1. Metabolic - B12
2. Autoimmune - SLE, sarcoid, etc.
3. Infections - Lyme dz, HIV, PML, syphilis
4. Vascular - vasculitis
5. Genetic - leukodystrophies
6. Structural - syrinx, SC compression
7. Neoplastic - CNS lymphoma

• Age of onset: usually 20 - 40 yo
• Gender: F:M is 2-3:1
• Geography: incidence increases with distance from equator

Incidence: 8500 - 10,000/ year

Prevalence - 350 - 400K in US

General population: 0.1% (1:1000)

 Sibling: 2-5% (1:20-50)

Identical twin: 33% (1:3)

Mom/dad: 1-2% (1: 50-100)

Immune-mediated inflammation of CNS myelin causing areas of demyelination (plaques).

Mediated by autoreactive CD4+ T cells that bind to MS antigens.

Ag-binding leads to cytokine secretion and amplified inflammatory response which causes myelin, oligodendroglial, and axonal injury.

1. Symptom management
2. Exacerbation management: exclude infection, tx with IV methylprednisone or dexamethasone, plasma exchange
3. Modify/reduce relapses (immunomodulator therapy)

1. Decrease relapses by 1/3
2. Decrease severity of relapses
3. Decrease new and enlarging T2 lesion burden
4. Decrease new gadolinium enhancement
5. Prevent disability???

1. High MRI lesion burden @ 1st episode
2. Moderate/severe disability at 5 years
3. Progressive clinical course from onset
4. Male sex
5. Late onset (>40 yo)
6. 2+ relapses in 1st year

Simple: no altered consciousness. May have a postictal neurologic deficit, usually resolves within 24 hr. Can be confused with acute stroke.

Complex: there is altered consciousness. Usually temporal lobe (70-80%) with bilateral spread. Often there's hallucination, deja vu, and automatisms. Postictal confusion/amnesia is characteristic.

LEFT frontal: aphasia, head deviation to right, right hemiparesis.

RIGHT frontal: head deviation and hemiparesis on the left

1. Amnesisa
2. Automatisms (ex. picking movements, lip smacking)
3. Staring

1. FIRST - identify seizure type or epilepsy syndome.
2. Monotherapy is best. Titrate slowly
3. If 1st drug fails, try a second drug. Slowly titrate 2nd while tapering off 1st.
4. Consider: age, sex, lifestyle, comorbidities, meds, drug pharmacokineticcs. 
5. Discuss tx & alternatives with pt and family. 
6. Drug levels are guidelines and should not be strictly used to influence dosing.
7. If 2 adequate trials of monotherapy fail, refer to seizure specialist.

1. Loosen tight clothing of patient, lie him down on his side, and protect from hitting hard or sharp objects
2. Do not place anything in patient's mouth
3. Do not restrain patient.
4. "Wait the seizure out" - if tonic-clonic phase lasts >5 min, call EMS
5. Do not give anything by mouth unless full consciousness is achieved.

1. Don't drive for 3 mo after last seizure (WI law)
2. Take showers instead of baths
3. Don't climb ladders or work from heights
4. Avoid open flames or bodies of water
5. Don't operate heavy machinery/dangeous equipment.

1. Women with seizure d/o, esp. temporal lobe epilepsy, are prone to PCOS and anovulatory cycles.
2. Women on enzyme-inducing anticonvulsants and OCPs may have lowered efficacy of OCPs. Women of child-bearing age should take folic acid.
3. ER and PR receptors are also found in the brain. ER has a pro-convulsant effect & PR has an anticonvulsant effect. Hormonal changes influence seizure frequency, and seizures may increase before ovulation and at the onset of menstruation (high ER levels).

1. Altered GI physiology - variable gastric pH and emptying times, constipation.
2. Decreased serum albumin and altered protein binding
3. Impaired oxidative metabolism
4. Decreased GFR
5. Altered bone metabolism

1. Drug withdrawal (MC is missed meds, also alcohol, benzos)
2. Toxin ingestion (cocaine, amphetamines, TCAs/drugs that lower seizure threshold)
3. Electrolyte disturbance
4. Hypoxia (including ischemic or hemorrhagic stroke)
5. Intracranial infxn
6. Structural brain lesion (trauma, infarct, bleed, tumor).

Note: these are common causes of provoked seizures (i.e. NOT epilepsy) in general., not just SE

1. ABC's of resuscitation-Airway, Breathing, Circulation. Also ensure that full resuscitation facilities are ready in case of CV/resp arrest.
2. Administer lorazepam 1 mg/kg IV
3. Continuous ECG and oximetry
4. Draw blood for glucose, ABG, toxicology, CBC, electrolytes, anticonvulslant levels, etc.

1. Cardiac arrest
2. Respiratory failure
3. Autonomic dysfunction (hyperthermia, hypersecretion)
4. Metabolic dysfunction (acidosis, hyperkalemia, volume depletion)
5. Rhabdomyolysis
6. Renal failure
7. DIC (?)
8. Vertebral fx
9. Epileptic encephalopathy

1. Diplopia
2. Dizziness/Disequilibrium
3. Dysphagia
4. Dysarthria

Sx - nuchal rigidity, NV, HA.

Kernig's sign: inability to completely extend the leg when sitting or lying with the thigh flexed upon the abdomen; when in dorsal decubitus position, the leg can be easily and completely extended.

Brudzinski sign - flexion of the neck caues flexion of hip & knee

1. CT

2. LP

*CT is done 1st, because if there's an abscess or mass, LP can cause herniation.

One half of spinal cord is affected (including STT, CST, and DC).

Results is ipsilateral UMN signs (ex. hyperreflexia) and loss of position & vibration and contralateral loss of pain and temp.

Cona medullaris - symmetric sensory loss.

Cauda equina - asymmetric sensory loss.

Also: Pure cona lesions are rare. Cauda lesions present as LMN dz and more often painful (multiple radiculopathies). Both can have urinary and bowel dysfxn sx. 

1. Acute inflammatory demyelinating polyneuropathy
2. Ascending paralysis
3. Autonomic neuropathy
4. Arrhythmias
5. Albuminocytologic dissociation = CSF protein level > 55 mg/dL with little or no WBCs.

Miller-Fisher variant

• Triad: arreflexia, ataxia, ophthalmoplegia
• Often CN involvement
• GQ1b Ab test
• same LP (albuminocytologic) as GB

Defect in dominant parietal lobe.

Signs: agraphia, acalculia, right/left confusion, finger agnosia

• HTN (lipohyalinosis can lead to microaneursyms and rupture) - MC cause of hemorrhagic stroke
• amyloid angiopathy - lobar hemorrhages, elderly
• drug abuse
• anticoagulation/thrombolytics, coagulopathy
• trauma
• vascular malformation: AVM, aneurysm
• neoplasm
• venous sinus thrombosis
• eclampsia 
• hemorrhagic transformation of ischemic stroke

1. CT shows ICH or SAH
2. History of ICH
3. Recent stroke (3 mo), GI bleed (3 wks), surgery (2 wks), noncompressible artery puncture (1 wk) - can consider intra-arterial tx
4. Plt <100K, INR > 1.5, elevated PTT
5. Uncontrollable bp (>185/110 w/ tx).

IV tPA: 3 - 4.5 hrs

Intra-arterial: up to 6 hrs

Mechanical intervention: up to 8 hrs

1. Maximize perfusion (consider tPA if w/in 3 hrs, do not decrease bp)
2. Limit further neurologic damage by maintaining blood sugar and normal temp
3. Limit complications - DVT prophylaxis (SQ heparan), early rehab, beware of seizures (but no routine prrophylaxis).  Look out for depression and dysphagia (aspiration).
4. Identify source - MRI, echo, CTA, MRA, cartoid US, etc (May need to do this in orer to do some of #3).
5. Prevent recurrent stroke - anticoagulants if source is embolic, otherwise do antiplatelets. Treat RFs aggressively (HTN, smoking, DM, hyperlipidemia)

What mimics of stroke should always be ruled out before doing tPA? (6)

1. Focal seizure
2. Migraine (aura, complicated0
3. Tumor
4. Trauma 
5. Hypoglycemia
6. Psychogenesis

* these can also cause focal, acute deficits = characteristic of stroke

Temporary defiict that resolves fully (< 1 hr) AND brain imaging must be negative.

"Brain-gina"

[Classic/old definition: neuro deficit attributed to ischemia lasting <24 hrs.]

1. Pure sensory - thalamus
2. Pure motor (can include dysarthria) - posterior limb of IC, midbrain, pons, medulla (CST)
3. Mixed sesnory/motor - thalamocapsular
4. Clumsy hand dysarthria - unilateral hand weakness (subtle) + dysarthria; pons
5. Ataxic hemiparesis - cerebellar and motor sx on same side of body; pons, capsule, midbrain, or ACA distribution 

• Lipohyalinosis of small perforating arteries
• Leads to progressive narrowing and eventually thrombotic occlusion of these arteries
• lacunae in periventricular white matter
• Caused by endothelial damage d/t chronic HTN and DM

Hemorrhagic strokes are more likely to be lethal than ischemic. 

Hemorrhagic: 30-50% die, only 20-30% will be independent in 6 mo.

1. Head CT and repeat 6-12 hrs later - 40% expand in 1st 24 hrs, may develop hydrocephalus, elevated ICP d/t mass effect
2. Check for abnormal PT/PTT/platelets, and correct accordingly.

Note: to prevent complications, use SCDs until pt is stable, then start SQ heparan/lovenox - usually after 48-72 hours.  

• usually from deceleration and brain impacting bony prominences of skull
• focal deficits correlate with location of contusion
• continued bleeding/edema can cause increased ICP
• Noncontrast CT will show area with surrounding edema

• more frequently occurs d/t falls or assault (vs MVA), but may occur with minimal/no hx of trauma 
• tearing of bridging vv btwn cortex and dural venous sinuses
• CT has crescent-shaped lesion, does not cross midline

• Can be acute, subacute, or chronic.
• Sx may include altered mental state, HA, contralateral hemiparesis, and focal neuro deficits that appear over days to weeks
• some cases of subacute or chronic may be managed conservatively
• most acute cases require immediate surgical drainage through burr hole
• 50-90% mortality
• mortality correlates with age and ICP. 

• Usually caused by torn artery after skull fx, MC = middle meningeal a.
• Classically associated with momentary LOC, lucid interval of minutes to hours, then neuro deterioration.
• CT - lens shaped lesion, limited by sutures
• Tx = immediate surgical evacuation
• Mortality = 5-55%

• mechanism: brain impacts bony prominence of skull (like contustion)
• usually involves frontal or temporal areas
• Reaches max size in 12 hrs
• CT - check for herniation
• most require surgery evacuation if mass effect is significant; otherwise may be treated similarly to SAH.

• By definition: clinical dx; must be NO imaging findings.
• A mild diffuse (vs focal) type brain injury
• transient alteration of consciousness w/ confusion/amnesia
• does NOT require Loc

• Disruption of axons d/t angular acceleration and shear forces at gray-white border
• LOC > 6 hrs, significant amnesia
• MRI - microhemorrhages in white matter
• Tx = supportive; control ICP (poor px)

1. Hypotension
2. Hypoxia
3. Inflammatory cascades
4. Excitotoxic NTs (glutamate)
5. Cerebral edema
6. Elevated ICP

1. Mass
2. Edema
3. Blocked CSF drainage
4. CSF overproduction
5. Bleeding

1. HA - esp one that is worse upon lying down and improves when sitting up. Worse after waking up in morning
2. NV
3. Papilledema
4. Altered mental status
5. BS compression & focal neuro signs
6. Death from herniation

• Poor outcome is associated with increasing ICP (severity) and prolonged duration of elevated ICP 

CPP = MAP - ICP

Goal: CPP > 70 mmHg and ICP < 20-25 mmHg

• Drain with intraventricular catheter - can be done in acute TBI
• Drain with lumbar catheter - not recommended in acute TBI, but can be be done in non-obstructive hydrocephalus.

1. reduce mass or parenchymal volume
2. reduce CSF (catheters, corticosteroids)
3. reduce blood (includes sedation/barbiturates, hyperventilation, osmotic diuresis, hypothermia)
4. expand cranial cavity

• Prophylactic HV after brain injury should be avoided.
• HV for brief periods of acute neuro deterioration, or for longer periods of ICP that are refractory to sedation, paralysis, CSF drainage, and osmotic diuresis is okay.
• Goal range of PaCO2 is ~25 - 30 mmHg. 

Mechanism: Can restore damaged areas of vascular permeability, decreased CSF production, decreased free radical production and damage.

Excellent for vasogenic edema (ex. tumor), but not useful for TBI, stroke.

• Hypothermia causes decreased oxygen demand. This leads to vasoconstriction, decreased blood volume, decreased ICP
• May act as an anticonvulsant.
• Decreases concentration of excitatory aa and lactate
• Anti-inflammatory effects
• SE: decreased CO, increased systemic vascular resistance, thrombocytopenia, bradycardia, pneumonia

1. MC complication = development of epilepsy (~30% occurence after single episode of SE)
2. Mesial temporal sclerosis - affects memory/behavior. Seen on MRI
3. Neurologic injury: gluatmate activation of NMDA receptors leads to apoptosis
4. Chronic encephalopathy - brain atrophy

1. Disc degeneration - chemical changes associated with aging causes discs to weaken (no herniation). Most people have this with aging.
2. Prolapse - disc changes with slight impingement on the spinal canal (aka bulge or protrusion).
3. Extrusion - gel-like nucleus pulposus breaks through the annulus fibrosus but remains within disc
4. Sequestration - nucleus pulposus breaks through annulus and enters the spinal canal.

• Sciatic nerve = L5/S1
• shooting pain from the posterior hip, down the leg, toward the heel and the inner foot (L5)

1. Knee jerk: L4
2. Ankle jerk: S1

1. musculoligamentous strain
2. degenerative disc disease
3. herniation of nucleus pulposus
4. spinal stenosis
5. spondylolisthesis (misalignment)
6. scoliosis

In both cases: person gets weak when walking and must STOP and rest before he starts walking again.

Difference: if person is able to walk for prolonged time when leaning on walker or grocery cart = spinal stenosis (not claudication).

1. focal neurologic deficits (ex. foot drop, hyperreflexia, weakness in one area)
2. immunosuprression
3. fever/infection
4. Hx of cancer or recent rapid unintentional weight loss
5. Hx of trauma (may be very minor trauma in elderly)

1. Acute phase - pain reduction, control inflammation and spasm, prevent deconditioning
2. Restorative phase  - normalize ROM, correct biomechanical deficits, build strength and flexibility to achieve dynamic spine stablization.
3. Maintenance phase - sport/activity-specific trainng; stop medication mgmnt. 

1. immediate onset of neurological deficits
2. deficits are consistent with SC involvement at the level of injury
3. complete neurologic recovery within 72 hours (3 d)

concussion = mildest form of SCI, often sports-related

1. Myelomalacia - edema and softening of SC evident on MRI. Indicate cell death and permanent neuronal damage.
2. Hematomyelia - blood in SC

High dose methylprednisolone should be given:

• if initiated within 3 hrs, should be continued for 24 hrs
• if initiated between 3-8 hrs, should be continued for 48 hrs.
• Should NOT be given after 8 hrs
• Should NOT be given in pt w/ SCI d/t gunshot wound.

The methylprednisolone reduces secondary damage. 

Complication: immunosupression lasts for days - high risk of infxn, esp pneumonia

• occurs almost exclusively in cervical cord
• MC spinal syndrome after traumatic SCI (elderly, falls)
• Weakness of UE>>>LE

ASIA A - complete = no sensory or motor function preserved in lowest sacral levels

ASIA B - incomplete sensory, complete motor. Some sensory preserved below neurological level.

ASIA C - incomplete motor. Some motor fxn preserved below neurological level, but most muscles < 3/5.

ASIA D - incomplete motor; Some motor fxn preserved below neurological level; most muscles =/> 3/5

ASIA E - normal (accounts for <0.5% after SCI).

1. Pneumonia

2. Coronary heart dz

• DVT - incidence up to 100%. 
• Highest risk in first 2 weeks
• Best prophylaxis is LMWH given for 8-12 wks for ASIA A or B and for 4-6 wks for ASIA C or D
• Other prophylactics: coumadin, SQ heparin, greenfield filter (prevent migration to lung), compression stockings/boot.

Syndrome characterized by sudden increase in bp, reflexive bradycardia, and anxiety. Patients have pounding HA, mydriasis, flushing/sweating. Below level of injury may have pallor, cool extremities, piloerection.

• Goal is to salvage the penumbra = area surrounding infarcted area that is ischemic, but not yet infarcted
• Reperfusion is achieved by:

1. IV tPA
2. internventional catheter methods/endarterectomy
3. Hypertensive tx (phenylephrine)
4. Hemicraniectomy (when pt is at risk for herniation, this is a life saving measure but does not treat the stroke)

Causes of cardioembolic stroke (5)

Which is MOST common?

1. Atrial fib - MC
2. prosthetic heart valves
3. mural thrombi (DCM with reduced EF; post MI wall motion abnormalities)
4. Endocarditis
5. PFO - venous clots. Esp. for stroke in younger people

1. Mostly supportive tx: lower bp, decrease/prevent edema
2. Immediate tx: activated factor VII clotting factor can be given up to 3 hrs after ICH to limit hematoma expansion - limited by risk of thrombosis (DVT, MI, stroke). 

DVT prophylaxis once patient is stable.

• Rupture of vessels in SA space. 
• Causes: aneurysm, trauma, AVM
• CT shows blood in sulci

1. Secure aneurysm to prevent re-bleed (coil>clip)
2. Supportive Care
3. Prevent vasospasm - Triple H and CCBs (nimodipine). Triple H includes making patient hypertensive, hypervolemic, and hemodiluted.

1. Remote symptomatic etiology (ex. remot hx of head trauma)
2. Partial onset
3. Abnormal EEG
4. Overall risk of recurrence after single, unprovoked seizure is 15-30%. 

1. insula*
2. anterior cingulate gyrus
3. hypothalamus

*other insula-localizaing auras: gustatory, abdominal

The following may localize to: 1. dystonic posture,

2. asymmetric tonic posturing, 3. unilateral blinking

• Carbamazepine - imbalance, ataxia
• Valproic acid - weight gain, tremor, hepatotoxicity
• Felbamate - neutropenia
• Topiramate - cognitive decline and kidney stones
• Zonisamide - kidney stones.