Stroke & TIA
Ischemic Stroke
Ischemic stroke (~87%) results from cerebral arterial occlusion causing neuronal death from lack of oxygen and glucose. Mechanisms: cardioembolic (AF, endocarditis, LV thrombus — 20%), large vessel atherothrombosis (25%), small vessel (lacunar — 25%), cryptogenic (30%). Ischemic penumbra = surrounding tissue that is electrically silent but metabolically salvageable — target for reperfusion.
Hemorrhagic Stroke
ICH (~13%): HTN (deep structures — putamen, thalamus, pons, cerebellum), amyloid angiopathy (lobar bleeds in elderly), anticoagulation, arteriovenous malformation. SAH: rupture of saccular (berry) aneurysm (most common); "worst headache of my life"; blood in subarachnoid space; xanthochromia on LP.
Time-Sensitive Criteria
| Intervention | Window | Criteria |
|---|---|---|
| IV tPA (alteplase) | 0–4.5 hours from symptom onset | NIHSS-based; BP <185/110 before administration; no hemorrhage on CT; many exclusion criteria |
| Mechanical thrombectomy | 0–24 hours (selected patients up to 24h) | Large vessel occlusion (ICA, MCA-M1); NIHSS ≥6; salvageable penumbra on imaging |
TIA
Transient Ischemic Attack = focal neurological deficit lasting <24 hours (usually <1 hour) without infarction on DWI MRI. ABCD2 score predicts 2-day stroke risk. All TIAs should be urgently evaluated (treat as minor stroke — start antiplatelet, statin, BP control, work up embolic sources).
Seizures & Epilepsy
| Type | Features | EEG Pattern | First-Line Treatment |
|---|---|---|---|
| Focal aware (simple partial) | Motor, sensory, autonomic, or psychic symptoms; no LOC; Jacksonian march (motor spread) | Focal spike/sharp waves | Carbamazepine, oxcarbazepine, lamotrigine |
| Focal unaware (complex partial) | Impaired consciousness; automatisms (lip smacking, hand gesturing); temporal lobe most common (temporal lobe epilepsy) | Focal temporal slowing | Carbamazepine, levetiracetam, lamotrigine |
| Generalized tonic-clonic | Bilateral convulsion; LOC; postictal confusion; incontinence; Todd's paralysis post-ictally | Generalized spike-and-wave | Valproate, lamotrigine, levetiracetam |
| Absence (petit mal) | Brief (5–30 sec) staring spells; abrupt onset/offset; no postictal phase; children 4–12 | 3 Hz spike-and-wave (pathognomonic) | Ethosuximide (absence only); valproate (+ other types) |
| Myoclonic | Brief muscle jerks; usually morning after waking; juvenile myoclonic epilepsy (JME) in teens/young adults | Polyspike-and-wave | Valproate, levetiracetam; avoid carbamazepine (worsens myoclonic) |
Meningitis
| Feature | Bacterial | Viral (Aseptic) | Fungal |
|---|---|---|---|
| Classic triad | Fever + headache + nuchal rigidity (+ altered mental status) | Fever + headache + nuchal rigidity (milder) | Subacute onset; immunocompromised |
| CSF appearance | Cloudy/turbid | Clear | Clear |
| WBC | >1000 PMNs (neutrophilic) | 100–1000 (lymphocytic) | Lymphocytic |
| Glucose | Very low (<40 mg/dL) | Normal or slightly low | Low |
| Protein | Elevated (>200 mg/dL) | Mildly elevated | Elevated |
| Common organisms | S. pneumoniae, N. meningitidis (young adults), Listeria (elderly/immunocompromised), GBS + E. coli (neonates) | Enteroviruses (most common), HSV-2, mumps | Cryptococcus neoformans (HIV, CD4 <100) |
| Treatment | Empiric: ceftriaxone + vancomycin + dexamethasone (↓ complications); add ampicillin for Listeria (age >50, immunocompromised) | Supportive; acyclovir for HSV | Amphotericin B + flucytosine → fluconazole maintenance |
Parkinson's Disease
Pathophysiology
Loss of dopaminergic neurons in the substantia nigra pars compacta → reduced striatal dopamine → loss of basal ganglia modulation of voluntary movement. Lewy bodies (aggregates of alpha-synuclein) are pathological hallmark. Idiopathic PD is most common; secondary parkinsonism: antipsychotics (dopamine blockers), MPTP, manganese, striatonigral degeneration (MSA).
Cardinal Motor Features: TRAP
Non-Motor Features
- Constipation, anosmia (may precede motor symptoms by years)
- REM sleep behavior disorder (acts out dreams)
- Depression, anxiety (up to 50%)
- Orthostatic hypotension (autonomic dysfunction)
- Dementia (20–30% develop Parkinson's disease dementia)
Alzheimer's Disease
Pathophysiology
Most common dementia (60–80% of cases). Characterized by amyloid plaques (extracellular beta-amyloid Abeta-42 aggregation) and neurofibrillary tangles (intracellular hyperphosphorylated tau protein). Amyloid cascade hypothesis: amyloid deposition is primary driver; triggers tau pathology, neuroinflammation, synaptic loss, and neurodegeneration. Cholinergic hypothesis: loss of cholinergic neurons in nucleus basalis of Meynert → impaired ACh-mediated memory consolidation.
Clinical Stages & Features
| Stage | Features |
|---|---|
| MCI (preclinical/mild) | Memory complaints beyond normal aging; preserved ADLs; hippocampal atrophy on MRI |
| Mild AD | Episodic memory loss (short-term worse than long-term); getting lost; word-finding difficulty; MMSE 20–26 |
| Moderate AD | Needs help with ADLs; behavioral symptoms (agitation, wandering, delusions, sundowning); MMSE 10–20 |
| Severe AD | Fully dependent; loss of speech, incontinence, inability to walk/swallow; MMSE <10 |
Multiple Sclerosis
Pathophysiology
Autoimmune demyelinating disease of the CNS. T-cell mediated attack on myelin and oligodendrocytes → plaques (areas of demyelination and axonal damage) in white matter. Common locations: periventricular white matter, corpus callosum (Dawson's fingers on MRI), brainstem, spinal cord, optic nerves. Onset typically age 20–40; female:male 3:1; more common in northern latitudes.
Clinical Presentations
| Syndrome | Features | Lesion Location |
|---|---|---|
| Optic neuritis | Painful unilateral vision loss, dyschromatopsia, Marcus Gunn pupil (RAPD) | Optic nerve |
| Internuclear ophthalmoplegia | Impaired adduction of one eye with nystagmus of abducting eye; preserved convergence | MLF (medial longitudinal fasciculus) |
| Lhermitte's sign | Electric shock sensation down spine with neck flexion | Cervical spinal cord |
| Uhthoff's phenomenon | Worsening symptoms with heat/exercise (action potential failure in demyelinated axons) | Any demyelinated tract |
| Transverse myelitis | Paraparesis, sensory level, sphincter dysfunction | Spinal cord |
MS Types & Treatment
| Type | Course | DMT Examples |
|---|---|---|
| RRMS (85%) | Relapsing-remitting; most common; complete or incomplete recovery between attacks | IFN-beta, glatiramer acetate, natalizumab, ocrelizumab, alemtuzumab |
| PPMS | Progressive from onset; no relapses; older age; ocrelizumab is only FDA-approved DMT | Ocrelizumab (anti-CD20) |
| SPMS | Follows RRMS; progressive accumulation of disability; siponimod, cladribine | Siponimod, cladribine |