fx taste cell generation improve salivary fx
Cepacol lozenges with benzocain prn
Xylocaine mouth gel 0.5 to 1 percent bid or tid
GBP up to 900 mg/day or Zonergan 200 mg/day
Amitriptyline 50-150 qhs
Burning mouth disorder
after dental tx
nasal sinus infection
fungal infection of mouth tongue
abx therapy
vit B or Iron def.
Kidney disease
BP meds eg ACE Inhib
klonopin 0.5 to 2 mg/d
GBP 1200/d
Baclofen 30 - 60 mg/d
Lamictal 200/day
or combination of above
- Alz type II in hyperamonia, no cytoplasm like nonreactive astrocyte
- Creutzfeldt in demyelinating
- Bergmann in cerebellar ischemia
- atypical bizzare astro in PML
- Chaslin in subpial gliosis normal
Down synd
box brain for frontal lobe shape
cortical thining
arhinoencephaly- abcense of olfactory nerve and bulb
Agenesis of CC
can be associated c Aicardi (retinal calcification, coboloma, sz), dandy walker, tourette synd, chromosomal abn eg triosomy(dysmorphic face)
associated c prox bundle
Hippocampus purkinje cells begin to die after 4 min of total anoxia and ischemia, total brain limit of viability 10 minute.
Intracytoplasmic inclusions in oligodendroglia, termed glial cytoplasmic inclusions (GCIs), are found in multiple system atrophy (MSA). GCIs are immunopositive for alpha-synuclein and MSA is considered by some to be a "synucleinopathy." Neuronal intranuclear inclusions are found in Huntington's disease and other CAG-polyglutamine expansion diseases. Intranuclear "ground glass" inclusions in oligodendrocytes are characteristic of progressive multifocal leukoencephalopathy (JC virus infection). The characteristic inclusion body seen in rabies encephalitis is the Negri body, which is found in the cytoplasm of large neurons.
-Cowdry A solitary large in herpes family, PML, SSPE
-Cowdry B in Polio acute multiple small inclusions
results from failure of early neuronal migration or later postmigrational cortical destrucion.
Seen in
- IU hypoxia or hypoperfusion
- peroxisomal disorders eg Zellweger, neonatal adrenoleukodystrophy
- Fukuyama congenital muscular dystrophy
thickening of cortex
smooth brain actual defect is pachgyria. associated with genetic defect LIS1 and REELIN gene defect.

The cell shown contains a neurofibrillary tangle -an intraneuronal intracytoplasmic inclusion composed of paired helical filaments. The section has been stained with a silver stain. Neurofibrillary tangles can be seen in a variety of conditions including Alzheimer disease, Pick disease, progressive supranuclear palsy, Down syndrome, Parkinson-dementia complex of Guam, and post-encephalitic Parkinsonism.
Triplet diseases
Myotonic dystrophy
Fragile X
Friedrich ataxia
SCA spinocerebellar ataxia
Neuropathology Brain tumors Angioinvasive branching fungal hyphae are characteristic of aspergillosis and mucormycisis. In contrast, in blastomycosis, coccidioidomycosis, cryptococcosis, and histoplasmosis rounded yeast forms are seen. Candidiosis has both fprm hyphae and yeast.
The photograph shows a biphasic cellular population consisting of small reactive lymphocytes and large neoplastic germ cells, which is characteristic of germinoma -the most common pineal region tumor. Pineocytomas, in contrast, are composed of small mature pineocytes that form large rosettes with fibrillary cores. Pineoblastomas are densely cellular primitive neuroectodermal tumors that often form Homer Wright (neuroblastoma-type) rosettes and occasionally fluerettes. Pineal astrocytomas show prominent eosinophilic cytoplasmic processes. Regarding terminology, the designation "pinealoma" is an inaccurate, arcane and imprecise historical relic that should not be used; it dates to a time before a distinction was made between germinoma and pineoblastoma.
St Anne/Mayo classification of astrocytoma
grade I none
II pleomorphism
III pleomorphism + mitotic figure
IV + neovascularization or necrosis
Neuropathology Infection 4 forms of CNS TB- basilar meningitis, tuberculoma, abcsess, malacia or paranchymal form
AIDS CNS- d/t HIV, Opportunistic infections, Neoplasm
The astrocyte illustrated in the photomicrograph is a Creutzfeldt astrocyte. These reactive astrocytes are characterized by multiple small nuclei (micronuclei) and abundant eosinophilic cytoplasm. Although not pathognomonic, they are typically seen in demyelinating diseases and serve as a red flag to alert the pathologist to consider demyelinating disorders in the differential diagnosis. There are a number of other types of astrocytes with distinctive morphology. The Bergmann astrocytes of the cerebellar cortex send long cytoplasmic processes from the Purkinje cell layer to the pial surface and show striking proliferation in response to ischemic insult. Alzheimer type II astrocytes can be seen in many types of liver failure that result in hyperammonemia. They differ from all other reactive astrocytes in lacking discernible cytoplasm; rather, the nuclei are enlarged, pale, with only a thin marginal rim of chromatin, and are often irregular in shape. Superficial reactive astrocytosis occurring in the normally very hypocellular molecular layer is referred to as Chaslin’s subpial gliosis. Finally, highly atypical, bizarre reactive astrocytes can be seen in progressive multifocal leukoencephalopathy (caused by infection with the JC virus).
Cocaine, like amphetamine, binds to the presynaptic dopamine transporter (DAT) inhibiting dopamine reuptake and increasing dopamine concentrations in the nucleus accumbens. This mechanism underlies the acute reinforcing effects of these drugs of addiction.
The hypocretin/orexin system of the lateral hypothalamus has been implicated in the mechanisms of narcolepsy. These neurons project to cholinergic and monoaminergic cell groups involved in regulation of REM sleep. Reduced CSF levels of hypocretin and reduced numbers of hypocretin cells have been found in patients with narcolepsy.
NMS d/t insufficient stimulation of dopamine receptor participated by neuroleptics tx c bromocriptine.
Statin myopathy d/t inhibition of mevalonic acid synthesis, precursor of several essential metabolites including Coenzyme Q10 (ubiquinone)
This toxic action potentiate by clofibrate, gemfibrozil, nicotinic acid, cyclosporine.
Fish/Shellfish poisoning
Saxitoxin in NE NW USA
Ciguatoxin in FL HA
brevotoxin in gulf of Mexico & Caribbean
Domic acid (glutamic agonist)in eastern Canada
Tetro dotoxin in Japan by puffer fish
neurologic ADR
Bactrim chemical meningitis
Vancomycin ototoxic
Ethambutol optic neuropathy
Zalcitabine for HIV sensory neuropathy
Acyclovir tremor
CT Agents
methotrexate intrathecal transverse myelopathy
Cisplatin sensory polyneuropathy
5FU cerebellar dysfunction
Vincristine peripheral neuropathy/Sz
BCNU necrotizing encephalopathy
Neurotransmitter metabolism
After presynaptic reuptake, neurotransmitters are metabolized by specific enzymes. Some of the metabolites can be measured in the cerebrospinal fluid as an indirect index of activity of the corresponding neurons. GABA is metabolized by GABA-transaminase to succinic semialdehyde, which serves as a precursor in the Krebs cycle. Monoamines are metabolized by monoamine-oxidases and methyltransferases. The final metabolite of dopamine is homovainillic acid; of norepinephrine is 3-methoxy-4-hydroxy-phenylglycol (MHPG), of serotonin 5hydroxyindoleacetic acid (5-HIAA), and off histamine methyl-imidazolacetic acid (MIAA)
po takes 1 hour
im,sc 30 min
iv 6-15 min takes to reach Cmax or kick in
It needs about 3-5 half life to reach steady state.
PO narcotis usually half 4-5 halflife, parenteral 3 hours.
for normal takes one day to adjust the dose, for XR c halflife of 8-12 h dose adjustment should be 2-4 d, for methadone dose adjustment qweek.
not recommended
Demerol noremeperidine longer hl than demerol and they get build up.
Propoxyphene or Darvocet useless
Dependence vs Addiction
if dose reduction required reduce by 25-50% q 3-4 days.
How to cope c beureau of narcotics:
- notify in writing about practice change
- document phy-pt relationship
- chart every prescription
- schedule III drug tylenol3, lortab can be called in and you may be cheated
Ptosis (upper lid reach or cover pupils)
-mitochondrial myopathy
-in old ages ocilopharyngeal muscular dystrophy
- myotonic dystrophy stiner disease
- MG (in ALS no ptosis ladt muscle to get involved)
papapa/bababa tatata/lalala kakaka/gagaga respectively show lip tongue palate weakness
AC nuc meissner, pedunculopontine
NE LC labeled by tyrosine hydroxylase
GABA CerebellumGPi SNpars reticulata label GADecarboxylase
Glutamic acid subthalamic nuclei label by glutaminase
Glycine Spinal cord
Histamine hypothalamus tuberomamillary nucleus
Glutamic activation of NMDA receptor requires presence of glycine
Vitamin deficiencies
Pyridoxine deficiency results from dietary deficiency of pyridoxine, and has occurred in infants given formulas in which the sterilization process has destroyed pyridoxine, or in milk from unusual sources that is intrinsically deficient in pyridoxine (such as goat's milk). It should be distinguished from pyridoxine dependency, an autosomal recessive disorder in which mutations producing conformational changes in glutamic acid decarboxylase cause early onset seizures that are controlled by pharmacologic doses of pyridoxine.Cobalamin (vitamin B12) deficiency may follow inadequate dietary intake (as in some vegetarian diets), or malabsorption with or without intrinsic factor deficiency. Patients typically have a slowly evolving syndrome of loss of posterior column function, with parethesias, loss of vibration, proprioception and two point discrimination, and eventually spasticity and cognitive impairment.Thiamine deficiency most often occurs because of inadequate diet, as in alcoholics. Individuals with marginal diets may develop overt symptoms of thiamine deficiency if their remaining reserves are depleted by glucose loading. Acute thiamine deficiency causes Wernicke's encephalopathy, characterized by ataxia, confusion and abnormalities of eye movements.
Neurophysiology Evoked Potentials VEP
- Check size to be 30-40 formaximal visual stimulation
- Make sure pt look at the center of the screen
- Indications
MS, Pseudotumor, Optic nerve trauma, Postsurgical cahnges, Neoplasm
- Acoustic neuroma interpeak latency I-V
- Cochlea patholgy
- MS pattern good I and II but IV and V distorted because MS is intraparanchymal pathology in brain stem
- BAEP not sensitive to drug but sensitive to hypothermia
- Interoperative monitoring
- Hearing loss in infants and neonates
- Spinal cord pathology Transverse Myelitis
- MS
- Intraoperative monitoring
Motor EP or
acute infarct has dec ADC in contrast to T2 shine through
if lesion truly an acute infarct it should remain bright on adc map
MS lesion have high ADC
BG changes
- GP CO poisoning
- Putamen methanol
Putamen, Thalamus Wilson
- Leighs disease
- BG cacification Fahr's disease
- BG iron deposit Hallverdon Spatz
pnk gene panthokinase def
- Caudate trophy Huntington
- Caudate hypertrophy Sydenham chorea
- Kernicterus unconjugated bilirubin passes into selected nuclei, especially globus pallidus, subthalamus and Ammon's horn in term infants.
late onset neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome. In the globus pallidus can be observed the “eye-of-the-tiger” sign, described originally in this disorder and later found also in cortico-basal-ganglionic degeneration and in progressive supranuclear palsy.
Depressed fx
compound when skin laceration
penetrating when dura is torn
Epidural more arterial lens shaped and more with lucid interval c/t SDH.
if fresh SDH maybe isodense and be missed on CT.
fMRI, PWI, MRSpectroscopy
Perfusion-weighted MR imaging (PWI) allows an assessment of perfusion of the brain microvasculature. PWI requires intravenous gadolinium contrast that causes a paramagnetic susceptibility effect. MRI signal declines as gadolinium transits the microvasculature. One of the uses of PWI is to complement the information obtained by diffusion-weighted MRI (DWI) in acute stroke patients. A variety of perfusion properties of the contrast bolus can be calculated, such as cerebral blood volume, cerebral blood flow, mean transit time, time-to-peak, and time of arrival. Flow-related enhancement is used in MR angiography. Changes in venous oxygenation are used in functional MRI. Magnetization transfer pulses, such as those used in MR angiography, measure magnetization transfer effects. MR spectroscopy measures brain metabolites such as choline in parts per million (ppm).
Normal brain myelination is a dynamic process that begins during fetal life and continues after birth in a predictable manner. The progress of the myelination is seen as changes in white matter signal on the MRI image. In the term infant, myelination is best assessed on the T1-weighted image where it is seen as high signal. Normal adult patterns are seen by 18 months of age. Some areas, such as the white matter dorsal and superior to the ventricular trigone, have persistent high signal on T2-weighted images, which should be considered normal. These association fibers often become myelinated by the second or third decade of life.
In proton magnetic resonance spectroscopy, the N-acetyl aspartate peak is an index of neuronal integrity; lactate acid of anaerobic glycolysis, phosphocreatine of energy metabolism, and choline of membrane synthesis and degradation.
Inc signal in T1 -
hemorrhage, fat, melanoma(melanin, pr rich tissues), contrast, mucin, ca(hydrated)
keratin hypodense in T1
Hyperintensity on T1-weighted image results from shortening of T1 relaxation time. This is seen in a variety of tissues on noncontrast images, most commonly, blood, fat, calcium, and protein-rich tissue.
Toxic leukoencephalopathy is associated with exposure to therapeutic agents (particularly antineoplastic drugs), drugs of abuse and environmental toxins. Hyperintensity of white matter on T-2 weighted sequences is characteristic, and the diagnosis should not be made in the absence of such changes. Methotrexate and carmustine are the anticancer drugs most commonly implicated in toxic leukoencephalopathy. Carbon monoxide poisoning typically produces demyelination that begins days to weeks after exposure. Alcoholism produces a number of changes, including an excessive number of white matter hyperintensities, loss of total white matter volume and preferential involvement of the frontal white matter that correlates with observed neuropsychological deficits.
Elongated lesion demonstrating hyperintensity on T2 -weighted images is most consistent with multiple sclerosis (MS) and represents focal demyelination. Degenerative myelomalacia may have these signal characteristics and ill-defined margins, but there is no adjacent spurring or other degenerative bony disease to have caused this problem. Ependymoma would be seen as a more focal mass with cord enlargement. Syrinx has well defined cavity margins, though would be of similar signal intensity as the lesion pictured. The lesion is too dorsal for motor neuron disease. MS cord lesions are usually one to two segments in length, or less.
Both images demonstrate the missing vermis thus the 4th ventricle connects with the cisterna magna, the hallmark of Dandy-Walker malformation. The posterior fossa is enlarged.
Ring enhancing lesion
cysticercosis cyst
resolving hematoma
less likely mass
Schmorl node
Vertical disk herniation
may cause LBP esp in teenagers active in sport activities.
May not be detected in plain x ray films
If it cause inflammatory response in bone marrow eg low intensity on T1 and high intensity on T2 around the node need to be treated or will be symptomatic.
Common in mid and lower spine, common in teenagers, may cause radicular pain if there is signal changes in MRI
Causes- trauma young athlets, (rare causes hyperpara, osteoporesis, osteomalacia, infection, tumor)
Tx- NSAIDs, rest, prevention of axial pressure on spine
White matter changes
- leukodystrophies
MLD ant sparing u fiber
ALD occi parietal sparing u fiber
Canavan diffuse involves u fiber
Krabbes associated with brain atrophy
- gliomatosis cerebri
- post leukoencephalopathy in htn mtx toxicity, eclampsia
- Binswanger's disease in HTN, pseudobulbar affect
- CADASIL blood genetic test
- Cocaine Heroine abuse
- B 12 def myeloencephalopathy
- glue or spray sniffing as a form of recreational drug use. Toluene exposure over time causes cognitive deficits and white matter abnormalities in cerebral white matter.
Toluene toxicity is often the result of "recreational" abuse by sniffing and inhaling fumes from spray paint cans. Patients who chronically inhale toluene vapors develop dementia (clinically consistent with subcortical dementia), cerebellar ataxia and long tract findings, and in some cases cranial nerve palsies. It is not uncommon for these patients to also manifest a paranoid psychosis. MRI demonstrates a diffuse leukoencephalopathy, cerebral atrophy, and T2 hypointense lesions of the thalamus and/or the basal ganglia.
front alexander MLD
post adrenoleukodystrophy
sparing u fiber
multifocal adem
Vanishing white matter disease
No Value eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee Steroid Equivalency
Cortisone 25 qd eg hydrocortisone
Cortisol 20
Prednisone 5
Prednisolone 4 eg methylpredniso
Dexamethasone 0.5 mg

Ped Neurology
Pemoline and methylphenidate have both been of some benefit in the treatment of attention deficit disorder in children. Clonidine, a central agonist of the alpha-2 adrenoreceptors, is helpful to decrease hyperactivity and impulsivity in these patients.
ADHD and obsessive-compulsive symptoms are often associated with Tourette's syndrome. Boys are more often affected than girls. An increase in seizures is not seen. Coprolalia is not necessary for the diagnosis.
Tic can be seen in ADHD, OCD
Tourette can get worse by psychostimulant such as methylphenidate. Tx c haloperidol, pimozide, clonidine
Ped Neurology
Board oral exam
- localization
- diff
- dx
- management
- family counseling
3 yo c NV weakness intact reflexes, salivation-
GBS, MF, organophosphate poison, porphyria, infections, rabies, rhomboencephalitis listeria unpasteurized milk, amebia negleria swimming in water, tick bite, bickerstaff encephalitis,
tx ABx, IVIG,
Ped Neurology
Chromosomal disorder
Down trisomy 21
Turner XO
Prader-Willi & Angelman syndromes
DNA Deletion in ch 15q (all PWS pt inherit a deleted ch 15 from father, all AS pt inherit defective ch 15 from mother)
PWS defective hypothalamus-dec GH short stature, hypogonadism, hyperphagia obesity, thermoinstability.
AS pt happy puppets c flat head, jerky movement, protruding tongue, bouts of laughter
Ped Neurology
Dandy Walker
- agenesis of cerebellar vermis
- cystic dilation of post fossa
- hydrocephalus
could be associated c
- CCAgenesis
- AS aqueductal stenosis
- Heterotopia
compression of post fossa lead to
- apneic spell
- nystagmus
- truncal stenosis
- CN palsies
- hyperreflexia
Ped Neurology
Developmental delay
progressive vs static (CP)
progressive- WM vs GM
GM- sz, cognitive deficits, personality changes, blindness
WM- corticospinal tract, FND, hyperreflexia, ataxia, gait difficulty
- infections
- metabolic
- toxins
- child abuse
- ALTE, acute life threatening event
- vascular, stroke
- lysosome storage disease progressive
- fatty acid oxidation when they get sick or starved they try to metabolize FA and it goes to faulty metabolism and cause neurological deficits.
tx at acute stages is giving pt high glucose. Don't let them fast.
screening for long chain, medium chain FA
serum Aminoacids
Urine organic acids
the clue is get the test when they get sick, hand them list of the tests need to be done when they come to ER.
self mutilation- Lecsh Nyhan, any hereditory sensory autonomic neuropathy, amyloidosis, Fabry
LN purine metabolism, high uric acid, chorea

BG bil-
methanol, co, mercury, organic aciduria, Farr's disease deposit of iron ca, wilson, hyparthyroidism, HIencephalopathy, mitochondrial disease, leukodystrophy

Stepwise worsening of pt in response to infections/fever
- mithochondrial disorders
- AA, OAciduria eg glutaric aciduria
- Leukodystrophy
- FA oxidation metabolic disorders
serum VLCFA perioxisomal disorders, Carnithin profile level for deficiency that can also be seen with VPA tx (give carnithin 400 mg tid or 1-3 g/day)
- Urea cycle disorders
- lysosome storage disease eg gaucher
- toxic antipschotis phenothisins
- tetanus
- BG disorders mithochondrial, Hallovorden Spatz, Wilson
- Gaucher
- Sandhoff
- OAciduria
- malignant hyperthermia
Ped Neurology
Glycogen storage diseases
Pompe's disease is a lysosomal glycogen storage disease that affects practically all tissues and
results from a defect of 1,4-glucosidase (acid maltase). Hypotonia, failure to thrive, and decreased reflexes develop during the first few months of life. Cardiomegaly is prominent in infantile forms, which more commonly present with pulmonary insufficiency. Unlike other glycogeneses, the liver is normal in size or only slightly enlarged and there are no abnormalities of glucose homeostasis. PAS-positive glycogen is seen in membrane-bound vacuoles in muscle, hepatocytes, and Schwann cells, but no abnormalities are seen in myelin sheaths.
Ped Neurology
Infantile botulism usually presents between 3 and 18 weeks of age. The disease is caused by the C. botulinum toxin which blocks acetylcholine release. Clinical features include constipation, hypotonia, areflexia, poor suck, impaired pupillary response to light and ophthalmoplegia. The infants are often breast-fed. Diagnosis is made by EMG with repetitive nerve stimulation, causing an incremental response and isolation of C. botulinum toxin in the stool.
Children who develop infantile botulism typically are normal at birth and develop normally until the second to fifth month of life. Hypotonia then develops, accompanied by constipation. On examination the patient is quite weak and areflexic. Compound muscle action potential recording in response to 50 Hertz stimulation produces a diagnostic incrementing response.
Ped Neurology
Menke disease
primary defect in intestinal transport of copper. dec copper and ceruloplasmin in serum
kinky hair eyebrow, cheek fullness micrognathia, high arch plate, sz (myoclonic), lethargy hypotonicity,
w/u radiography of long bone for ostegenesis imperfecta, hair analysis, genetic test for ch Xq13 mutation
Tx- copper supplementation c copper histinate
Ped Neurology
Metabolic & Storage diseases
- GM1 Gangliosidoses ß Galactosidase
- GM2 Gangliosidoses Hexosaminidase
- Fabry disease á Galactosidase
- Gucher ß Glucosidase
- Nieman Pick Sphingomyelinase
- Faber disease Acid ceramidase
- Wolman disease Acid lipase
- Refsum disease Phytanic acid ãhydroxylase
- Cerebrotendinous xanthomatosis
- Neuronal lipofuscinoses (Batten) CLN1-5 gene products
- Metachromatic Leukodystrophy
- Krabbe Leukodystrophy
- Hurler synd
- Hunter synd
- Sanfilippo synd
- Morquio synd
- Maroteaux-Lamy synd
- Sialidoses
- Salla disease
- Fucosidosis
- Mucolipidosis II III IV
Peroxismal disease
- Zellweger (cerebrohepatorenal synd)
- Adrenoleukodystrophy
- Refsum disease
Cherry-red spot
- Tay Sachs
- Sialidosis usually
- 50% of Niemann Pick
- 50% of GM1 Gangliosidosis
- Farber disease(inconstant)
- Metachromatic leukodystrophy
Conjunctival telangiectasia
- Ataxia telangiectasia
- Fabry disease (glycolipids accumulation in cerebral blood vessle stroke, glomeruli, PN pain c autonomic manifestation, typical rash in lower half of body)
Ped Neurology
Migraine in children
- no gender difference
- quicker onset
- shorter duration
- variants
benign paroxysmal vertigo
paroxysmal torticollis
cyclic vomiting
hemiplegic/basilar migraine
confusional migraine
Ped Neurology
Neurocutaneous ds
causing sz in infancy
- Incontinentia Pigmenti
- Linear Nevus Sebaceous Synd.
- Neurofibromatosis (I c optic glioma II c acoustic schwanoma)
- SWeber synd
- TScelrosis c SEGA

Tumors associated with
Neurocutaneous ds
- Neurofibromatosis (I c optic glioma II c acoustic schwanoma) most tumors esp neurofibroma/schwanomas
- TScelrosis c SEGA
- von Hippel Lindau c cerebellar hemangioblastoma
- bathing trunk nevus c skin or CNS Melanoma
Ped Neurology
Neurodegenerative disorder
WM- loss of motor skills, spasticity, ataxia
GM- loss of intellectual skills (dementia), Sz, blindness
Ped Neurology
Newborn child with Apnea
Meabolic disorders
Ped Neurology
Non epileptic spells in pediatrics
divide to c LOC and s LOC
1) Syncope
- Pallide infantile syncope frightened or cold blow to face
- Cyanotic infantile spasm, older, temper tendrum, breath holding spells
2) Cardiac dysrhythmia (prolonged QT syndrome)
3) Migraine (basilar artery migraine) ophthalmoplegic, hemiplegic, vertigo, NV not much HA, ca channel mutation, ATPase mutation
4) Psychogenic mutation
6) GERD, first 1-2 months with apnea, syncope, sandifer syndrome (arching)
7) HVT with dizziness, syncope
8) Sleep disorders
-Parasomnias: night terros(+FHx), Somnambulism, Somniloquoy
-Sleep myoclonus
- Narcolepsy/Cataplexy
- OSA (big tonsils)
Movement disorders in general eg chorea, Tics, GERD (sandifer), shrudding attack (shaking attack), Paroxysmal kinosiogenic dyskinesia, Hyperekplexia (Jumping frenchman of Maine, New Orleans, Quebec, Stimulus myoclonus from Glycine receptor gene)
Most Sz inPeds are cryptogenic (perhaps more genetic related)
<3 months infants have RAM onset sleep especially after feeding.
Almost all neonatal sz are partial <3-6months.
Ped Neurology
Normal milestones
Ped Neurology
Rett syndrome
DDx- autism, CP, nonspecific developmental delay
normal up to 6-18 months then regression with problem with expressive language, loss of purposefull hand movement, stereotype hand movement washing, wringing, tapping, clapping, unsteady gait, stiff leg/toe walking
May have Sz, bruxism
Mutation in MECP2 gene on X chromosome
Tx- sowing of motor disability, PT/OT, and or elbow splint for reducing hand movement, intermittent weighted mobilization, music and hydrotherapy, speech therapy for communication skills, scoliosis management by ortho, prevention of bone loss ca, agitation tx less stimulating environment, laxatives for constipation
Ped Neurology
Storage diseases
Seizures, blindness, psychomotor retardation are cardinal features of Tay-Sachs disease. Tay-Sachs disease is an autosomal recessive disorder in which hexosaminidase A is deficient and hexosaminidase B is increased. The disorder is panethnic, but is more frequent in Ashkenazy Jews. Prenatal diagnosis is now available. Hepatosplenomegaly is not a feature of Tay-Sachs disease, but does occur in Sandhoff disease (deficiency of hexosaminidase A and B). Macrocephaly is frequent in GM2 gangliosidoses.
Zellweger's cerebro-hepato-renal syndrome presents with hypotonia and cranio-facial dysmorphic features and the brain shows widespread neuronal migration defects, especially pachygyria and cerebellar abnormalities. Wolman's disease, due to acid lipase deficiency, presents with diarrhea, vomiting, failure to thrive, hepatosplenomegaly and adrenal calcification, but minimal CNS abnormalities. Farber's disease is characterized by painful swelling of the joints and subcutaneous nodules; neurons show stored material but widespread migrational abnormalities are rarely found in the brain. Pompe's disease is primarily a disorder of muscle and presents with hypotonia, and while neurons and astrocytes may show increased storage of glycogen, there are no associated migrational disorders in the brain. Krabbe's leukodystrophy demonstrates no migrational disorders in the brain.
Fabry's disease is an X-linked defect in the alpha-galactosidase. It is characterized by painful peripheral neuropathy with autonomic manifestations, a typical rash in the lower half of the body, and accumulation of glycolipids in the endothelium of cerebral vessels and glomerular arterioles.
Current therapy for Bassen-Kornzweig disease includes high dose vitamin E; for Hartnup disease, nicotinic acid; for Refsum's disease, dietary restriction of phytanic acid; and for multiple carboxylase deficiency, biotin.
Ped Neurology
Sturge-Weber disease
is characterized by a meningeal vascular malformation and calcification in the second and third layers of the underlying cortex.
can be associated c port wine nevus on the face
maybe progressive
do ophthalmology consult for glucoma
may have HA cause NV
sz control c pb
check MRI q6m or annual hemiatrophy
skull x ray for ram track
SWeber clinic
check for hemiparesis
pb syrup alcohol based some kids don't like it can use tab 30 mg half bid
take c only little water or formula
Von Hippel Lindau
hemangioblastoma in cerebellum
renal cell carcinoma, pheochromocytoma
parynchymal cyst PCKidney liver
Osler Weber Randau
hemorrhagic Telangectasia leptomeningial
GI hemorrhage
Ped Neurology
Tegretol 100 chewable tablets
no generic substituation
100 bid for 5 days
100 tid for 5 days
continue Dilantin 5 mg/kg/day orally for 2 weeks then taper to dc over 2 weeks
check cbc cmp teg level in 3-4 weeks at pcp office
- baseline lfts if not done
- neuro f/u in 2 months
Ped Neurology Ataxia Ataxia DDx
Acute recurrent ataxia
1- Drug tox (psychoactive drugs, AEDs, antihistamines esp in setting of OM)
2- brain stem encephalitis or post infectious eg ADEM, Miller Fisher, MS, Myoclonic encephalopathy and neuroblastoma
3- Genetic
Episodic ataxia like PParalysis
Hartnup, Maple, Pyruvate DH def.
4- Migraine basilar or BPVertigo
5- Epilepsy pseudoataxia
6- Trauma hematoma postconcussion
VB dissection
7- Vascular cerebellar stroke hemo, Kawasaki disease
8- Conversion
9- Hydrocephalus magnetic gait
Chronic static or progressive ataxia
1- Congenital malformation
cerebellar degeneration, AC or DW malformations, basilar impression (odontoid pressure on spinal cord)
2- Brain tumor eg cerebellar astrocytoma, hemangioblastoma VHL disease, ependymoma, medulloblastoma
3- Herditary
SCA spinocerebellar ataxia triplet disease
Metabolic hartnup, maple syrup, GM2 gangliosidosis, pyruvate def, ramsy hunt synd, refsum (HSMN IV, deafness)
Most common Friedreich ataxia
Ataxia Telangectasia (recurrent sinopulmonary infection, oculomotor apraxia, ataxia telan(malar, conjunctival which develop before nystagmus & ataxia),choreoathetoid movement, inc risk of B cell neoplasia eg lymphoma, Hodgkin or ALL)
X Linked
ADLDystrophy(white matter, spasticity, behavioral changes ddx in adult c adrenalmyelinoneuropathy)
Leber optic atrophy
The syndrome of spinocerebellar degeneration is most characteristic of prolonged chronic vitamin E deficiency.
hereditory ataxia
Friedrich ataxia
Adult ataxia-SCA
Machado Joseph disease
DentoRubropallidoal atropy
Ataxia Telenctgasia
Ped Neurology Ataxia Friedreich Ataxia
Lesions associated with Friedreich ataxia include degeneration of the posterior columns, corticospinal tracts, spinocerebellar tracts and dorsal roots. Anterior motor neurons are not affected.
ataxia more truncal than appendicular, dec position vibration in LEs, ddx with severe combined degeneration of B12.
triplet GAA Frataxin Ch. 9 mithochondrial inner membrane iron deposit
- spinocerebellar degeneration panel
CAG triplet repeat, ataxia panel
- EKG ECHO more cardiomyopathic hypertrophy than dysrrhytmia c dyspnea on exertion chest pain(the more triplet repeat more cardiac involvement, Ibedonide)
- NCS/EMG more dec amp in sensory normal motor
- SPEP Vit E (def)
- GTT 10% develop DM
- Ortho consult for scoliosis >35%
- MRI of brain for cerebellar degeneration, AC or DW malformations, cerebellar astrocytoma, hemangioblastoma, ependymoma, medulloblastoma
- MRI of spine for cord atrophy
- Tx vit E, coenzyme Q, mithochondrial cocktail carnitine, NIH Study drug name for prevention of hypertrophic cardiomyopathy.
The syndrome of spinocerebellar degeneration is most characteristic of prolonged chronic vitamin E deficiency.
5 hydroxytryptophan new treatment for FA
Ped Neurology Hypertonicity Hypertonicity
respiratory distress
tonic sz dt birth asphyxia, meningoencephalitis or metabolic abnormality
- check for metabolic problems lactic pyruvic acid, aminoacids organic acid
- ammonia level
neonatal drug withdrawal
neonatal tetanus
sandifer gerd
neuromuscular pathology
Ped Neurology Hypotonicity Hypotonicity1
- ammonia level
- check for metabolic problems lactic pyruvic acid, aminoacids organic acid, CPK
- TSH, FT4
- Chromosomal study
Dysgenetic syndromes eg Down
Prader-Willi synd, Zellweger, Riley-Day (familial dysautonomia) synd.
toxins eg fetal exposure to heroin, dilantin, etoh or tridione can also cause dysmorphism and hypotonia
Perinatal insults to brain spinal cord eg birth asphyxia, hypoxic/ischemic brain injury, ich, bacterial/viral infections, metabolic disturbances, extereme prematurity
- spinal cord injury following iu malpositioning or traumatic birth
(sphincter dysfx and loss of sensation below midchest)
NM disorders-
- SMA Most common a recessice disorder Werdnig-Hoffman-limb weakness areflexia tongue fasciculation
- Poliomyelitis
- Infantile neuropathies
eg metachromatic leukodystrophy, adrenaloleukodystrophy, giant axonal neuropathy, petoneal muscular atrophy
- infectious diphteria, GBS, tick paralysis, infantile butulism
- Myasthenia congenital nonimmunologic vs neonatal
- Myopathies congenital (central core, nemaline, myotubular), metabolic(Pompe, mitochondrial, cytochrome-C oxidase def.), myotonic dystrophy
Connectiv tissue disorders-
congenital ligament laxity, Ehlers-Danlos, Marfan
- congenital hypoglycemia/hypothyroidism (have hypothermia)
- aminoaciduria, organic acidemia, ca disorders, renal tubular acidosis, metabolic cerebral degenerations (leukodystrophies, lipid storage diseases, peroxisomal diseases,
mucopolysaccharidosis , aminoacidurias, Leigh synd.)
Focal neonatal hypotonia
flaccid arm imply brachial plexus injury BPI upper bpi maybe with ipsilateral diaphragm paralysis, loer bpi with ipsilateral Horner
dx by emg, spinal evoked potential or mri may show nerve root avulsion
Leg hypotonia/weakness-
spinal dysraphism, caudal regression synd., arthrogrypotic leg seformity or gross maldevelopment of the leg associated c sacralagenesis (seen in 15% of dm mothers)
Ped Neurology Hypotonicity Hypotonicity2
frog leg position
head drop more then 45
if central they have dec MS, hyperreflexia
Central causes of hypotonicity
HIE [multiorgan failure and encephalopathy/sz/low APGAR score alone is not enough, not 1-5 min but 10 minute APGAR is relevent] /Trauma,
metabolic aquired eg T4 vs inborn errors AA OAciduria

brain malformation,
chromosomal abn (21, cri du chat, pradder willi)
Ant horn cells- SMA 123, Autosomal recessive 25% chance in other kids, dec movements in uterine, dx by DNA test blood cells or skin fibroblast, life expectency less than 6-18 months,
need feeding tube, res failure intubation like locked in syndrome.

Congenital polyneuropathy
congenital myasthenia about 6
transient mother MG
Congenital myopathies most prominent present at birth is myotonic dystrophy and congenital myopathies eg nemaline ..., mitochondrial
Ped Neurology Mitochondrial disorders Mitochondrial disorders
- Leber optic atrophy
- Leigh dz
- MELAS (mitochondrial tRNA leu, MRI shows post cerebrum j farct and almost always BG hypodensity and calcification)
Kearns-Sayre synd or congenital progressive ext opgthalmoplegia
- mitochondrial DNA analysis
- skin fibroblast for cytochrome c oxidase

MELAS -mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes is one of several mitochondrial encephalopathies. In cases where a clear maternal inheritance has been established, there is a mutation in the mitochondrial tRNA leu. Cranial CT and MR scans in patients with MELAs reveal infarct-like areas bilaterally in the posterior cerebrum and almost always hypodensities or calcifications in the basal ganglia region.
- for myoclonus klonopin or lamictal
- mitochondrial cocktail:
co enz q10 30 mg qd
nicotinamide 500 mg bid
riboflavin 500 mg bid
vit c 1000 mg qd
succinate 25 mg qd
- avoiding condition that incbody energy demand (fasting, overexertion, infection/fever, hot temp)
- avoiding meds that inhibit respiratory chain eg DPH, Barbiturates
- avoid meds that inhibit mitochondrial pr synthesis eg tetracycline, chloramphenicol
Ped Neurology Stroke Stroke in neonate
-if high cpk check for mithochondrial disease if continue to be high muscle biopsy
mitochondrial genetic tests
- check for metabolic problem LA, PA, AA and OA acids
- apolipoprotein
-apl abs, lupus anticoagulant
- ana, esr, rpr
- homocysteine
- check for coagulation abn
- hypercoagulabe test for venus sinus thrombosis stroke and hemorhagic transformation
- underlying tumor
- vascular malformations, AVM
- head trauma
Lobar hemorrhage:
Hemorrhagic mets-renal,melanoma,choriocarcinoma,
A study of 160 children from 36 weeks gestation to 18 years of age with radiographic confirmation of cerebral sinovenous thrombosis found that 58 percent of children had seizures, 76 percent had diffuse neurologic signs, and 42 percent had focal neurologic signs. 43 percent of patients were neonates, and 54 percent were under one year of age. Risk factors were present in 98 percent of cases, and included acute systemic illness, head and neck disorders and abnormal tests for prothrombotic disorders (in 38 percent). Seizures at presentation and the presence of venous infarcts predicted adverse neurologic outcomes.
DeVeber G, Andrew M, Adams C, et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001;345:417-423.
in low birth weight premature <1500 Dx by US indicated in neonate <32 week of gestational age should be repeates by 2 weeks of age and garding based on maximum hemorrhage seen
I hemorrhage in germinal matrix only
II IVH s ventriculomegaly
III IVH c ventriculomegaly (30-40% chance of motor/cognitive deficit)
IV IVH c ventriculomegaly c periventricular hemorrhage (60-80% chance of motor/cognitive deficit)
there is also risk of hydrocephalus in IVH. pt should have frequent f/u c pediatrician
Tx- maintaine acid-base balance, avoid fluctuation in BP, indomethacin for prevention of severe hemorrhage 0.1 mg/kg/dose IV Q24 hr x three doses, initiated at 6-12 hr of age.
Ped Neurology Stroke Strokes in kids
- MoyaMoya
- Kawazaki (IgE fluctuation, conjunctivitis, rash, erythema, edema)
- Venus infract, d/t NVD
cerebral AD areteriopathy c subcortical infarct and leukoencephalopathy
Notch 3 gene on ch 19, media is replaced c eosin PAS positive congo red neg material, systemic vasculopathy, dx by skin nerve biopsy.
Ped Neurology Sz DDx of sz in <2yo
*Apnea >15 sec or if c bradicardia lesser
2 type- cyanotic(breath holding spell )vs pallid syncope
cyanotic provoked by anger,fear, frustration pallid by pain like bump on head
both brainstem release phenomenon
flat EEG then get normal,
in cyanotic anger, fear -crying-cyanosis-apnea-loc
in pallid pain-white pale-limp-loc
tx- piracetam 40mg/kg/day or keppra effective in 92%
picking up the child will prolong spell, hold the child c head in dependent position
also get ECG to r/o prolonged QT synd.
other DDx
* dystonia
transient paroxysmal dystonia of infancy
glutaric aciduria
* migraine
benign paroxysmal vertigo
paroxysmal torticollis
cyclic vomiting, confusional state
* steretypies finger tapping, hair curling
*sandifer GERD
* Sz
febrile(complex if focal, >15 min, + FHx, + FND), nonfebrile, myoclonic
Neurocutaneous ds causing sz in infancy
- Incontinentia Pigmenti
- Linear Nevus Sebaceous Synd.
- Neurofibromatosis (I c optic glioma II c acoustic schwanoma)
- SWeber synd
- TScelrosis
DDX of sz in >2
- hyperventilation synd.
- narcolepsy-cataplexy
sleep paralysis (generalized hypotonia on awakening), hypna gogic hallucinations (vivid visual auditory hallucination on awakening)
- night terrors
- startle disease
- paroxysmal dyskinesia
kinesigenic vs nonkinesigenic
choreathetoid sec to min
dystonic min to hours
- syncope
- migraine
- sz
Ped Neurology Sz Infantile Spasm
onset after 2 m peak 4-6 m
etio- one third cryptogenic, 2/3 b/o CNS malformation (lisencephaly, holoproencephaly, double cortex, abscence of CC), acquired brain injury, TS, IEM (organic, aminoaciduria), chromosomal abn 13,17,18
poor px
TX- ACTH(gel 20-40 U/24 hr IM QD x 6 weeks or 150 U /m2/24 hr : BID for 2 weeks then gradual taper)(pt should be in hospital for at least 2 days check bp q8h, guaic stool, parents learn to give injection), VPA, Clonazepam (0.5 mg bid to tid), LAM, TOP(30mg bid up to 9 mg/kg/day), Zonisemide, ketogenic diet(pt in the hospital for 2days starvation then use high fat no sugar diet watch for hypoglycemia many loose too much weight loss), surgery
SE of TX such as risk of infection, lyte abn, htn, gi hemorrhage dw parents
Ped Neurology Sz Neonatal sz
tonic, myoclonic, clonic or subtle (blink, chew, bicycling, apnea) b/o immature CNS.
etio- HIE 35-42%, ICH 15-20%, CNS infection 12-17%, CNS malformations 5%, metabolic (dec glu, ca, B6, toxins)3-5%, IEM 5-20%
1) search for acute causes-glu, ca, na, mg, suds, sepsis w/u (LP, CT, EEG)
2) IF abov

Sz wu
-if febrile pancx, lp c herpes pcr
-mri c sz protocol
- check for metabolic problem lactic pyruvic acid, aminoacids organic acid
- ammonia level high level in favor of urea cycle disorder need HD as well as scavenger tx c Na pheylacetic and Na benzoate also send sample to Pittsburgh for AA OAcids
- post traumatic or postsurgical
pb 15 mg/kg loading dose 5 mg/kg maintenance dose start after 12hours check level before that
use dilantin
keppra m dose 45mg/kg
topomax 12.5 mg bid
vpa sprinkle
Jitteriness in neonates
metabolic disorder
addicted mother
perinatal asphyxsia (multiorgan failure, 5 min apgar less than 3) any
episode of hypoxia sufficiently severe to cause brain damage also causes derangements in other organs. mild HIE irregular HR, pass meconium. Severe HIE lactic acidosis, inc LFTs, entrocolitis, RF, MI
DDx of neonatal sz by peak time of onset
24 hours
infections- sepsis, meningitis, IU
IVH at term, SAH, HI encephalopathy
Laceration of tentorium or falx
Direct drug effect, B6 def
24-72 hours
all of the above plus hypocalcemia (Ca<7 mg/dl d/t low birth weight, asphyxia, maternal DM, transient neonatal hypoPTH, maternal hyperPTH, DiGeorge syndrome,
after 72 hours in maternal hyperPTH, DiGeorge syndrome as well as feeding by cow milk or improper formula)dec PTH, AA OA met disorder, Urea cycle disorder, TS Incontinentia pigmenti
72 hours-1 week
all of the above
familial neonatal sz
cerebral dysgenesis
1 week-4 week
all of the above
herpes encephalitis
Drug withdrawal- marijuana, etoh do not cause drug dependence in the fetus, ot happens c heroin, methadone, codeine, propoxyphene
Ped Neurology Sz Neonatal sz
tonic, myoclonic, clonic or subtle (blink, chew, bicycling, apnea) b/o immature CNS.
etio- HIE 35-42%, ICH 15-20%, CNS infection 12-17%, CNS malformations 5%, metabolic (dec glu, ca, B6, toxins)3-5%, IEM 5-20%
1) search for acute causes-glu, ca, na, mg, suds, sepsis w/u (LP, CT, EEG)
2) IF above normal, evidence of encephalopathy or IEM or recurrent sz then
plasma AA, CSF AA,CSF Imino acids, CSF Pyruvate
urine OA, urine sulfites
serum PA, LA, ammonia, PH, very long chain FA (VLCFA), Neurotransmitters

Infantile Spasm
onset after 2 m peak 4-6 m
etio- one third cryptogenic, 2/3 b/o CNS malformation, acquired brain injury, TS, IEM
poor px
TX- ACTH(gel 20-40 U/24 hr IM QD x 6 weeks or 150 U /m2/24 hr : BID for 2 weeks then gradual taper)(pt should be in hospital for at least 2 days check bp q8h, guaic stool, parents learn to give injection), VPA, Clonazepam (0.5 mg bid to tid), LAM, TOP(30mg bid up to 9 mg/kg/day), Zonisemide, ketogenic diet, surgery
The cerebrospinal fluid in preterm newborn infants without bacterial meningitis and without other disease can have a protein of 65-150 mg/dl and the white blood cell count can have a range of 0-29 cells/cu mm with a mean of nine.
2- Headache
most common form tension HA
No association c hormonal changes
80% of migrainour imrove 15% some, 5% get worse
- Pre/E ususally after 20 w
- Pseudotumor
- Sagital ST usually after 16-18 w get MRV
- inc in pituitary adenoma size
- AVM become symptomatic
hypoglycemia, dehydration can make HA worse
MRI indications
first worst HA of life, thunder clap HA, FND, systemic dz, meningismus
CT c abdominal sheild
for mild tylenol, tylenol3, percocet, vicodin (apap+hydrocodon)
for severe HA, amitrip /doxepin questionable C cat 10 mg qhs safest, nortrip, zoloft, prozac
Caffeine can be used <300mg/d
Mg oxide 400 to 800 mg/day
B2 200mg bid
behavioral therapy, moist heat, ice packs
- ASA, NSAIDs B in 1, D in 2-3 trimester
- Opiates eg MS, Demerol 50-100 mf iv prn
- antiemetics promethazine, dimenhydrinate, meclizine, compazine, reglan C, phenerga
- Mg 1 g IV over 30 min
- Triptans contraindicated, only if other tx fails, registry, Ergot x
A cocktail-
IV Compazine+ IV Narcotics+ IV dexamethsone
for acute attack- demerol 50-100 mg po max dose 1-1.8 mg/kg up to 150 mg
PO/SC/IM/IV q3-4h
for menstrual migraine/sz can get OCP, Acetazolomode 250 mg bid
preventive- Inderal, metoprolol xl (lowest effective dose, cat C in 1-2, D in 3 trimester), Calan

Cyproheptadine B 2mg bid for 3 days then 4 mg bid for 3 days then 4 mg tid until 2-3 weeks before pregnancy as it may cause neonatal hypoglycemia,
Elavil questionable,
Short course steroid Prednisone better than dexameth which crosses the placenta more readily
4- Stroke
steroid 2 3 rd trimester ok
IVIG postpartum
interferone not in pregnancy and breast feeding
ms and oc
no contrdiction
if positive ana and apl should not use oc

Obstetric Neurology and Pregnancy
Preexisting disease
- Epilepsy
- Migraine/HA
- MS
- MG
- Movement didorders, Parkinson, RLS
- Stroke
- ALS/MN Diseases
Pregnancy complications
- Stroke/CVA
- Neuropathy
Postpartum angiopathy
part of hypertensive angiopathy, causing (sever thunderclap) HA, SZ, FND, visual deficits
associated c HTN, Pregnancy, eclampsia, migraine, vasoactive drugs, uremia, methtroxate
two imaging pattern- PLS post leukoencephalopathy associated with small vessele disease endothelial dysfx and breakdown of BBB, vasogenic edema, loss of autoregulation
RCV reversible cerebral vasoconstriction involving medium large arteries with segemental narrowing
- r/o vasculitis, ESR, ANA, RPR, SUDS
- r/o sinus thrombosis by MRV
- Can check for Fibrin split products etc, peripheral blood smear
- tx of HTN
- MRA, CT Angio, 4V Angio, TCDoppler
- Usually resolves in 10-20 days
Pseudotumor cerebri idiopathic intracranial HTN
worsen during pregnancy but healthy baby
usually develop after 14 w disappear after 1-3 months, obese or gain weight during pregnancy
- check VF, VA, BSpot
- if CSF>35 is severe
- moderation indiet to prevent weight gain
- if vision loss prednisone or dexa x 2 weeks
- 4-6 LP can be done sometimes weekly before considering optic nerve fenestration or lumboperitoneal shunt
- Acetazolomide 250 mg qd or bid start and inc by 250 mg qw to max 500 bid , should start after20w gestation
- Lortab or Tylenol3
- pain control during delivery to dec acute rise in CSF pressure
- pt c pseudotumor frequently have migraine but can diff it, that's my pressure HA, the other my episodic migraine HA
Pregnancy 1- Eiplepsy
Fetal vitamin K deficiency with hemorrhagic complications occurs in 10% of neonates born from mothers receiving antiepileptic drugs that induce liver metabolism of vitamin K, including phenobarbital and phenytoin. Women taking enzyme-inducing antiepileptic drugs should be treated with vitamin K1, 10-20 mg daily PO during the last month of pregnancy. Infants should receive 1 mg intramuscularly at birth and, if needed, fresh frozen plasma.
Foldvary N. Treatment issues for women with epilepsy. Neurol Clin 2001;19:409-425.
Safest AEDs all of them have risk esp VPA for neural tube defect, need to be on 1-4 mg FA daily at least 3 months before pregnancy
less risky Lamictal, CBZ
- Cataminial sz d/t inc est few days before start of bleeding or drop in progest few days after start of bleeding
true dx need pt record 6 months hx of sz and menses
tx- extra dose of AED during vulnerable period, progestrone use Provera, acetazolamide for 10 days
AEDs withdrawal should be contemplated 6 months before planned pregnancy.
For neural tube defect- check afeto pr at 14 and 16 week, level 2 ultrasound at 20 week, if any abnormality check amniosynthesis fluid for a feto pt and ACholine estrase.
WWEpilepsy have more
- anovulatory cycle
- hypogonadotropic hypogomadism
- hyperprolactinoma
folic acid 4mg a day
aeds level decreased during pregnancy esp lamictal by more than 65 percent
check level q month

Pregnancy 3- Neuropathy
- most of them involve femoral n. at inguinal ligament
- L5L4 lumbosacral trunk plexopathy at pelvic brim when cushion effect of psoas muscle finish it is compressed by baby head in women c short stature, big baby, prolonged or arrested labor, forceps use
SS- w of ankle dorsifle ion toe dorsiflex as well as eversion inversion
no w in plantar flexion S1 or ankle reflex was normal
EMG/NCS- no block over fibular head,no paraspinal involvement x rarely b/o epidural anesthesia, dec proneal CMAP, dec MUAP L5
predominant path demyelination traction injury usually resolve in 3-4 months if axonal may takes up to one year
DDx of radiculopathy root vs plexus
- paraspinal involved in root
- sensory CNAP or SNAP involved in plexopathy (lesion distal or at dorsal root ganglia)
femoral vs L3-L4 radiculopathy (also involves obturator neuropathy=thigh adduction w medial thigh n) happens in pelvic injur/sur lithotomy or retropritoneal hematoma or pelvic mass c hip flex
knee ext weakness, loss of knee reflex and ant thigh numbness
sciatic neuropathy (post tibialis + common proneal) ddx stroke in foot area of motor cortex, radicuolopathy
causes-muscular or bony pressure on sciatic, post hip dislocation, acetabular fx,im injection
all foot ankle w plus knee flex w plus
loss of achilles reflex and foot lateral leg n
proneal palsy- ddx c L5 radiculopathy(also involves foot inversion w as it carries out by post tibialis) ss foot drop, foot dorsiflexion eversion w no inversion weakness, lat leg n
causes: stretch injury by forcible
foot inversion, compression by tight stocking cast crossed leg or trauma
Meralgia paresthetica- lat femoral cut nerve- lat thigh n no ref or
motor w
causes- obesity, pregnancy, weight loss, or heavy equipment belt wihch cause compression of nerve under femoral ligament
ddx c L2 L3 radicucause motor w or
knee areflexia
Morton metatarsalgia- tight shoes compress toes nerves esp 3 and 4 one causing patchy paresthesia
Atypical antipsychotic
- Zyprexa 2.5 mg qhs, neutral
- Seroquel less EPS, sedative
- Geodon activating
side effects of antipsychotics
EPS,acute dystonia, akathisia (acute), tardive dyskinesia (chronic rabbit synd.), inc Prolactin, weight gain, hyperlipidemia, obesity
- olanzapine Zyprexa is drug of choice
- fast acting tolerated better than Haldol
- can be given IM or oral disintegrating tablet or mixed c water juice or nancarbonated beverage for fast acting

- clozapine most effective least EPS, agranulocytosis
- olanzapine weight gain DM hyperlipidemia
- quetiapine OH Catarct, least EPS, worst weight gain
- respiridone fast acting depot form available
- Geodone prolonged QT, penultimate best in no weight gain
- Abilify some dopamin agonist, best no weight gain, lowest agranulocytosis
Chronic fatigue syndrome
Approach to pt with persistent fatigue:
- record the medical and psychosocial circumstances at onset of symptoms
- Assess previous physical and pschological health
- Seek clues to an underlying medical disorder (eg fever, weight loss, dyspnea)
- Assess the impact of the symp on the pt life style
Characteristic symptoms of chronic fatigue synd include fatigue, myalgia, arthralgia, impaired memory and concentration and unrefreshing sleep
check for hypothyroidism, chronic hepatitis, chronic anemia, Neuromuscular disease, sleep apnea syndrome, occult malignancy
PE in CFS is normal
Mental examination
- Past or family history of psychiatric disorder, notably depression, anxiety
- Past hx of frequent episodes of medically uneplained symptoms
- Past hx of alcohol or substance abuse
- Current symptoms: depression, anxiety, self destructive thoughts, and use of OTC meds
- Current signs of psychomotor retardation
- Evaluate psychosocial support system
CFS pts have depressive symptoms but not guilt sucidal ideation or observable psychomotor slowing
Labs investigations
CBC, CMP, ESR, ANA, RPR, Hepatitis profile, Ca PO4
Random blood glucose and Thyroid function tests
1- unexplained persistent or relapsing chronic fatigue lasting 6 or more consecutive months that is of new or definite onset; is not the result of ongoing exertion; in not substantially relieved by rest; and results in substantial reduction in previous levels of occupational educational social or personal activities; and
2- Four more of the following symptoms occuring concurrently: 10 impairment of shortterm memory or concentration 20 sore throat 30 tender cervical or axillary LNs 40 muscle pain or multijoint pain 50 HA 6) unrefreshing sleep and 7) postexertional malaise

TX see comprehensive physhiatry kaplan saddock
Conversion exam
MS- loss of childhood memory
low monotone speech, poor historian and not contributing to hx and exam
CN- unable to see but respond to visual threat or do visual fixation or follow you in the room
- split of vibration over forehead
- cornea nasal reflex
SENSORY- c/o sensory problems but higher cortical sensory intact
REFLEX- no reflex changes or atrophy
MOTOR- give away weakness
- + Hoover sign
- the whole limb moves en bloc no distal drop
- contraction in hamstring when you hold leg up like if to push it down
speech-rapid, circumstantiality
thought-flight of ideas
mania in child can be confused with ADHD.
Mania in adults can be associated with substance abuse.

FDA approved drugs- Li, VPA, Olanzepine
Tegretol also very good
mental status exam
inverse pyramid (no lobe approach)
executive fx
visuospatial orientation
- arousal
- basic attention eg digital span normal is 7- + 2
around 5
- concentration eg spelling word backward, months of the year
- answering questions appropriately
- aphasia, paraphasia, anomia
- registration, recent working memory test by 3 words, remote (has no localization stored all over places)
- 3d cube
- copy pentagon
- dividing line to 2 equal part
- mimicking hands like you
executive functions
- drawing clock 10 after 11, 3 step commands
- judgememt
- calculation
Panic Attack
(even in pregnancy)
- Paxil CR 25 mg qd
- trazodone 50-100 mg qhs
- Avoid Xanax cat D
- Check for TSH FT4 MVP EKG
Depression due to medical condition Lexapro 5 mg qd can increase to 10 mg qd after few days lowest sideeffects
Depression during pregnancy
Trazodone C 50-100 mg qhs
DDx manic-depression c borderline personality
shortest manic episode is 4-7 days personality is few hours
Anxiety during pregnancy
Buspar Category B
Bipolar treatment
Lamictal also has good antidepressant effect
Atypial Antipsychotic
In refractory case of Li or VPA treatment, can add lamictal or atypical antipsychitic
Antidepressant is not recommended in tx of bipol ar because they increase mania phase of their illness
Aggression behavior/psychosis
Haldol 5 mg + 1-2 mg Ativan or 50 mg Benadryl
outpt Olanzapine 2.5-10 mg/day
- clozapine most effective least EPS, agranulocytosis
- olanzapine weight gain DM hyperlipidemia
- quetiapine OH Catarct, least EPS
> 1 month
reminiscences of stress
persistant inc arousal state such as exaggerated startle response
The pathophysiology of schizophrenia as associated with pathological changes in the dorsomedial thalamus and the dorsolateral prefrontal cortex thereby affecting the pathway between the two sites. Any role of pedunculopontine, nigrostriatal, hippocampal-fornical-mamillary, and amygdala-orbitofrontal pathways is not clearly established in schizophrenia if in fact there is a role in these pathways.
Brains at autopsy taken from schizophrenic patients show an increase, not decrease, in ventricular size, especially of the temporal horns of the ventricles due to loss of cortical gray matter in medial temporal lobes.
Both auditory and visual hallucinations, persecutory delusions, and ideas of reference are seen in both temporal lobe epilepsy (TLE) and schizophrenia. A positive family history of schizophrenia, schizoid personality, or schizotypal personality is often present in schizophrenia but usually not in TLE. Affect is better preserved in TLE than in schizophrenia.
ADHD and obsessive-compulsive symptoms are often associated with Tourette's syndrome. Boys are more often affected than girls. An increase in seizures is not seen. Coprolalia is not necessary for the diagnosis.
dissociative state- fugues, psychogenic amnesia, hypnosis. material is available in the preconscious but selectively ignored.
Sleep disorders
Excessive daytime sleepiness
- Insufficient sleep
- PLMD periodic limb movement dis.
- Stimulant withdrawal
- Sedatives
- Circadian rhythm disorders
- Psychiatric disorders
- Malingering
- Idiopathic
Drugs for tx of EDS
Dextroamphetamine 5-60 mg
Methamphetamine 5-60 mg
Methylphenidate 10-60 mg
Mazindol 0.5-6 mg
Modafinil 100-400 mg
Pemoline 20-115 mg

Drugs for tx of cataplexy
Protriptyline 5-60 mg
Imipramine 10-100 mg
Desipramine 25-100 mg
Clomipramine 10-150 mg
Fluoxetine 20-60 mg
Venlafaxine 75-225 mg
Reboxetine 2-10 mg
Sodium oxybate 4.5-9 gram

Sleep disorders
Sleep 1
NREM and REM sleep alternate, with each cycle lasting for approximately 90-100 minutes. Four to six such cycles are noted during a normal sleep period. the first one third of a normal sleep episode is dominated by slow-wave sleep (SWS) and the last third is dominated by REM sleep.
The first REM sleep episode is noted 60-90 minutes after the onset of sleep. REM sleep accounts for 20-25% of sleep time.
Arousal is a shift in EEG frequency shifts lasting for 3-14 seconds and includes alpha, beta, or theta activities but not spindles or delta waves. The subject must be asleep for 10 consecutive seconds before an arousal can be scored. In REM sleep arousals are scored only when accompanied by a concurrent increase in submental electromyographic (EMG) amplitude. Unless accompanied by EEG frequency shifts, K complexes, delta waves, artifacts, and increased submental EMG activities are not counted as arousals. An arousal index is defined as the number of arousals per hour of sleep and up to 10 can be considered as a normal arousal index. The usual arousals signifying sleep fragmentation.
The newborn infant spends approximately 50% of the time in REM sleep, but by 6 years of age this time is decreased to the normal adult pattern of 25%. On falling asleep, a newborn baby goes immediately into REM sleep or active sleep, which is accompanied by restless movements of the arms, legs, and facial muscles. In premature babies, it is often difficult to differentiate REM sleep from wakefulness. By 3 months of age, the NREM-REM cyclic pattern of adult sleep is established. However, the REM-NREM cycle duration is shorter in infants, lasting for approximately 45-50 minutes and increasing to 60-70 minutes by 5-10 years, and the normal adult cyclic pattern of 90-100 minutes by the age of 10 years. Sleep spindles begin to appear at approximately 3 months and K complexes are seen by approximately 6 months of age.
Sleep disorders
Sleep 2
A characteristic feature of sleep in old age is marked attenuation of the amplitude of delta waves and, therefore, during scoring of delta sleep, which depends not only on the rate but also on the amplitude of delta waves, the percentage of delta waves decreases. The other characteristic feature during old age is the repeated awakenings throughout the night, including early morning awakenings. Depending on the sleep habit, two groups of individuals are recognized: evening types (Owels) and morning types (Larks). Morning and evening types are most likely determined by genetic factors.
An average adult's sleep requirement is approximately 7.5-8.0 hours, regardless of environmental or cultural differences.
Kripke and co-workers found that chances of death from coronary arterial disease, cancer, or stroke are greater for those who sleep less than 4 hours or more than 10 hours compared with those who sleep an average of 7.5-8.0 hours.
Approximately 80% of dreams occur during REM sleep and 20% occur during NREM sleep. REM sleep dreams appear to be more highly emotionally charged, complex, and bizarre, whereas NREM dreams are characterized by more realistic and rational facts. The significance of dreams remains unknown. Some suggestions include activation of the neural networks in the brain, restructuring and reinterpretation of data stored in memory, and removal of the unnecessary and useless information from the brain during dreams.
Sleep-promoting neurons are thought to reside in the preoptic area of the anterior hypothalamus and wake-promoting neurons in the posterior area. Sleep results from both passive and active processes.
The active hypnogenic neurons for NREM sleep are located primarily in the preoptic area of the anterior hypothalamus and the basal forebrain area as well as in the neurons in the regions of the nucleus tractus solitarius in the medulla.
Sleep disorders
Sleep 3
The sleep-promoting role of the anterior hypothalamus depends on inhibition of the posterior hypothalamic histaminergic awakening neurons.
The pons is, therefore, sufficient and necessary to generate all the signs of REM sleep.
Neurons in the pedunculopontine tegmental (PPT) and the laterodorsal tegmental (LDT) nuclei in the pontomesencephalic region are cholinergic and are the REM-on cells, which are responsible for REM sleep, showing increased firing rates at this stage. The REM-off cells are located in the locus ceruleus and raphe nucleus; these cells are aminergic neurons and are inactive during REM sleep. Histaminergic neurons can also be considered REM-off cells. A reciprocal interaction between the cholinergic REM-on and aminergic REM-off neurons in the brainstem is thought to be responsible for REM generation and maintenance.
The systems responsible for arousal include ARAS in the upper brainstem and its projections to the thalamus and posterior hypothalamic regions, the recently described hypocretin (orexin) system in the lateral hypothalamus with its widespread ascending and descending projections (de Lecea et al. 1998; Sakurai et al. 1998), and the system responsible for cognition resides in the cerebral cortex and its subcortical connections.
The term circadian rhythm originated from the Latin circa meaning about and dian meaning a day. Human circadian rhythm generally has a cycle length of about 25 rather than 24 hours (range of 24.7 to 25.2 hours), although this has been challenged recently.
The human body also has an internal biological clock. The paired suprachiasmatic nuclei (SCN) of the hypothalamus above the optic chiasma are the sites of the biological clock. The master circadian clock in the SCN receives photic information from the retinohypothalamic tract, which sends signals to multiple synaptic pathways in other parts of the hypothalamus, the superior cervical ganglion, and the pineal gland where melatonin is released. The SC
Sleep disorders
Sleep 4
The SCN contain melatonin receptors and there is a feedback loop from the pineal gland to the SCN.
Melatonin is secreted maximally during the night and is an important modulator of human circadian rhythm for entrainment by the light-dark cycle. The melatonin level rises fairly abruptly in the evening and then reaches its maximum level between 3:00 am and 5:00 am after which it decreases to low levels during the daytime.
Biological functions of sleep
Body and brain tissue restoration (enhanced synthesis of macromolecules during sleep)
Energy conservation
Memory reinforcement and consolidation (take place during REM)
Synaptic neuronal network integrity (REM sleep maintains motor circuits, whereas NREM sleep maintains nonmotor activities)
Most of the autonomic changes involve respiration, circulation, thermoregulation, and the pupils (e.g., pupilloconstriction during sleep). During NREM sleep, there is an overall tonic increase in parasympathetic activity, which increases further during tonic REM sleep. In addition, during phasic REM sleep, sympathetic activity decreases. Sympathetic activity during REM sleep, however, increases intermittently, which results in swings of blood pressure and heart rhythm, causing bradytachyarrhythmias.
Sleep disorders
The hypocretin/orexin system of the lateral hypothalamus has been implicated in the mechanisms of narcolepsy. These neurons project to cholinergic and monoaminergic cell groups involved in regulation of REM sleep. Reduced CSF levels of hypocretin and reduced numbers of hypocretin cells have been found in patients with narcolepsy.
Somn ambulism in stage 3-4 of NREM sleep
PNT, hypotonia and PGO spikes in REM sleep
Spinal cord
Ant Syndrome
Clinical features:
Sensory loss:
Pain & temperature
Weakness: Legs ± arms
Related lesion:
Ant spinal artery D
Disk; Osteophyte
Spinal cord
Autonomic dysreflexia
major splanchnic sympathetic outflow from T5-L2 is not inhibited by supraspinal centers and any bladder problem, catherterization, bowel retention constipation may cause sweating, tachcardia, hypertension and ...
tx is clonidine and relief of triggering factor.
Spinal cord
Cauda equina Syndrome
Clinical features:
Onset: Progressive; Asymmet
Pain: Severe; Radicular
Fatigue; Fasciculations
Sensory: All modalities;
Lumbar > sacral
Weakness: Lumbar > Sacral
Reflex loss: Knee > Ankle
± Bladder involvement
Related lesion:
Spinal cord
Central Cord
Clinical features:
Sensory loss:
Pain & temperature
Sacral sparing
Weakness: Arms > legs
Related lesion:
Cervical arthritis
Neoplasm: Glial;
Spinal cord
Epidural abcess
back pain with fever
RFs- IVDA, pelvic infection, UTI, Endocarditis, OsteoMyelitis, HIV
Labs- inc CBC, MRI of whole spine
check UA
- Emergency surgical drainage
send surgical swab and tissue for Cx & Sensitivity
- Vancomycin check peak and trough around 3rd dose
- Cardiac echo for endocarditis
- Bone scan with Tc for OM
Spinal cord
(Spastic Paraplegias)
Dominant (Strumpell)
SPG3 (FSP1): Atlastin; 14q
SPG4 (FSP2): Spastin; 2p22
SPG6 (FSP3): 15q11.1
SPG8: 8q23
SPG9: 10q23
SPG10: KIF5A; 12q13
SPG12: 19q13
SPG13: HSPD1; 2q24
SPG17: 11q12
SPG19: 9q33
Multiple exostoses
SPG5A: 8q
SPG5B: ?
SPG7 (5C): Paraplegin; 16q24
SPG11: 15q13
SPG14: 3q27-q28
SPG15: 14q22-q24
SPG20 (Troyer): Spartin; 13q12.3
Sjögren-Larsson: FALDH; 17p11
DRPLA: 12p13
Intermediate # repeats
Spastic paraplegia +:
Dementia &
Extrapyramidal D
Retinal degeneration
Evans syndrome
MLD & Krabbé
SPG1: L1CAM; Xq28
SPG2: Proteolipid protein; Xq21
SPG16: Xq11
AMN: ALDP protein; Xq28
Adult onset: 5q31
Retardation, psychosis, macroorchidism
Spinal cord
(Other syndromes)
+ Arnold-Chiari & Scoliosis
Cleidocranial dysplasia
Acromesomelic dysplasia
Spine Disorders & Myelopathy
Coffin-Lowry Syndrome:
Ribosomal Protein S6 kinase
Morquio's Syndromes:
A: Galactosamine sulfatase
B: b-galactosidase
FGF Receptor-3
Type II Collagenopathies
Spine dysplasias; Spina bifida
Trisomy 21
Ankylosing spondylitis
Lumbar Stenosis
Vitamin D resistant rickets
Other familial syndromes
Arnold-Chiari Malformation
Spastic Ataxias: DRPLA
Hereditary Motor Syndromes
Spastic dystonia syndromes:
DOPA-responsive dystonias:
GTP cyclohydrolase I;
Tyrosine hydroxylase;
Mitochondrial &
Leber's optic atrophy
Infections: HTLV-1
Mass lesion: Meningioma
von Hippel-Lindau
Spinal cord
Fluctuating signs
Slow progression
Partial Brown-Séquard
Epidural abscess: Pain
Parasagittal lesion: Leg
Spine: Disk; Stenosis
Mass: Neoplasm;
Hematoma; Cyst
é spinal root or vessel
Arachnoiditis: Sarcoid;
Mpl surgery; Infection
Toxic: Contrast agents;
Cytosine arabinoside
Multiple sclerosis
ALS: Pure motor
Transverse myelitis:
Vaccine; Immune
Spinal cord
Hemicord (Brown-Séquard) Syndrome
Clinical features:
Ipsilateral loss:
Position sense; Motor
Contralateral loss:
Pain & temperature
Related lesion:
Trauma: Penetrating
Tumor: Dumbbell
Facet; Luschka joint
Spinal cord
Inf (Conus) Syndrome
Clinical features:
Onset: Rapid; Symmetric
Pain: ± Perineum & thighs
Sensory: Saddle; Pain, Temp
Weakness: Sacral
Reflex ê: Ankle > Knee
Bladder D; Impotence
Related lesion:
Spinal cord
usually d/t spinal cord (sensory/motor level, b/b inc, umn in le, lmn at the level of injury, occ respiratory compromise in C4 above)or peripheral nerve (distal weakness or sensory loss, dec ref, atrophy)or brain (CP, ArChMal,MMCell)
1- Trauma (fx, hematoma, concussion, neonatal cervical cord trauma)
2- Cord compression (tumor, abcess, lipoma, TB, Diskitis)
3- Myelitis (devic, ADEM, CVD, lupus,HTLV1, Herpes Zoster, Idiopathic)
4- Tumor(epyndymoma, neuroblastoma, astrocytoma, ewing sarco a)
5- Congenital malformation (arachnoid cyst, avm, atlantoaxial dislocation < in RA, Down, Achondroplasia, Morquio mucopolysaccharidoses<check urine for keratan sulfate>, KlippelFail synd>, ArnoldChiariMal, Myelomeningocele, Tetherd cord syndrome )
6- Familial spastic paralegia AD,AR,XL
7- Metabolic (Adrenomyeloleukodystrophy<inc VLCFA, can be mistaken c MS in young female>, Krabbe<globoid LD, Galactoceramidase def>, Argininemia<Urea cycle disorder, NV, Sz, Para or Quadriplegia>)
Spinal cord
Post Syndrome
Clinical features:
Sensory loss:
Position sense
Relative preservation:
Pain & temperature
Related lesion:
Post spinal artery changes
dec collateral perfusion:
Vitamin def: B12; E
Lipoma; Lig flavum
Spinal cord
ASIA: American Spinal Cord Injury Assoc.
A: complete motor, complete sens
B: complete sens, <3/5 motor
C: complete sens, >3/5 motor

Acute SCI: Methylprednisolone
within 8hrs: 30mg/kg bolus (15min)
<3hrs: 5.4mg/kg/h (45min after
bolus) x 24h
3-8hrs: 5.4mg/kg/h (45min after
bolus) x 48h
- bowel costipation/bladder uti foley care
- decubitus ulcer care
- respiratory care
- autonomic dysreflexia
Spinal cord
Spinal cord synd
- Transverse cord lesion (sensory level d/t tumor, trauma, transverse myelitis, ms)
- Hemicord Brown Sequard
ipsilat weakness, pos vib, contralat pain temp
d/t penetrating injury, ms, lat compression
- Central cord synd cape distribution loss of pain temp intact crude touch c bigger lesion LMN at level UMN weakness below lesion
d/t spinal cord contusion, syringomyelia, tumors (hemangioblastoma, ependymoma, astrocytoma)
- Post cord synd truama, ms, B12 def, tabes dorsalis
- Ant cord synd loss of pain temp, LMN weakness ant horn cell, UMN weakness lat corticospinal tracts
d/t ant spinal rtery infarct, ms, trauma
Cauda equina synd
(neuro emergency)
etio- djd(diskprotrusion, herniation, sequestration, spodylosis), neoplasm, hemo, inf, trauma
ss- bil sciatica,saddle anesthesia, b/b inc, sexual function
in conus more symetrical more saddle anesthesia, in quada more asymetric
L4L5 most common
Tx- neuro emergency
Spinal cord
SPINAL DISORDERS: Points in differential diagnosis
B12 Deficiency
Tumor, Trauma & Toxic
Epidural Abscess & Electricity
Developmental & Hereditary
Spondylosis & Spine
Paraneoplastic & Parasagittal
Multiple Sclerosis & Myelitis
Systemic Disorders
Spinal cord
Motor dec Sensory dec
C3 - Post neck & ear
C4 - Upper neck
C5 Deltoid Shoulder
C6 Pronator Thumb
C7 Ticeps Middle finger
C8 Intrinsic hand 5th finger
L1 Hip flex Groin
L2 Hip flex Ant-Med thigh
L3 Knee ext Cent thigh
L4 Knee ext Med leg
L5 Ankle dorsiflex Large toe
S1 Toe plantarflex Lateral foot
Spinal cord
Spinal Cord lesions
Connective Tissue Disease
Lupus Erythematosis
Mixed Connective Tissue
Systemic Sclerosis (PSS)
Decompression Sickness
Liver disease:
Portosystemic shunt
Aortic Aneurysm
HIV: Posterior columns
HTLV 1: Spastic
Vitamin ê: E; B12
Toxic: Organophosphate
N2O; Heroin
Skeletal lesions
Atlanto (C1)-Axial (C2)
Arthritis: RA; Psoriasis
Trisomy 21
Morquio A & B
Skeletal dysplasias
Klippel-Feil: Cervical
vertebral fusion
von Recklinghausen
Ankylosing spondylitis
Spinal canal stenosis
Coffin Lowry
Stickler dysplasia
Acrodysostosis (lumbar)
Familial Lumbar Stenosis
Vit D resistant rickets
Spondyloarthropathy &
chronic renal failure
Epidural Masses: Gout;
Xanthoma; Large nerves;
Amyloid; Hematopoesis;
Lipomatosis (Steroids)
Spinal cord Transverse myelitis Transverse myelitis
Acute inflammation of spinal cord with dramatic presentation over hours or few days.
- precedingviral ilness or vaccination esp in younger age
- sensory level almost always midthorasic (20 % cervical causing arm weakness); monoapresis or paraparesis; B/B incontinence; back pain in half of them, spinal shock and then UMN signs with babinski later on
- 1/3 mild, 1/3 moderate, 1/3 severe with B/Binc
- Dx requires one of these clinical, CSF or MRI findings
- MRI of spinal cord c GAD urgent at minimum the sensory level and above and ideally total spine to r/o compression b/o disk, mass, epidural abscess
sometime you don't see very much in MRI of spine and detailed repeat study with thin cut through or Somatosensory potentials EP are necessary.
-MRI of brain c GAD to r/o ADEM, MS, and small stroke in corona radiata
- LP and send it for PCR, viral ab (HIV,HTLV1, lyme , herpes family, CMV, WNV etc) and fungal Ag
Also do IgG index, MBP, SPEP on CSF
usually shows mild elevation of Pr or modest lymphocytic pleocytosis
- B12, FA, ESR, ANA, ENA, RPR, HIV, HTLV1, p and cANCA, hepatitis profile
- 25% will progress toward MS like ADEM, usually they have WM changes in brain MRI and need to be started on inf as delayes progression to MS by 1 year
DDx of acute loss of spinal cord function
- Idiopathic autoimmune transverse myelitis as above
- Spinal cordcompression (disk, spondylosis, tumor eg lymphoma, abscess)
- Viral myelitis including HIV
- Spinal cord infarction, AAA, vasculitis
- Spinal cord tumors
- Paraneoplastic myelopathy eg meningitis carcinomatosis
- Syphilis and Lyme
Solumedrol 1gram/day IV for 3-5 days often followed with oral taper
dec inflammation and proteolytic enzymes, stabilize BBB, enhance NCV
- May not offer better prognosis, no trial has been done
- Spinal cord care and team management in severe case
- Put pt on ASA and or Plavix
- Use Neurontin for neuropathic pain or hypesthesia
Cerebral vasculitis
possible causes
- Wegner cANCA (anti proteinase 3)
- PAN, microscopic Polyangitis pANCA (antimyeloperoxidase)
- Hairy cell leukemia blood smear
- d/t Ca check AFP, CEA, PSA, CT C/A/Pelvis
- Intravascular lymphomatosis type of NHL
- APL synd.= arterial/venus thrombosis, abortion, LA or ACardiolipins
- Giant cell arteritis 3% normal ESR, above 40 is significant, check also CRP if high specifity with high ESR is 97%
they can have high APL; LA, AC, ANCA and antithrombin as epiphenomenon as exposure of phopholipis after endothelial damage.
TABx should be done after US exam to make sure TA is not collateral artery to brain. involvement is patch so a fairly long specimen required. immune reaction to elastin. can cause pulseless disease like Takayasu but it is in young women and involve intima autoimmune reaction. in TA only large intracranial arteries get affected.
Drug induced CNS vasculitis- DICV
- Immunosuppression steroids, cyclophosphamide not indicated can be harmful,
- DC Drugs
- Referral to substance abuse clinic
- CaCB like Isradipine may reverse cerebral hypoperfusion
- Lamictal, Gabapentin
APL Syndrome
Sickle cell disease
Cholestrol or cardiac myxoma emboli
radiation vasculopathy
Hepatitis/HIV vasculitis
Fibromuscular dysplasia
- LP, ESR, ANA, Reichlin biopsy, HIV, Hepatitis
- CT 65% sensitive
- MRI, MRA 87% sensitive
- Angio 100% sensitive
Heparin anticoagulation
Mnemonic HEPARIN D
- hypercoagulable states
- embolic stroke carotidogenic/cardiogenic
- pregnancy
- anemia of sickle cell
- recurrent TIA
- increasing TIA
- dissection
The current guidelines recommend treating ischemic stroke patients who present within 3 hours of symptom onset with recombinant tissue plasminogen activator (rt-PA) at a dose of 0.9 mg/kg (maximum dose 90 mg) within 3 hours of symptom onset with 10% of the dose given as bolus followed by infusion lasting 60 minutes. Exclusion criteria include prior intracranial hemorrhage; history of intracranial neoplasm, aneurysm or anteriovenous malformation; stroke or head trauma within the previous three months; gastrointestinal or urinary bleeding within the previous 21 days; major surgery or biopsy of a parenchymal organ within preceding 14 days; recent myocardial infarction; seizure at onset of stroke; history of known heriditary of acquired abnormal hemostasis; current use of oral anticoagulants with prothrobin time>15 seconds, use of heparin in previous 48 hours with prolonged partial thromboplastin time; platelet count <100,000/mm3, and evidence on CT of major hypodensity or sulcal effacement (>1/3 of middle cerebral artery territory), and systolic blood pressure>185 mmHg or diastolic blood pressure >110mmHg, and blood glucose <50 mg/dl or >400 mg/dl.
Vasculitis 1
Primary- small, medium, large artery
- CVD:SLR,Behcet, Sjogren, RA
- Infection: VZV (zoster ophthalmicus), Syphilis, TB, Lyme, infectiveendocarditis, crytococus
- Meds: DPH, Hydralazin
- Tumor: T cell lymphoma
- Serum sickness
Clinical manifestation
- General: encephalopathy, HA
- Focal: multifocal flactuating neurological deficits, myelopathy, sz, sensory neuropathy, sychiatry or sychosis

Anti sm and Anti dsNA
Anti Jo1
-C3 and C4
- Cryoglobulins
- Chronic Hepatitis Panel
- HIV, Lyme
- LP may show inc cell and Pr
- For primary CNS vassculitis MRA and then Angio beading
- CS and bolus MP
- Cyclophosphamide oral and monthly bolus 600 mg/m2 q 4-6 month
- Azathioprine
Vasculitis 2
Large- giant cell, Takayasu, primary CNS vasculitis
Medium c or s Small- PAN, WG,Kawasaki, Chrug Strauss
Small- systemic rheumatic diseases, cancer, microscopic polyarteritis, urticarial vasculitis, Leukocytoclastic vasculitis (Henoch Schonlein purpura, cryoglobolinemia, or infection)
Any size(pseudovasculitis)- APL synd, Embolic phenomenon (eg those associated c myxoma), Endocarditis (bacterial or marantic), cholestrol embolism, drugs (eg amphetamines)
In all of the above check for complement C3 C4, most of them normal x low in urticarial vasculitis and variable in PAN, Leukocytoclastic, Systemic rheumatic disease, Endocarditis
Type of cryoglobulinemia
- Monoclonal Ig eg Waldenstrom, myeloma, lymphoma
- Monoclonal Ig M & polyclonal Ig G eg Hep C B, EBV, Bacterial/Parasitic infection
- Polyclonal Ig G and Ig M eg SLE, Hep C, Lymphoma
Stroke Cerebral Veins Thrombosis Cerebral Veins And Sinuses Thrombosis
- in youngs after NV dehydration
- in females after OC start or obstetrics ward after sz esp 3rd trimester or peripartum
- In hypercoagulable states
- Head injury, Jugular cath, NES, After LP
- Infections mastoiditis, sinusitis, meningitis
- Systemic diseases eg SLE, Wegner, APL syndrome, Nephrotic synrome, Leukemia, Polycythemia
- Severe HA, Sz, W or Numbness, Eye signs, Deep sinus thrombosis causes bil thalamic lesions manifest as delirium, amnesia, mutism
- CT hemorrhagic infarct in multiple arterial territory, Hyperintense signal in sinus or cortical vein (Cord sign); CT angio or venmogram, MRI/MRV, Cerebral angiography (Tortuous or Corkscrew veins)
Stroke Hemorhage Lobar hemorrhage:
Hemorrhagic mets-renal,melanoma,choriocarcinoma,thyroid
The pathognomonic feature of high intracranial pressure and transtentorial herniation is a wedge of pressure necrosis in one or both parahippocampal gyri. Hemorrhagic infarction due to entrapment of the posterior cerebral artery, and entrapment of the third cranial nerves also frequently occur. Secondary brainstem hemorrhages and infarctions are maximal in the midbrain and pons, and rarely extend to the medulla(Durret hemorrhage).
Sturge-Weber disease is characterized by a meningeal vascular malformation and calcification in the second and third layers of the underlying cortex. pt can have hemangioma of chroid of the eye.

- Berry Saccular aneurysm causes
AD Polycystic kidney
Ehlers Danlos
Neurofibromatosis type I
Coarctation of Aorta
Fibromuscular dysplasia
Most around A1 M1 Pcomm
-Vascular malformation
AVM nonfunctional brain tissue can besafely removed
Cavernous angioma no nervous tissue no feedind artery no shunting in cerebellum pons and subcortical
Venous angioma functional paranchyma within
Capillary telengectesia in pons and rarely hemorrhage
Foix Ala jouan ine disease = venus angioma of spinal cord causing myelomalacia mostly lumbosacral cord and slowly progressive fnd
Stroke Stroke Hypercoagulable states:
- Pr C S def functional
- Antithrombin III
- Factor V Leiden mutation
- Prothrombin gene mutation G20210A
- Dysfibrinogenemia, FSProducts
- Homocysteine >15
- APL Anticardiolipins Lupus AC
next stage tests
- Plasminogen activator inhibitors
- UA and fibrinopeptide A assay to evaluate renal source for thrombus
- FSProducts and D dimer to evaluate the stage at which clotting abn occured.
- Peripheral blood smear
- Hepatitis profile to evaluate intrinsic liver disease.
Spontaneous or traumatic dissections occur most frequently in the carotid artery at the neck. Vertebral artery dissections may occur after chiropractic manipulations of the neck. or any neck injury Karate, Roller-Coaster
Alexia without agraphia follows combined damage to the dominant medial occipital region and the inferior fibers of the splenium of the corpus callosum. This is in the distribution of the posterior cerebral artery.
This non-contrast CT reveals a hyperdense tubular region in the proximal segment of the left middle cerebral artery (MCA), consistent with acute thrombosis (arrow). Also noted are subtle left cerebral sulcal effacement, hypodensity of the left basal ganglia, frontal, anterior parietal, and superior temporal lobes. These findings are consistent with an acute MCA infarction. This so-called dense MCA sign or hyperdense MCA sign has been correlated angiographically with embolic or atherothrombotic MCA occlusion. The hyperdensity is most likely due to either calcific or hemorrhagic components of the acute plaque. The hyperdense MCA sign is nonspecific when present in isolation. False positive hyperdense MCAs have been noted in asymptomatic patients with high hematocrit or calcific atherosclerotic disease; these are usually bilateral.
Kennedy- spinal/bulbar muscular atrophy, LMN ss esp in cranial nerves plus dec libido, testicular atrophy, dec FSH,LH, gynecomastia, F asymptomatic, dx by DNA, CAG repeat
Miller-Dieker synd type I lissencephaly ch 7 del
type II c congenital muscular dystrophy auto recessive pattern.
Claude synd-dorsal midbrain tegmentum injury with involvement of 3rd nucleus, red nucleus, brachium conjunctivum SCP
Depressed fx
compound when skin laceration
penetrating when dura is torn
Epidural more arterial lens shaped and more with lucid interval c/t SDH.
if fresh SDH maybe isodense and be missed on CT.
Contrecoup contusions occur in the brain away from the point of impact and do not directly underlie the site of skull fractures. Orbital surfaces of the frontal lobe are the most common location and contrecoup contusions at this site usually occur following a fall on the occiput with the sudden
deceleration of the head. Parasagittal contusions, also called gliding contusions, occur in association with diffuse brain damage and diffuse axonal injury.
dec ICP
Midazolam Versed is the best b/o less hypotension shorter sedation
Pentobarbital Propofol more hypotension dec CBF
Fentanyl Morphin worst
blunt head trauma>carotid cavernous fistula> prptosis, chemosis, ophthalmoplegia
ICP Monitor/Treatment
if GCS>7
if GCS <7 ICP Monitor and can use hypertonic saline 2 or 3%, intermittent boluses of 250-300 cc to keep Na between 145-155
first tier for management of ICP
- tx hyperthermia >37.5
- sz prophylaxis for one week
- head elevation 15-30 degree
- avoidance of juglar venus outflow obstruction: head midline s improperly fitting cervical collar
- sedation/analgesia + pharmacological paralysis regimn
- adequate xygenation, hb, airway, mech vent, O2
- venus resuccitation avoid hypovulomeia
- CSF drainage ventricular catheters
- hyperventilation to obtain PaCO2 30-35 mmHg
- Manitol 1 g/kg serum osmolality 320
Manitol 1 g/kg IV over 10 min then 0.25 g/kg IV Q6H
- possibility of surgical mass considered repeat CT
- hyperventilation to PaCO2 26-30 mmHg
- hyperdynamic therapy high euvolemia c induced htn to support CPP>60 mmHg
- repeat manitol
- barbiturates pentobarbital coma
- craniatomy

HTN control labetolol 0.5mg/min drip titrate to max of 2 mg/min to keep SBP 150-170
CSF Analysis
1- pr, glu, vdrl
2- cells, cytology
3- Ag, Crypto Ag, GS, Cx viral, bacterial, fungal, TB
4- save for future studies
MS Screen
60 alz, vascular, lewy body, FTD and the rest about 10 percent
above age 85, 50 percent demented.
FTD frontal behavior dysexecutive or temporal primary progressive aphasia
common side effects
NV, Cramp, rhinorhea, bradicardia avoid in pt with sicksinus synd or bradydysrhythmia
Vivid dreams when given at night to reduce NV
no Benadryl no OTC sleep aid
Avoid Elavil Oxybutinin
Fish oil omeg 3 acid
Dimebon new drug
Most not all go to AD.
Vit E not used anymore bo cardiotoxicity
Donezepil, behavioral therapy and compensation may help.
halucination paranoid irritability
CEI not proven effective
- clonopin ativan xanax
- SSRI Celexa Lexapro Zoloft
- Seroquel 12.5 to 25 mg bid less eps confusion fall ct Resperadal and zyprexa. Go slowly
- trazodone 25 or 50 mg qhs for sleep
check for uti, enviromental trigers, sleep awake cycle, change one medications at a time
phosphatydyl serine not sure
CholinEstrase inhib
Donepezil start 5mg then after 2 weeks 10 mg
vit e
NSAIDs COX2 inhib
Memantin NMDA antagonist
Neuroleptics for agitation, delusion, hallucination
haldol 0.5-2 mg/d qhs or bid
zyprexa 2.5-7.5 /d enhance cholinergic transmission
seroquel low EPs effects
diphenhydramin 25-50 qhs
Ambien 5-10 qhs
ativan 0.5-1 mg up to tid
Xanax 0.025-0.5 mg qd or bid
Zoloft 50-100 mg qd
if slow Prozac 20 mg qd
if anxiety Paxil
with heart disease Lexapro
- Amitriptyline 50 mg qhs
- Flexeril 10 mg tid
- Neurontin 800 mg tid
- get PT/OT
- Flexion Extension Xrays of back to evaluate function and mobilty
- MRI of back
Mental status changes
localization- bil cerebral hemisphere or RAS
structural- dementia, vascular dementia, stroke, SDH
met/toxic- HE, ResF, RenalF, hypothyroidism, alcohol, wernicke
electrical- subclinical sz, triphasic waves of HE
Meds- anticholinergic, BNZD, narcotics
MRI c dementia protocol
LP CSF vdrl, herpes pcr
Minimize sedation/narcotics
Correction of met/toxic/inf per primary team
check TSH, FT4, RPR, ANA, ESR, B12, FA, homocysteine for dementia
can not tolerate vasoconstrictors triptans or risk for rebound with opioid analgesic do this
- Mg SO4 IV 1 gram over 1-2 h or
- Depacon 500 mg IV over 15 min can repeat after 1h
- Vit B2 400 mg po qd response may take 3 months
rule of 4-6 week to try new preventive med and at least continue it for 4-6 months if effective before change to another preventive med
AEDs good for complicated or basilar migraine eg lamictal, depakote in children or complicated migraine.
Abortive tx
- apap=tylenol
- asa
- NSAIDs ketorolac IV vs Cox2 inhib
- Triptan
- Ergots cafe ergot or DHE
- Depacon 500 mg over 15-30 min
- MgSO4 1 gram over 1 hour in for CAD or basilar migrain
- Droperidol 2.5 mg iv
Compazin 12.5 mg iv
chlorpromazine 12.5 or 25 mg watch for orthostasis
- Midrin
- Supp/ cafeine 150 mg, apap 1000 mg, promethazin 25-50 mg combined
- Narcotics
- Lidocaine 4% 1/2 cc in each nostril same side of HA
Raskin and Lenaerts Suppository:
1) Acetaminophen 1500mg or
Naproxen 750mg
2) Caffeine 150mg
3) Metoclopromide 10mg or
Phenergan 50mg
mix into suppository
(Innovative Pharmacy Solutions)

Raskin Protocol: EKG
1) Reglan 10mg IV over 60 sec.
2) Wait 5 min.
3) Dihydroergotamine mesylate (DHE) 0.5mg IV over 60secs.
4) Wait 5 min.
5) DHE 0.5mg IV over 60secs.
-Repeat q8hrs x3, then q8hrs PRN.
-Give Doxepin 50mg PO q4hrs PRN.
6) Doxepin 50mg PO qhs
Status migrainousus
In pregnancy
use mg, opiates (max 2 days/week, 20 no refill)or antiemetics (compazine)
if fail may use triptan but pt should be in registry
prevention inderal, cyproheptadin, elavil
In menstrual migraine use Frova or continous estrogen or u can use 5 days of Relapex bid or Axert bid for 5-7 days
Co enzyme Q and melatonin newer tx, melatonin in high doses vasoconstrictive.
Botox injection works.

Alternative therapy in migraine
- B2
- B12
- Petadolex
- Feverfew
- Botox about 100 u spread bil q3months follow the pain or fixed points or combination of both
- Biofeedback, relaxation, massage, physical therapy
Status migranosous tx
- Raskin
- IV Depacon 250 over 5 min or 500 over half hour max 750-1000/day
- Droperidol 1 mg IV
- Thorazine 25-50 mg IV watch hypotension
when they hit the floor amitrip or doxepin 50 mg q4h for 3 days and then for total dose of 200-300 mg/day.
For withdrawal/rebound HA-
if on butalbital use Phenobarb
if on bnzd use clonazepam
if on narcotics use methadon
also put them on preventive tx and can also use medrol dosepack, compazine supp
intractable HA usually drug induced use long acting agent Frova and stop offending agent and replace with long acting agent.
Internet sources
30 mcg IM QW c ancillary supplies
28 or 84 days
Avonex can be used every 5 days
Neuropathy 1
Anti-MAG polyneuropathy- chronic symmetric sensorimotor demyelinating polyneuropathy associated c paraproteinemia
IVIG, PE, INF alpha, chlorambucil
Rituximab: monoclonal ab against CD20 Ag on B lymphocytes ( used to treat B cell lymphoma and dec 90% of peripheral B Lym in 3 days)
used qweek for 4 weeks dec anti-MAG titer by 52% (M & N 27:611-615, 2003)
Parkinson diseas
Sinemet for old pt
Dop agonist for young pt, may have neuroprotective effects,
Stalevo 50-100-150 based on levodopa dose
Sinemet 25/... tid at least to have effective carbidopa effect
Side effects: sudden sleep attack, NV
Pramipexole- valvulopathy
Mirapex drug of choice
in children
depakote 10 mg/kg/day after 2-3 days 15 mg/kg/day
topomax 5-9 mg/kg/day
dilantin/pb 20 mg/kg/day
maintenance dose 5 mg/kg/day for pb can be given divided dose bid
Minimum effective dose
tpm 100 day
Lam 150
Keppra 1000 mg a day
tpm lam good for both partial generalized epilepsy
lev zonesamide effective also for generalized sz.
less interation gbp lev pgb
oc interaction tpm
cbz oxc reduce oc efficacy
lmg become less effective with oc
oc reduce lmg level by more than 50 lamictal no effet on oc
less sedation and cognitive effect lmg
weight tpm zonisamide
depression cbz lmg oxc
anxiety gpb lyrica vpa
bipolar lam top oxc
- flexion extension x rays to rule out bony trauma or osteomyelitis or disk
- MRI of brain for tumor thalamic lesion or MRI of c spine for disc
- CT of neck to r/o retropharyngeal abscess
Botox type A bind to receptor on motor nerve terminal and inhibits release of AC
Myobloc type B cleaves synaptobrevin which is the pr complex responsible for docking/fusion of synaptic vesicle to presynaptic membrane.
Lorazepam, Klonopin, Valium
Artane trihexiphenidyl 2,5 mg tab
start half tab 1 mg increment 1 mg q3-5 days to max 2 mg tid
SE- constipation, glucoma, GI obstruction, PU, BOObstruction
it is centrally acting anticholinergic that diminish muscle spasms.
there is acute form of torticollis called acute wryneck in young adults symptomatic tx c heat, massage, supportive cervical collar, muscle relaxants and analgesics.
Treatment Neuralgia Neuralgia
Occipital neuralgia
Marcaine (bupivacaine 0.25%)
12.5-25 mg or 5-10 ml
Xylocaine ( lidocaine 1%)
for infiltration and nerve block
Dexamethasone 4mg/ml
30 ml in multiple dose vial

0.5 cc of 0.25% marcaine and 0.5 cc of decadron (4mg/cc) 2 mg injection with 3 cc syringe and 25 guage 1 1/2 inch needle
Treatment Stroke ICH and SAH
- hyperventilation to obtain PaCO2 30-35 mmHg
- Manitol 1 g/kg serum osmolality 320
Manitol 1 g/kg IV over 10 min then 0.25 g/kg IV Q6H
- for HTN control drug of choice- Nicardipine (inc HR, Coronary vasodilation, no effect on cardiac output), Labtolol, Esmolol, Enalapril (takes longer to act), Nitroprusside (IC venodilation, inc ICP, cynide toxicity)
labetolol 0.5mg/min drip titrate to max of 2 mg/min to keep SBP 150-170
Goal Below SBP180 DBP110 MAP130
Securing aneurysm
surgical clipping titanium
Tx of HCP 1/2 pts need EVD acutely or VPShunt later on (EVD should be removed before 2 weeks)
(Nicardipine better for vasospasm but didn't improve outcome so Nimodipine may have neuroprotective effect)
Timing of aneurysm surgery better be in first 36h esp if they came wiyh highgrade of Hunt Hess Scale
Importance of prognostication
decision making based on individual, disease process and societal level
CM Fisher classification of SAH
I no blood in CT
II blood layer<1mm
III >1 mm
IV intrcerebral intraventricular
lethargy dec LOC grade 3
unruptured grade 0
overall mortality of SAH 20%
Ogilvey Carter scale
Is pt over 50
Is SA >1mm thick on CT
Is aneurysm >10mm or giant >25mm in pcom
Is pt comatose
1 point for each of above.
Vasospasm most commonly present with dec LOC, first rule out pt is not hyponatremic, dec glu, dec O2, no evidence of HCP, no evidence of EVD infection or ventriculitis.
inc risk in 4-14 days after SAH.
tx of vasospasm
3H hemodilution, hypertensive, hypervolumia
otherwise Nimodipine 60 mg q4h for 21 days.
Hunt-Hess SAH grades
I asymptom minimal ha or nuchal regidity
II mod to severe ha, no FND x possible cn 3 palsy
III drowsiness, confusion, FND
IV Stupor, HParesis
V Coma, veg decerebrate

cerebellar more than 3 cm with brain stem compression or hcp
lobar hemorrahge within 1 cm of surface
Treatment Stroke Stroke supportive care
- Dysphagia
solid-pureed diet
fluid- honey, nectar and lastly thin liquid fluid
- DVT scd, heparin sq, ted hose, lovenox study
- GI prophylaxis pepcid
- TF c free water
- Perineal care cleaning 2 a day
- Bowel care colace tid, dulcolax
- Bladder care dc foley care, check pvr if > 300 ( normal people>150 cc) in out cath q6h
- Cough chest PT and postural drainage
- for HTN
Enalapril 0.625 mg IV Q6H hold if SBP is less than 140