Neurology

01 Neuroanatomy — Brain & Cranial Nerves

Cerebral Cortex — Lobes & Functions

The frontal lobe occupies the anterior third of each hemisphere, bounded posteriorly by the central sulcus and inferiorly by the lateral (Sylvian) fissure. It contains the primary motor cortex (precentral gyrus — Brodmann area 4), the premotor cortex (area 6), and the prefrontal cortex (executive function, judgment, personality, working memory). Broca's area (areas 44–45) in the dominant (usually left) inferior frontal gyrus controls expressive language — damage produces non-fluent (Broca's) aphasia: halting, effortful speech with preserved comprehension.

The parietal lobe lies posterior to the central sulcus and above the lateral fissure. Its primary somatosensory cortex (postcentral gyrus — areas 3, 1, 2) processes contralateral tactile, proprioceptive, and pain input. The inferior parietal lobule in the dominant hemisphere integrates language processing (angular gyrus — area 39 — alexia with agraphia when damaged). Non-dominant parietal lesions produce hemispatial neglect — the patient ignores the contralateral side of space.

The temporal lobe lies below the lateral fissure. It houses the primary auditory cortex (Heschl's gyrus — areas 41, 42), the hippocampus (medial temporal — memory formation), and Wernicke's area (posterior superior temporal gyrus — area 22) in the dominant hemisphere — damage produces fluent (Wernicke's) aphasia: flowing but meaningless speech with impaired comprehension. The occipital lobe is the most posterior, containing the primary visual cortex (area 17 along the calcarine fissure). Unilateral occipital lesions produce contralateral homonymous hemianopia.

Subcortical Structures

The basal ganglia (caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra) regulate motor planning, initiation, and inhibition. The caudate + putamen = striatum (primary input nuclei, receiving cortical glutamatergic input); the putamen + globus pallidus = lentiform nucleus. Degeneration of dopaminergic neurons in the substantia nigra pars compacta produces Parkinson's disease. The thalamus is the relay station for nearly all sensory and motor pathways to the cortex. The hypothalamus controls autonomic function, thermoregulation, hunger, thirst, circadian rhythms, and hormonal release via the pituitary. The limbic system (hippocampus, amygdala, cingulate gyrus) mediates memory encoding, emotion, and motivation.

Brainstem

The brainstem connects the cerebrum to the spinal cord and contains cranial nerve nuclei, ascending/descending tracts, and the reticular activating system (consciousness). Three divisions from rostral to caudal: midbrain (CN III, IV; cerebral peduncles; superior/inferior colliculi; substantia nigra; red nucleus), pons (CN V, VI, VII, VIII; pontine nuclei; middle cerebellar peduncles), and medulla oblongata (CN IX, X, XI, XII; pyramids where the corticospinal tracts decussate; nucleus solitarius for visceral sensation; dorsal motor nucleus of vagus). The medulla contains the vital respiratory and cardiovascular centers — compression causes bradycardia, hypertension, and irregular respirations (Cushing's triad).

Cranial Nerves

Cerebellum

The cerebellum coordinates voluntary movement, balance, and motor learning. Three functional divisions: vestibulocerebellum (flocculonodular lobe — balance, eye movements; lesions cause truncal ataxia and nystagmus), spinocerebellum (vermis + paravermal zones — posture, gait, limb coordination; vermis lesions cause wide-based gait ataxia), and cerebrocerebellum (lateral hemispheres — motor planning, timing; lesions cause ipsilateral limb dysmetria, intention tremor, dysdiadochokinesia). Cerebellar signs are always ipsilateral to the lesion — unlike cerebral hemisphere lesions, which produce contralateral deficits.

02 Neuroanatomy — Spinal Cord & Vascular Territories

Spinal Cord Tracts

Spinal Cord Syndromes

Cerebral Vascular Territories

03 The Neurological Examination

Mental Status

Assess level of consciousness (alert, lethargic, obtunded, stuporous, comatose), orientation (person, place, time, situation), attention (serial 7s, spell "WORLD" backwards, digit span — normal forward is 7 ± 2), language (fluency, comprehension, repetition, naming, reading, writing — localizes aphasia type), memory (immediate recall, short-term at 5 minutes, long-term), and executive function (Luria hand sequences, clock drawing, verbal fluency — name as many animals as possible in 60 seconds; normal ≥ 12). The Mini-Mental State Examination (MMSE) scores 0–30 (normal ≥ 24); the Montreal Cognitive Assessment (MoCA) is more sensitive for mild cognitive impairment (normal ≥ 26/30).

Cranial Nerve Examination

CN II: Visual acuity (Snellen chart), visual fields by confrontation (each eye separately — wiggle finger in each quadrant), fundoscopy (papilledema, optic disc pallor), pupillary light reflex (direct and consensual), swinging flashlight test for relative afferent pupillary defect (APD/Marcus Gunn pupil — pupil dilates when light swings to it, indicating optic nerve damage on that side). CN III/IV/VI: Extraocular movements — trace an "H" pattern; assess for nystagmus, internuclear ophthalmoplegia (INO — failure of adduction on lateral gaze with nystagmus of abducting eye; caused by MLF lesion; bilateral INO strongly suggests MS in young patients). CN V: Sensation in V1, V2, V3 distributions; corneal reflex (afferent V1, efferent VII); jaw clench strength. CN VII: Forehead wrinkling, eye closure, smile, puff cheeks — distinguish UMN (forehead spared because of bilateral innervation) from LMN (entire ipsilateral face). CN VIII: Weber (tuning fork on vertex — lateralizes to conductive loss, away from sensorineural) and Rinne (compare air vs bone conduction). CN IX/X: Gag reflex, palate elevation ("say ahh" — uvula deviates away from weak side), voice quality. CN XI: Shoulder shrug (trapezius), head turn against resistance (SCM — turns head to opposite side). CN XII: Tongue protrusion (deviates toward lesion in LMN), fasciculations.

Motor Examination

Assess bulk (atrophy — LMN or disuse), tone (spasticity = UMN, velocity-dependent "clasp-knife"; rigidity = basal ganglia, velocity-independent "lead-pipe" or "cogwheel" with superimposed tremor; flaccidity = LMN or acute UMN/spinal shock), and strength using the MRC scale:

Test proximal and distal muscle groups in all four extremities. Key patterns: UMN — weakness of extensors in upper extremity (arm extensors, finger extensors, wrist extensors) and flexors in lower extremity (hip flexors, knee flexors, ankle dorsiflexors), giving the classic "pyramidal" pattern. LMN — weakness in specific myotomal or nerve distribution with atrophy and fasciculations.

Sensory Examination

Test light touch (cotton wisp — dorsal columns primarily), pinprick (spinothalamic), temperature (cold tuning fork — spinothalamic), vibration (128 Hz tuning fork on bony prominences — dorsal columns; compare distal to proximal), proprioception (joint position sense at great toe — dorsal columns), and cortical sensation (stereognosis, graphesthesia, two-point discrimination — parietal lobe). Dermatomal patterns suggest radiculopathy; stocking-glove pattern suggests peripheral neuropathy; a sensory level suggests myelopathy.

Reflexes

Grade: 0 = absent, 1+ = hypoactive, 2+ = normal, 3+ = hyperactive without clonus, 4+ = hyperactive with clonus. Hyperreflexia = UMN; hyporeflexia/areflexia = LMN. Babinski sign (upgoing plantar response) = UMN lesion (normal in infants < 1 year). Hoffman's sign (flicking the distal phalanx of the middle finger causes thumb/index flexion) = cervical myelopathy/UMN. Clonus (≥ 3 beats sustained) = UMN.

Coordination & Gait

Finger-to-nose and heel-to-shin test cerebellar function (dysmetria = overshoot/undershoot). Rapid alternating movements (dysdiadochokinesia = cerebellar). Romberg test: patient stands feet together, eyes closed — positive (falls) = proprioceptive or vestibular dysfunction (not cerebellar — cerebellar patients are unstable even with eyes open). Gait patterns: spastic (stiff, circumduction — UMN), steppage (foot drop, high knee — peroneal nerve/L5), waddling (hip girdle myopathy), ataxic/wide-based (cerebellar), magnetic/apraxic (frontal lobe, NPH), festinating (small shuffling steps, forward lean — Parkinson's).

04 Key Terminology

05 Acute Ischemic Stroke Cerebrovascular

Ischemic stroke accounts for ~87% of all strokes. Sudden occlusion of a cerebral artery causes ischemia in the downstream territory. The ischemic penumbra — tissue that is hypoperfused but not yet infarcted — is the target of acute reperfusion therapy. Every minute of untreated large-vessel occlusion destroys ~1.9 million neurons (Saver, 2006). "Time is brain" is literal, not metaphorical.

TOAST Classification — Stroke Etiology

NIH Stroke Scale (NIHSS)

The NIHSS is the standardized tool for quantifying stroke severity (0–42 points). It guides treatment decisions: NIHSS ≥ 6 strongly suggests a large vessel occlusion warranting emergent CTA and potential thrombectomy. Key items:

Acute Management — IV Thrombolysis

Alteplase (tPA) 0.9 mg/kg IV (max 90 mg), 10% as bolus, remainder over 60 minutes. Window: within 4.5 hours of symptom onset (or last known well). The NINDS trial (1995) established the 3-hour window; the ECASS III (2008) extended to 4.5 hours with additional exclusion criteria (age > 80, NIHSS > 25, oral anticoagulant use, history of both stroke and diabetes). Tenecteplase (0.25 mg/kg IV single bolus, max 25 mg) is increasingly used as an alternative — simpler administration, and the EXTEND-IA TNK trial showed non-inferiority to alteplase for LVO with better early reperfusion. Key contraindications: SBP > 185/110 despite treatment, platelets < 100K, INR > 1.7, recent major surgery/trauma (< 14 days), active internal bleeding, intracranial hemorrhage on CT.

Mechanical Thrombectomy

For large vessel occlusion (LVO) — ICA, M1 MCA, and in select cases M2 MCA or basilar artery. Five landmark 2015 trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT) demonstrated overwhelming benefit of endovascular thrombectomy + IV tPA vs tPA alone. Standard window: within 6 hours. Extended window to 24 hours for selected patients with favorable perfusion imaging (core infarct < 70 mL on CTP or DWI, and significant mismatch between core and penumbra) — established by DAWN (2018) and DEFUSE 3 (2018). NNT for good functional outcome (mRS 0–2) is approximately 2.6 — one of the most effective interventions in all of medicine.

Secondary Prevention

Antiplatelet: ASA 81–325 mg daily for non-cardioembolic stroke; dual antiplatelet (ASA + clopidogrel) for 21 days after minor stroke/TIA (NIHSS ≤ 3), then single agent (POINT trial). Cardioembolic (AF): anticoagulation with DOAC (apixaban, rivaroxaban, dabigatran, edoxaban) — superior to warfarin for non-valvular AF; start timing depends on infarct size (small infarct: 1–3 days; medium: 6–8 days; large/hemorrhagic transformation: 12–14 days — the "1-3-6-12" rule). Statins: high-intensity (atorvastatin 80 mg) for all atherosclerotic strokes. Carotid stenosis ≥ 70% symptomatic: CEA or CAS within 2 weeks of event.

06 Hemorrhagic Stroke — ICH & SAH Cerebrovascular

Intracerebral Hemorrhage (ICH)

ICH accounts for ~13% of strokes but ~40% of stroke mortality. The most common cause is hypertensive vasculopathy — chronic hypertension weakens penetrating arterioles, forming Charcot-Bouchard microaneurysms that rupture. Typical locations: basal ganglia (putamen — most common, ~35%), thalamus (~20%), pons (~5%), cerebellum (~10%), lobar (~30%). Lobar ICH in elderly patients suggests cerebral amyloid angiopathy (CAA) — amyloid-beta deposits in cortical/leptomeningeal vessel walls causing recurrent lobar hemorrhages.

ICH Score (prognostic — mortality at 30 days):

Score 0 = 0% mortality; 1 = 13%; 2 = 26%; 3 = 72%; 4 = 97%; 5 = 100%.

Management: Emergent BP reduction: SBP target < 140 mmHg within 1 hour (nicardipine drip preferred) — the INTERACT2 trial showed improved functional outcomes with intensive lowering. Reverse anticoagulation immediately: warfarin → PCC (Kcentra) 25–50 units/kg + vitamin K 10 mg IV; dabigatran → idarucizumab (Praxbind); rivaroxaban/apixaban → andexanet alfa or PCC. Platelet transfusion for antiplatelet-associated ICH is NOT recommended (PATCH trial showed harm). Surgical evacuation: consider for cerebellar ICH > 3 cm with deterioration, or supratentorial lobar ICH with GCS 9–12 and clot accessible (STICH II trial). External ventricular drain (EVD) for hydrocephalus from intraventricular hemorrhage.

Subarachnoid Hemorrhage (SAH)

Nontraumatic SAH is caused by ruptured saccular (berry) aneurysm in ~85% of cases. The classic presentation is "worst headache of my life" — thunderclap onset peaking within seconds, often with nausea/vomiting, neck stiffness, photophobia, and loss of consciousness. Mortality is ~40% overall; 15% die before reaching the hospital. Most common aneurysm location: anterior communicating artery (AComm) (~30%), then posterior communicating artery (PComm) (~25%), MCA bifurcation (~20%).

Hunt-Hess Grade (Clinical Severity at Presentation)

Fisher Grade (CT Appearance — Predicts Vasospasm Risk)

SAH Management: (1) Secure the aneurysm within 24 hours — endovascular coiling (preferred for most locations, per ISAT trial) or surgical clipping. (2) Nimodipine 60 mg PO q4h × 21 days — the only proven agent for preventing delayed cerebral ischemia from vasospasm. (3) Euvolemia (avoid both hypo- and hypervolemia; "triple-H therapy" — hypertension, hypervolemia, hemodilution — is largely abandoned except for induced hypertension for symptomatic vasospasm). (4) Monitor for vasospasm (peak days 4–14): daily transcranial Doppler (MCA velocity > 200 cm/sec = severe spasm), neuro checks q1h. (5) EVD for hydrocephalus. (6) Seizure prophylaxis is controversial — levetiracetam if used; phenytoin is avoided (associated with worse cognitive outcomes).

07 Transient Ischemic Attack (TIA) Cerebrovascular

TIA is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction on imaging. The modern (tissue-based) definition does not use a 24-hour time cutoff — any episode with DWI-positive infarction is classified as stroke regardless of symptom duration. Most true TIAs last < 15 minutes. TIA is a medical emergency: the 90-day stroke risk after TIA is 10–15%, with half occurring within the first 48 hours.

ABCD2 Score — 2-Day Stroke Risk After TIA

Score 0–3: low risk (~1%); 4–5: moderate risk (~4%); 6–7: high risk (~8%). However, ABCD2 has limited sensitivity — current guidelines recommend emergent workup for all TIAs regardless of score. Workup: brain MRI with DWI, neurovascular imaging (CTA or MRA head/neck), echocardiography, cardiac monitoring (telemetry ≥ 24h, consider 30-day event monitor for cryptogenic), and labs (CBC, CMP, lipid panel, A1c, PT/INR).

08 Cerebral Venous Thrombosis Cerebrovascular

Thrombosis of the dural venous sinuses or cortical veins. Unlike arterial stroke, CVT often presents subacutely over days to weeks. Most common in young women (OCP use, pregnancy/postpartum, hormonal factors). Other risk factors: hypercoagulable states (Factor V Leiden, prothrombin G20210A, antiphospholipid syndrome), infections (sinusitis, mastoiditis, meningitis), dehydration, malignancy. Most commonly affected: superior sagittal sinus (~62%) and transverse/lateral sinus (~45%).

Presentation: Headache (>90% — often progressive, worse with Valsalva), papilledema, seizures (~40%), focal deficits (hemiparesis, aphasia), altered consciousness. Diagnosis: CT venography (CTV) or MR venography (MRV) — shows filling defect ("empty delta sign" on contrast CT is classic but insensitive). D-dimer may be elevated but a normal D-dimer does not exclude CVT. Treatment: Anticoagulation with heparin (UFH or LMWH) even if hemorrhagic infarction is present — counterintuitive but supported by evidence. Transition to warfarin (INR 2–3) or DOAC for 3–12 months depending on the underlying cause. Endovascular thrombectomy/thrombolysis reserved for deterioration despite anticoagulation.

09 Seizure Classification (ILAE 2017) Epilepsy

The 2017 ILAE classification replaced the 1981 system. It organizes seizures by three features: (1) onset (focal, generalized, unknown), (2) awareness (aware vs impaired awareness for focal seizures), (3) motor vs non-motor manifestation.

Focal Onset Seizures

Generalized Onset Seizures

10 Status Epilepticus Epilepsy

Defined as a seizure lasting ≥ 5 minutes or two or more seizures without return to baseline between them. Convulsive status epilepticus (CSE) is a life-threatening emergency — mortality is 10–20%; risk of permanent neuronal injury increases with duration. Refractory status epilepticus: seizures continue despite two adequate AED trials. Super-refractory: persists ≥ 24 hours despite anesthesia.

Stepwise Treatment Protocol

11 Epilepsy Syndromes & AED Selection Epilepsy

Key Epilepsy Syndromes

AED Selection by Seizure Type

12 Alzheimer's Disease Neurodegenerative

Alzheimer's disease (AD) is the most common cause of dementia, accounting for 60–70% of cases. Pathologically defined by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (hyperphosphorylated tau protein). These begin accumulating 15–20 years before clinical symptoms. The earliest affected region is the entorhinal cortex/hippocampus, explaining why short-term memory loss is the hallmark presenting symptom.

Clinical progression: Mild cognitive impairment (MCI) due to AD → mild AD (instrumental ADLs affected — finances, medications, cooking) → moderate AD (basic ADLs impaired — dressing, bathing; behavioral symptoms emerge — agitation, delusions, wandering) → severe AD (non-verbal, bed-bound, dysphagia, incontinence). Average survival from diagnosis: 8–10 years.

Diagnosis: Clinical criteria (NIA-AA 2011): insidious onset, progressive amnestic (typical) or non-amnestic (atypical — posterior cortical atrophy/logopenic aphasia) cognitive decline, exclusion of other causes. Biomarkers: CSF (low Aβ42, elevated phospho-tau and total tau), amyloid PET (florbetapir, flutemetamol — positive in AD), tau PET (flortaucipir), and MRI showing medial temporal lobe/hippocampal atrophy disproportionate to age.

Treatment: Cholinesterase inhibitors (mild-moderate): donepezil (Aricept) 5–10 mg daily, rivastigmine (Exelon) patch 4.6–13.3 mg/24hr, galantamine (Razadyne) 8–24 mg daily — modest symptomatic benefit, do not modify disease course. Memantine (Namenda) 10 mg BID (NMDA receptor antagonist) for moderate-severe AD — can be combined with a cholinesterase inhibitor. Anti-amyloid monoclonal antibodies: lecanemab (Leqembi) 10 mg/kg IV biweekly — slowed cognitive decline by 27% over 18 months in the Clarity AD trial; aducanumab (Aduhelm) — controversial accelerated FDA approval; donanemab — targets N-terminal truncated Aβ. Major risk: ARIA (amyloid-related imaging abnormalities) — cerebral edema and/or microhemorrhages, highest in APOE4 homozygotes.

13 Parkinson's Disease Neurodegenerative

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Pathology: loss of dopaminergic neurons in the substantia nigra pars compacta with intraneuronal Lewy bodies (alpha-synuclein aggregates). Symptoms appear when ~60–80% of striatal dopamine is depleted. Mean age of onset: 60 years; prevalence increases with age.

Cardinal Motor Features

The diagnosis requires bradykinesia (slowness and decrement in amplitude/speed of repetitive movements — the core required feature) PLUS at least one of: (1) rest tremor — 4–6 Hz, "pill-rolling," asymmetric at onset, diminishes with action; (2) rigidity — lead-pipe or cogwheel (rigidity + superimposed tremor), present throughout passive range of motion. Postural instability appears later and marks a transition to higher fall risk.

Hoehn & Yahr Staging

Non-Motor Features (Often Precede Motor Symptoms by Years)

REM sleep behavior disorder (RBD — acting out dreams), hyposmia (reduced sense of smell), constipation, depression/anxiety, orthostatic hypotension, urinary urgency, cognitive impairment (PD dementia develops in ~80% over the disease course). RBD + hyposmia + constipation together strongly predict future PD or Lewy body dementia.

Pharmacotherapy

Deep Brain Stimulation (DBS): Bilateral stimulation of the subthalamic nucleus (STN) or globus pallidus interna (GPi) for patients with motor fluctuations refractory to medication optimization. Reduces "off" time by ~60%, reduces dyskinesias (especially GPi), and allows levodopa dose reduction. Patient selection: good levodopa responsiveness (predicts DBS benefit), no significant cognitive impairment or uncontrolled psychiatric disease, adequate surgical fitness.

14 Lewy Body Dementia & Frontotemporal Dementia Neurodegenerative

Dementia with Lewy Bodies (DLB)

Second most common neurodegenerative dementia after AD. Core features (2 of 4 = probable DLB): (1) fluctuating cognition with pronounced variations in attention/alertness, (2) recurrent visual hallucinations (detailed, well-formed — people, animals), (3) REM sleep behavior disorder, (4) spontaneous parkinsonism. The "1-year rule" distinguishes DLB from Parkinson's disease dementia: if dementia develops ≥ 1 year after motor symptoms → PD dementia; if dementia precedes or occurs within 1 year of motor symptoms → DLB. DaTscan (ioflupane SPECT) shows reduced dopamine transporter uptake in the striatum, supporting the diagnosis. Critical management consideration: DLB patients are exquisitely sensitive to neuroleptics — typical antipsychotics (haloperidol) can cause severe, potentially fatal parkinsonism and neuroleptic malignant syndrome. If antipsychotics are needed, use low-dose quetiapine or pimavanserin (Nuplazid — selective 5-HT2A inverse agonist, FDA-approved for PD psychosis).

Frontotemporal Dementia (FTD)

A group of neurodegenerative disorders with predominant frontal and anterior temporal atrophy. Typically younger onset (45–65 years) than AD. Three main clinical variants:

There is no disease-modifying treatment. Management is symptomatic: SSRIs for compulsive behaviors and irritability; trazodone for agitation; no benefit from cholinesterase inhibitors (unlike AD). FTD-ALS overlap: ~15% of FTD patients develop ALS features (C9orf72 hexanucleotide repeat expansion is the most common shared genetic cause).

15 Amyotrophic Lateral Sclerosis (ALS) Neurodegenerative

ALS is the most common motor neuron disease — progressive degeneration of both upper motor neurons (cortex → corticospinal tract) and lower motor neurons (anterior horn cells → peripheral nerves). Incidence: ~2/100,000 per year. Median survival from symptom onset: 3–5 years. Death is usually from respiratory failure. ~10% of cases are familial (SOD1, C9orf72, FUS, TARDBP mutations).

Presentation: Painless, asymmetric limb weakness is the most common onset (~70%) — often distal hand wasting with fasciculations. Bulbar onset (~25%) presents with dysarthria, dysphagia, and tongue fasciculations/atrophy. The hallmark is concurrent UMN signs (hyperreflexia, spasticity, Babinski) and LMN signs (atrophy, fasciculations, weakness) in the same body region — a combination virtually pathognomonic for ALS. Sensation is spared. Eye movements and sphincter function are typically preserved until late stages.

Diagnosis: Primarily clinical, supported by EMG/NCS (widespread active denervation with reinnervation in ≥ 3 body regions; normal sensory conduction). The revised El Escorial criteria require UMN + LMN signs in multiple regions with progressive spread and exclusion of mimics (cervical myelopathy, multifocal motor neuropathy, inclusion body myositis). MRI of brain and spine to exclude structural causes.

Management: Riluzole (Rilutek) 50 mg BID — glutamate antagonist, extends survival by ~2–3 months; the only drug with proven survival benefit until recently. Edaravone (Radicava) — free radical scavenger; slowed functional decline in a subgroup of early ALS patients. Tofersen (Qalsody) — antisense oligonucleotide for SOD1-ALS specifically. Multidisciplinary care: pulmonology (noninvasive ventilation — BiPAP extends survival by months and improves quality of life), nutrition (PEG placement before FVC drops below 50%), speech therapy, PT/OT, palliative care. Discussions about advance directives and tracheostomy/ventilator decisions should occur early.

16 Huntington's Disease Neurodegenerative

Autosomal dominant trinucleotide repeat disorder — CAG expansion in the huntingtin gene (HTT) on chromosome 4. Normal: < 27 CAG repeats; intermediate: 27–35 (premutation); reduced penetrance: 36–39; full penetrance: ≥ 40. The age of onset inversely correlates with repeat length (genetic anticipation — longer repeats in successive generations, especially with paternal inheritance). Usual onset: 30–50 years.

Clinical triad: (1) Chorea — involuntary, irregular, non-repetitive, flowing movements; the most recognized feature; progresses to dystonia and rigidity in later stages. (2) Behavioral/psychiatric symptoms — depression, irritability, apathy, obsessive-compulsive features; often precede motor symptoms by years. (3) Cognitive decline — subcortical pattern (executive dysfunction, psychomotor slowing, impaired attention) progressing to dementia. Juvenile-onset (Westphal variant, ≥ 60 repeats): predominantly rigid-akinetic rather than choreic.

Diagnosis: Genetic testing (CAG repeat count) is definitive. Imaging: caudate nucleus atrophy with ventricular enlargement ("boxcar ventricles") on MRI. Pre-symptomatic genetic testing involves extensive genetic counseling due to psychological and insurance implications. Treatment: Chorea: tetrabenazine (Xenazine) or deutetrabenazine (Austedo) — VMAT2 inhibitors that deplete presynaptic dopamine; can cause depression and suicidality (black box warning). No disease-modifying therapy is available. Median survival: 15–20 years from diagnosis.

17 Multiple Sclerosis Demyelinating

MS is the most common demyelinating disease of the CNS, affecting ~1 million people in the US. It is an autoimmune-mediated inflammatory demyelination of the brain and spinal cord white matter, causing axonal damage and progressive neurological disability. Peak onset: 20–40 years; female:male ratio ~3:1. Prevalence increases with latitude (vitamin D hypothesis).

Clinical Course Subtypes

Common Presentations

Optic neuritis — unilateral painful vision loss (pain with eye movement), central scotoma, APD; most common presenting symptom (~25%). Transverse myelitis — partial (asymmetric) cord syndrome; sensory level, weakness, bowel/bladder dysfunction; MS-related lesions are typically < 2 vertebral segments (vs NMOSD ≥ 3). Internuclear ophthalmoplegia (INO) — bilateral INO in a young patient is highly suggestive of MS. Lhermitte's sign — electric shock sensation down the spine with neck flexion (cervical cord demyelination). Uhthoff's phenomenon — worsening of symptoms with heat/exercise (temperature-dependent conduction block in demyelinated fibers — not a true relapse).

McDonald Criteria (2017 Revision) — Dissemination in Space and Time

MS diagnosis requires demonstration of CNS demyelination disseminated in space (DIS) — lesions in ≥ 2 of 4 typical locations (periventricular, cortical/juxtacortical, infratentorial, spinal cord) — AND disseminated in time (DIT) — simultaneous presence of gadolinium-enhancing and non-enhancing lesions on a single MRI, or a new T2/enhancing lesion on follow-up MRI, or CSF-specific oligoclonal bands (2017 revision allows OCBs to substitute for DIT). This means a single MRI plus positive CSF OCBs can now establish the diagnosis without waiting for a second clinical attack.

Disease-Modifying Therapies (DMTs)

Acute relapse management: IV methylprednisolone 1 g/day for 3–5 days (speeds recovery from relapses but does not change long-term disability). Plasma exchange (PLEX) for steroid-refractory relapses (5–7 exchanges over 10–14 days).

18 Neuromyelitis Optica Spectrum Disorder (NMOSD) Demyelinating

NMOSD is an autoimmune astrocytopathy (not a variant of MS). ~75% of patients are seropositive for aquaporin-4 IgG (AQP4-IgG) antibodies, which target AQP4 water channels on astrocyte foot processes concentrated at the optic nerve, spinal cord, and area postrema. Female predominance (~9:1). More common in Black, Asian, and Hispanic populations compared to MS.

Core clinical syndromes: (1) Optic neuritis — often severe, bilateral, with poor recovery (unlike MS). (2) Longitudinally extensive transverse myelitis (LETM) — ≥ 3 vertebral segments (unlike MS: typically < 2). (3) Area postrema syndrome — intractable nausea, vomiting, hiccups (from dorsal medullary involvement).

Distinguishing NMOSD from MS: NMOSD has AQP4-IgG positivity, long cord lesions, severe optic neuritis, brain MRI often initially normal or with atypical lesions (area postrema, periependymal), CSF typically shows neutrophilic pleocytosis (not lymphocytic) without oligoclonal bands. Treatment: Acute attacks: high-dose IV steroids + PLEX (PLEX is more commonly needed than in MS). Prevention: eculizumab (Soliris — complement C5 inhibitor), inebilizumab (Uplizna — anti-CD19), satralizumab (Enspryng — anti-IL-6R) — all FDA-approved for AQP4+ NMOSD. Rituximab (off-label, anti-CD20) is also widely used. Azathioprine and mycophenolate are alternative options. MS DMTs (interferon-beta, fingolimod, natalizumab) can worsen NMOSD — accurate diagnosis is critical.

19 Guillain-Barré Syndrome Autoimmune

GBS is an acute, immune-mediated polyradiculoneuropathy — the most common cause of acute flaccid paralysis. Incidence: ~1–2/100,000/year. Typically follows an infection by 1–4 weeks (Campylobacter jejuni gastroenteritis is the most common trigger — ~30%; also CMV, EBV, Mycoplasma, Zika, influenza, and post-vaccination). Pathogenesis: molecular mimicry — antibodies against microbial antigens cross-react with gangliosides on peripheral nerve myelin or axons.

Clinical Subtypes

Presentation: Symmetric ascending weakness (legs before arms) over days to 2–4 weeks, areflexia, back/limb pain. Nadir within 4 weeks. Respiratory failure occurs in ~25% (monitor FVC q4–6h: intubate if FVC < 20 mL/kg or decreasing trend, NIF < -30 cmH2O — the "20/30 rule"). Autonomic dysfunction (blood pressure lability, tachycardia, arrhythmias, urinary retention) can be life-threatening.

Diagnosis: CSF: albuminocytologic dissociation (elevated protein with normal WBC) — may be normal in the first week. NCS/EMG: demyelinating pattern (prolonged distal latencies, conduction block, slowed velocities, prolonged F-waves) in AIDP; axonal pattern (reduced CMAP amplitudes with normal velocities) in AMAN. Treatment: IVIG (0.4 g/kg/day × 5 days) or plasma exchange (5 exchanges over 1–2 weeks) — equally effective; combining them adds no benefit. Corticosteroids are NOT effective in GBS (unlike most autoimmune neurological conditions).

20 Myasthenia Gravis Autoimmune

MG is an autoimmune disorder of the neuromuscular junction. ~85% have antibodies against the acetylcholine receptor (AChR) on the postsynaptic membrane; ~5–8% have anti-MuSK (muscle-specific kinase) antibodies; ~5–10% are "seronegative" (may have anti-LRP4 or low-titer AChR). Bimodal age distribution: women 20–30, men 60–70. Strong association with thymic abnormalities: 65% thymic hyperplasia, 10–15% thymoma.

Presentation: Fluctuating, fatigable weakness — worse with use, better with rest. Ocular MG (~50% at onset): ptosis (often asymmetric) and diplopia. Generalized MG: spreads to bulbar (dysphagia, dysarthria, facial weakness), limb (proximal > distal), and respiratory muscles. Myasthenic crisis: respiratory failure from weakness (FVC < 15–20 mL/kg); triggers include infection, surgery, medication changes, or initiation of corticosteroids ("steroid dip"). Anti-MuSK MG has a distinct phenotype: more prominent facial, bulbar, and respiratory weakness; less ocular involvement; poor response to cholinesterase inhibitors.

Diagnosis: AChR antibodies (positive in 85% of generalized, 50% of pure ocular). Ice test (place ice pack on ptotic eyelid for 2 minutes — improvement suggests MG; cooling improves NMJ function). Edrophonium (Tensilon) test — rarely used now due to cardiac risks. Repetitive nerve stimulation: decrement of ≥ 10% in CMAP amplitude at 3 Hz (low-frequency stimulation). Single-fiber EMG: increased jitter — most sensitive test for MG (~95%).

Treatment: Pyridostigmine (Mestinon) 60 mg PO TID (acetylcholinesterase inhibitor — symptomatic). Immunosuppression: prednisone (start low, titrate up — watch for initial worsening), steroid-sparing agents (azathioprine, mycophenolate, tacrolimus). Thymectomy — for all thymoma patients; also beneficial in AChR+ generalized MG even without thymoma (MGTX trial). Crisis management: IVIG or PLEX for rapid improvement. Efgartigimod (Vyvgart) — FcRn inhibitor that reduces IgG levels; FDA-approved for generalized MG. Avoid in MG: aminoglycosides, fluoroquinolones, macrolides, magnesium, beta-blockers, neuromuscular blocking agents, D-penicillamine, IV contrast (relative), botulinum toxin.

21 Autoimmune Encephalitis Autoimmune

A group of inflammatory brain diseases caused by antibodies against neuronal surface or intracellular antigens. The most common and treatable form is anti-NMDA receptor encephalitis — the most frequent cause of autoimmune encephalitis, predominantly affecting young women. Associated with ovarian teratoma in ~50% of female patients > 18 years.

Anti-NMDA receptor encephalitis progression: (1) Prodromal viral-like illness → (2) Psychiatric symptoms (psychosis, agitation, hallucinations — often initially misdiagnosed) → (3) Seizures → (4) Movement disorders (orofacial dyskinesias, choreoathetosis) → (5) Autonomic instability (dysautonomia, hypoventilation) → (6) Decreased consciousness (often requiring ICU care). Other antibody-associated syndromes: Anti-LGI1: faciobrachial dystonic seizures, hyponatremia (SIADH); Anti-CASPR2: limbic encephalitis, neuromyotonia, Morvan syndrome; Anti-AMPAR: limbic encephalitis, high tumor association; Anti-GABA-B: limbic encephalitis, seizures, SCLC association.

Diagnosis: CSF antibody testing (send both CSF and serum); CSF may show lymphocytic pleocytosis and/or oligoclonal bands. MRI may be normal or show medial temporal FLAIR signal. EEG often shows diffuse slowing or extreme delta brush pattern (specific for anti-NMDA receptor encephalitis). Treatment: First-line: IV methylprednisolone + IVIG or PLEX. Second-line (if poor response after 2 weeks): rituximab + cyclophosphamide. Tumor removal (teratoma resection) is critical — recovery depends on it. Relapse rate ~12–25% (higher without tumor removal or without adequate immunotherapy).

22 Essential Tremor Movement

Essential tremor (ET) is the most common movement disorder — 8–10 times more common than Parkinson's disease. Bilateral, largely symmetric action tremor (postural and kinetic) at 4–12 Hz, predominantly affecting the hands and arms; may also involve the head ("yes-yes" or "no-no"), voice, and legs. Typically worsens with age. A family history is present in ~50% (autosomal dominant with variable penetrance). Alcohol transiently improves tremor in ~50–70% of patients — a useful historical clue.

ET vs PD tremor: ET is primarily an action/postural tremor (holding arms outstretched, pouring water); PD tremor is primarily at rest (pill-rolling). ET is usually bilateral and symmetric at onset; PD is asymmetric. ET lacks the bradykinesia and rigidity seen in PD. ET may involve head tremor; PD head tremor is rare without limb involvement. However, ~5% of ET patients later develop PD.

Treatment: First-line: propranolol (60–320 mg/day — long-acting preferred) or primidone (25–750 mg at bedtime — start low, metabolized to phenobarbital). Second-line: topiramate, gabapentin, alprazolam. Botulinum toxin injections for head/voice tremor refractory to oral medications. DBS of the ventral intermediate nucleus (VIM) of the thalamus or MRI-guided focused ultrasound thalamotomy for severe, medication-refractory ET.

23 Dystonia Movement

Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal postures and/or repetitive movements. Classified by: (1) body distribution: focal (one region — cervical dystonia, blepharospasm, writer's cramp), segmental (two or more contiguous regions), multifocal (two or more non-contiguous), generalized, hemidystonia (one side — suggests contralateral basal ganglia lesion); (2) age of onset: early (< 26, often generalized, DYT1 gene) vs adult (usually focal). Cervical dystonia (torticollis) is the most common focal dystonia.

Treatment: Focal dystonias: botulinum toxin (onabotulinumtoxinA = Botox, abobotulinumtoxinA = Dysport, incobotulinumtoxinA = Xeomin) injected into affected muscles — first-line and most effective treatment. Generalized dystonia: anticholinergics (trihexyphenidyl — tolerated better in children than adults), baclofen, benzodiazepines. DBS of the GPi for medication-refractory generalized dystonia (especially DYT1-positive — ~60% improvement). Dopa-responsive dystonia (DRD / Segawa disease) — presents in childhood with diurnal fluctuation (worse in evening); dramatic and sustained response to low-dose levodopa; caused by GTP cyclohydrolase 1 deficiency. Always try levodopa in childhood-onset dystonia.

24 Chorea, Tics & Tourette's Movement

Chorea

Involuntary, irregular, purposeless, non-rhythmic movements that flow from one body part to another. Key causes: Huntington's disease (see Section 16), Sydenham's chorea (post-streptococcal, associated with rheumatic fever — "St. Vitus' dance"), chorea gravidarum (pregnancy — often in patients with prior Sydenham's or antiphospholipid syndrome), drug-induced (levodopa, oral contraceptives, phenytoin, stimulants), vascular (subthalamic or caudate stroke), autoimmune (anti-basal ganglia antibodies, SLE). When chorea affects one side: hemiballismus — large-amplitude, flinging, proximal limb movements, classically from a contralateral subthalamic nucleus lesion (often small lacunar infarct in a diabetic patient).

Tics & Tourette Syndrome

Tics are sudden, rapid, recurrent, non-rhythmic motor movements or vocalizations. They are semi-voluntary — preceded by a premonitory urge and temporarily suppressible (unlike chorea). Tourette syndrome requires: onset before age 18; multiple motor tics + ≥ 1 vocal tic (not necessarily concurrent); tics present for > 1 year. Peak tic severity: ages 10–12; ~2/3 of patients improve significantly by adulthood. Common comorbidities: ADHD (~50%), OCD (~30%), anxiety, learning disabilities. Coprolalia (involuntary obscene utterances) occurs in < 15% of Tourette's patients — it is not required for diagnosis and is far less common than popularly believed.

Treatment: Education and watchful waiting if tics are mild. Behavioral therapy: Comprehensive Behavioral Intervention for Tics (CBIT) — first-line non-pharmacological. Medications (for moderate-severe functional impairment): alpha-2 agonists (clonidine, guanfacine — first-line pharmacological; also help ADHD comorbidity), VMAT2 inhibitors (tetrabenazine, deutetrabenazine), antipsychotics (fluphenazine, aripiprazole — effective but risk of tardive dyskinesia with prolonged use). DBS of the GPi for severe, refractory cases.

25 Drug-Induced Movement Disorders Movement

26 Migraine Headache

Migraine is the second most common primary headache (after tension-type) but the most disabling — affects ~15% of the global population; female:male ratio ~3:1. Migraine is a neurovascular disorder involving cortical spreading depression, trigeminal activation, and neurogenic inflammation of meningeal vessels — not merely a "vascular headache."

Diagnostic Criteria (ICHD-3)

Migraine without aura: ≥ 5 attacks lasting 4–72 hours (untreated) with at least 2 of: unilateral, pulsating, moderate-severe intensity, aggravation by routine physical activity; PLUS at least 1 of: nausea/vomiting, photophobia + phonophobia. Migraine with aura: ≥ 2 attacks with fully reversible visual (most common — scintillating scotoma, zigzag lines), sensory (tingling), or language symptoms; aura develops over ≥ 5 minutes, each symptom lasts 5–60 minutes, followed by headache within 60 minutes.

Acute Treatment

Preventive Therapy (Indicated When ≥ 4 Migraine Days/Month)

27 Tension-Type & Cluster Headache Headache

Tension-Type Headache (TTH)

The most common primary headache. Bilateral, pressing/tightening ("band-like") quality, mild-to-moderate intensity, not aggravated by routine physical activity. No nausea/vomiting (mild nausea allowed in chronic TTH). May have photophobia OR phonophobia but not both. Episodic (< 15 days/month) vs chronic (≥ 15 days/month for ≥ 3 months). Treatment: acute — OTC analgesics (acetaminophen 1000 mg, ibuprofen 400 mg); preventive (for chronic TTH) — amitriptyline 10–75 mg QHS (best evidence).

Cluster Headache

The most severe of all primary headaches — sometimes called "suicide headache." Strictly unilateral, orbital/supraorbital/temporal, excruciating pain lasting 15–180 minutes per attack, occurring 1–8 times daily in clusters lasting weeks to months, separated by remission periods of months to years (episodic form). Chronic form: no remission > 3 months. Male predominance (~3:1). Always accompanied by ipsilateral cranial autonomic symptoms: lacrimation, conjunctival injection, nasal congestion/rhinorrhea, ptosis, miosis, periorbital edema, forehead sweating. Patients are restless/agitated during attacks (unlike migraine patients who prefer to lie still in a dark room).

Acute treatment: (1) High-flow oxygen 12–15 L/min via non-rebreather mask for 15 minutes — effective in ~70%; (2) Sumatriptan 6 mg SC (fastest onset) or 20 mg intranasal — response within 10–15 minutes. Prevention: Verapamil (first-line, 240–960 mg/day in divided doses — ECG monitoring required for PR prolongation); short-term bridging with prednisone taper (60 mg × 5 days, then taper over 2–3 weeks) or greater occipital nerve block (GON block — lidocaine/bupivacaine ± steroid). Lithium, galcanezumab (FDA-approved for episodic cluster headache), topiramate are alternative preventives.

28 Secondary Headache Red Flags & Medication Overuse Headache Headache

"SNOOP" Red Flags for Secondary Headache

Medication Overuse Headache (MOH)

Headache occurring ≥ 15 days/month developing as a consequence of regular overuse of acute headache medications for > 3 months. Thresholds: simple analgesics ≥ 15 days/month; triptans, ergots, opioids, or combination analgesics ≥ 10 days/month. MOH is the third most common headache disorder globally. Treatment: withdrawal of the overused medication (abrupt for triptans/ergots; may taper opioids/barbiturates), bridging therapy (naproxen 500 mg BID, corticosteroid taper, or nerve block), and initiation/optimization of preventive therapy. Preventive CGRP monoclonal antibodies have shown efficacy even without withdrawal — a paradigm shift.

29 Peripheral Neuropathy Neuromuscular

Peripheral neuropathy is damage to the peripheral nerves causing weakness, sensory loss, and/or autonomic dysfunction. The most common type is distal symmetric polyneuropathy (DSPN), presenting with stocking-glove numbness and tingling, with the feet affected first (longest axons are most vulnerable — "length-dependent"). The most common cause worldwide is diabetic neuropathy, affecting ~50% of diabetics over their lifetime.

Etiologic Classification

Workup: Labs: fasting glucose/A1c, CBC, CMP, B12, TSH, SPEP with immunofixation, ESR/CRP. If those are unrevealing: HIV, RPR, ANA, anti-Ro/La, paraneoplastic panel, heavy metals. EMG/NCS distinguishes axonal (reduced amplitudes, normal velocities) from demyelinating (slow velocities, prolonged distal latencies, conduction block). Skin biopsy (intraepidermal nerve fiber density) for small fiber neuropathy (burning pain, autonomic symptoms, normal NCS — standard NCS only tests large fibers).

Neuropathic pain treatment: First-line: duloxetine (Cymbalta) 60 mg/day, pregabalin (Lyrica) 150–300 mg/day, gabapentin (Neurontin) 300–3600 mg/day. Second-line: TCAs (amitriptyline, nortriptyline), topical capsaicin 8% patch, lidocaine 5% patch. Avoid opioids as first-line; consider tramadol only for short-term rescue.

30 Myopathies Neuromuscular

Myopathies present with proximal, symmetric weakness (difficulty rising from chairs, climbing stairs, overhead reaching) without sensory loss. Key distinguishing features from neuropathy: proximal > distal weakness, no fasciculations, normal or reduced reflexes (not absent unless severe), elevated CK.

Inflammatory Myopathies

Other Myopathies

Statin myopathy: Most common drug-induced myopathy. Spectrum: myalgia (most common) → myopathy (CK elevated) → rhabdomyolysis (rare). CK should be checked if symptomatic. If CK > 10× ULN, discontinue statin. Hypothyroid myopathy: Proximal weakness, myalgia, elevated CK, delayed relaxation of reflexes; resolves with thyroid replacement. Steroid myopathy: Proximal weakness, atrophy, normal CK (unlike inflammatory myopathies); risk increases with fluorinated corticosteroids (dexamethasone > prednisone).

31 Nerve Entrapment Syndromes Neuromuscular

32 Meningitis Infection

Inflammation of the meninges. The classic triad — headache, fever, neck stiffness — is present in only ~45% of bacterial meningitis cases; however, almost all have at least two of four signs: headache, fever, nuchal rigidity, altered mental status. Kernig's sign (resistance/pain on knee extension with hip flexed to 90°) and Brudzinski's sign (involuntary hip flexion when the neck is passively flexed) have high specificity but low sensitivity (~5%).

CSF Profiles by Etiology

*Early viral meningitis (< 24h) may show neutrophilic predominance before shifting to lymphocytes.

Empiric Treatment — Bacterial Meningitis

Dexamethasone 0.15 mg/kg IV q6h × 4 days — give BEFORE or WITH first dose of antibiotics. Proven benefit in pneumococcal meningitis (reduces mortality and hearing loss). Do NOT delay antibiotics for LP — if LP will be delayed, draw blood cultures and start empiric antibiotics + dexamethasone immediately, then LP when feasible.

33 Encephalitis & Brain Abscess Infection

Viral Encephalitis

Herpes simplex encephalitis (HSE) is the most common sporadic fatal encephalitis and a neurological emergency. HSV-1 accounts for ~95% of cases (via reactivation in the trigeminal ganglion with retrograde spread to the temporal lobe). Classic presentation: acute fever + altered mental status + focal temporal lobe signs (personality change, olfactory/gustatory hallucinations, aphasia, seizures). MRI shows T2/FLAIR hyperintensity in the medial temporal lobes and insular cortex (often asymmetric). CSF: lymphocytic pleocytosis, elevated protein, normal glucose, HSV PCR positive (sensitivity ~95%). Treatment: acyclovir 10 mg/kg IV q8h for 14–21 days — do NOT wait for PCR results. Untreated mortality is ~70%; with acyclovir, ~20%. Delayed treatment worsens outcomes.

Other viral encephalitides: arboviruses (West Nile, Eastern equine, St. Louis — look for summer/fall, mosquito exposure), CMV (immunocompromised — ventriculitis pattern), VZV, EBV. West Nile: only ~1% of infections cause neuroinvasive disease (encephalitis, meningitis, or acute flaccid paralysis); asymmetric flaccid paralysis mimicking poliomyelitis is characteristic.

Brain Abscess

Encapsulated collection of pus within the brain parenchyma. Sources: contiguous spread (sinusitis → frontal lobe, otitis/mastoiditis → temporal lobe/cerebellum), hematogenous (endocarditis, dental infections, pulmonary AVMs in hereditary hemorrhagic telangiectasia — HHT), post-neurosurgical, penetrating trauma. Most common organisms: mixed aerobic/anaerobic; Streptococci (~70%), Bacteroides, Staphylococci. Immunocompromised: Toxoplasma (HIV + ring-enhancing lesions), Nocardia, Aspergillus.

Presentation: Headache (most common — 70%), focal deficits, fever (only ~50%), seizures. Triad of headache + fever + focal deficit is present in < 50%. Diagnosis: Contrast MRI: ring-enhancing lesion with restricted diffusion on DWI (bright on DWI, dark on ADC — this distinguishes abscess from tumor necrosis/cystic tumor, which typically shows facilitated diffusion). Treatment: Empiric antibiotics: ceftriaxone + metronidazole ± vancomycin (for post-surgical). Aspiration for abscess > 2.5 cm or mass effect. Excision if encapsulated and accessible or no response to aspiration + antibiotics. Duration: 6–8 weeks IV antibiotics.

34 Prion Disease Infection

Prion diseases (transmissible spongiform encephalopathies) are invariably fatal neurodegenerative disorders caused by misfolded prion protein (PrPSc). Creutzfeldt-Jakob disease (CJD) is the most common. Subtypes: sporadic (sCJD — ~85%, mean age 65, no identifiable cause), familial (fCJD — ~10–15%, PRNP gene mutations), iatrogenic (contaminated surgical instruments, dura mater grafts, cadaveric growth hormone), variant CJD (vCJD — acquired from bovine spongiform encephalopathy/"mad cow disease," younger patients, psychiatric onset, later neurological decline).

sCJD presentation: Rapidly progressive dementia (weeks to months — NOT months to years like Alzheimer's) with myoclonus ("startle myoclonus"), ataxia, visual symptoms, pyramidal/extrapyramidal signs, akinetic mutism in late stage. Median survival: 5 months from symptom onset. Diagnosis: MRI: cortical ribboning (DWI/FLAIR high signal along the cortical surface) and/or caudate/putamen signal abnormality — highly sensitive (~92%). EEG: periodic sharp wave complexes (PSWCs) at ~1 Hz — present in ~65% but late finding. CSF: RT-QuIC (real-time quaking-induced conversion) assay — sensitivity ~92%, specificity ~99%; elevated 14-3-3 protein (less specific), elevated total tau. Definitive diagnosis requires brain biopsy/autopsy. There is no treatment — care is palliative.

35 Normal Pressure Hydrocephalus Special

NPH is a communicating hydrocephalus (ventricular enlargement without obstruction) presenting with the classic triad: "wet, wacky, and wobbly" — (1) gait disturbance (magnetic/apraxic gait — feet appear glued to the floor, wide-based, short shuffling steps), (2) urinary incontinence (urgency progressing to incontinence), (3) dementia (subcortical pattern — psychomotor slowing, apathy, inattention, executive dysfunction). Gait is typically the earliest and most responsive to treatment. NPH is one of the few reversible causes of dementia.

Diagnosis: MRI: ventriculomegaly out of proportion to sulcal enlargement (Evans' index = frontal horn width / biparietal diameter > 0.3); callosal angle < 90° on coronal sections; periventricular T2 hyperintensity (transependymal CSF flow). Large volume LP (removal of 30–50 mL CSF) — assess gait before and 1–4 hours after; improvement supports diagnosis and predicts shunt response. Continuous lumbar drainage over 72 hours is even more sensitive. Treatment: Ventriculoperitoneal (VP) shunt — improvement in gait (>70%), continence (~50%), cognition (~40%). Programmable shunts allow non-invasive pressure adjustments. Complications: subdural hematoma, infection, shunt malfunction.

36 Idiopathic Intracranial Hypertension Special

Also called pseudotumor cerebri. Elevated intracranial pressure without hydrocephalus or mass lesion. Classic patient: overweight woman of childbearing age. Risk factors: obesity, weight gain, vitamin A excess/retinoids, tetracyclines (doxycycline, minocycline), growth hormone, oral contraceptives (debated).

Presentation: Headache (most common — daily, worse with Valsalva/positional, may be pulsatile), transient visual obscurations (brief graying/blacking out of vision lasting seconds, often with positional change), papilledema (bilateral disc edema on fundoscopy — the hallmark finding), CN VI palsy (false localizing sign from elevated ICP), pulsatile tinnitus ("whooshing" synchronous with heartbeat).

Diagnostic criteria (modified Dandy): (1) Symptoms/signs of raised ICP (papilledema, headache, visual symptoms); (2) LP opening pressure ≥ 25 cmH2O (in lateral decubitus, legs relaxed); (3) Normal CSF composition; (4) No mass, hydrocephalus, or venous sinus thrombosis on imaging (MRI/MRV). Treatment: Weight loss (~5–10% weight loss can resolve the condition). Acetazolamide (Diamox) 500 mg BID, titrate to 1–2 g/day (carbonic anhydrase inhibitor — reduces CSF production; the IIHTT trial confirmed benefit for visual function). Topiramate (secondary — also causes weight loss + reduces CSF production). If vision threatened: optic nerve sheath fenestration or VP/lumboperitoneal shunt. Venous sinus stenting for patients with venous sinus stenosis and pressure gradient.

37 Narcolepsy & Restless Legs Syndrome Special

Narcolepsy

Narcolepsy type 1 (with cataplexy) is caused by autoimmune-mediated destruction of hypocretin/orexin-producing neurons in the lateral hypothalamus, resulting in undetectable CSF hypocretin-1 levels (< 110 pg/mL). Strongly associated with HLA-DQB1*06:02 (present in ~98% of type 1 narcolepsy). Narcolepsy type 2: excessive daytime sleepiness without cataplexy; normal CSF hypocretin.

Pentad of narcolepsy type 1: (1) Excessive daytime sleepiness (the primary and constant symptom — irresistible "sleep attacks"), (2) cataplexy (sudden loss of muscle tone triggered by strong emotions — laughing, surprise — pathognomonic for type 1), (3) sleep paralysis, (4) hypnagogic/hypnopompic hallucinations, (5) disrupted nocturnal sleep. Diagnosis: Overnight polysomnography (to exclude other sleep disorders) followed by multiple sleep latency test (MSLT): mean sleep latency ≤ 8 minutes with ≥ 2 sleep-onset REM periods (SOREMPs). Treatment: Sleepiness: modafinil 100–400 mg/day (first-line), armodafinil, solriamfetol, or traditional stimulants (methylphenidate, dextroamphetamine). Cataplexy: sodium oxybate (Xyrem/Xywav — also improves all symptoms; taken at bedtime + again 2.5–4 hours later), SNRIs (venlafaxine), TCAs (clomipramine), pitolisant (H3 receptor antagonist/inverse agonist).

Restless Legs Syndrome (RLS) / Willis-Ekbom Disease

An urge to move the legs, usually accompanied by uncomfortable sensations (creeping, crawling, aching, tingling), (1) worse at rest, (2) relieved by movement, (3) worse in the evening/night. Affects ~5–10% of adults. Associated with iron deficiency (check ferritin — treat if < 75 ng/mL even if in "normal" range), CKD/dialysis, pregnancy, neuropathy, and dopaminergic medications.

Treatment: Address iron deficiency (oral iron with vitamin C, or IV iron if oral fails or ferritin < 30). Intermittent RLS: low-dose dopamine agonist PRN or gabapentinoid. Chronic moderate-severe: alpha-2-delta ligands (gabapentin enacarbil 600 mg, pregabalin 150–300 mg — preferred first-line to avoid augmentation). Dopamine agonists (pramipexole, ropinirole, rotigotine patch) — effective but risk of augmentation (paradoxical worsening with earlier onset, increased intensity, spread to other body parts with chronic use — occurs in 40–60% within 10 years). Low-dose opioids (oxycodone, methadone) for refractory cases.

38 Neurosarcoidosis Special

Neurological involvement occurs in ~5–10% of sarcoidosis patients but can be the presenting manifestation in ~50% of those affected. Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Neurosarcoidosis can affect any part of the nervous system.

Most common presentations: (1) Cranial neuropathy (~55%) — CN VII (facial palsy, most common; bilateral facial palsy = think sarcoidosis, Lyme, GBS), CN II (optic neuropathy). (2) Leptomeningeal enhancement on MRI (basal predominant). (3) Hypothalamic-pituitary dysfunction (DI, hyperprolactinemia, panhypopituitarism). (4) Myelopathy (longitudinally extensive, can mimic NMOSD). (5) Peripheral neuropathy (small fiber most common). (6) Myopathy (chronic, nodular).

Diagnosis: Biopsy is the gold standard (non-caseating granulomas). CSF: lymphocytic pleocytosis, elevated protein, low glucose (in ~20%), elevated ACE (low sensitivity ~50%). Serum ACE elevated in ~60% (low specificity). Chest imaging (hilar lymphadenopathy in ~90% of sarcoidosis). FDG-PET may identify biopsy-accessible sites. Soluble IL-2 receptor and lysozyme may support diagnosis. Treatment: Corticosteroids (prednisone 0.5–1 mg/kg/day) — first-line; steroid-sparing agents for chronic disease: methotrexate, mycophenolate, azathioprine. Infliximab (anti-TNF-alpha) for refractory neurosarcoidosis — strong evidence. Cyclophosphamide for severe, refractory cases.

39 Lumbar Puncture & CSF Analysis

Indications: Suspected meningitis/encephalitis, SAH (if CT negative), MS workup, NPH evaluation, IIH diagnosis, carcinomatous meningitis, Guillain-Barré. Contraindications: Increased ICP with mass lesion (risk of herniation — get CT first), coagulopathy (INR > 1.5, platelets < 50K), skin infection at puncture site.

Technique: Patient in lateral decubitus or sitting position. Identify L3-L4 or L4-L5 interspace (the spinal cord ends at L1-L2 in adults). Use aseptic technique; insert spinal needle (20 or 22 gauge) with bevel parallel to the longitudinal dural fibers. Measure opening pressure (normal: 6–25 cmH2O in lateral decubitus with legs relaxed). Collect CSF in 4 tubes: (1) cell count + differential, (2) protein + glucose, (3) Gram stain, culture, (4) special studies (cytology, PCR, OCBs, biomarkers).

Normal CSF Values

Post-LP headache: Occurs in ~10–30% — worse upright, relieved lying flat (low-pressure headache from CSF leak at the puncture site). Risk reduced by using atraumatic (Sprotte/Whitacre) needles. Treatment: bed rest, hydration, caffeine (300 mg PO), and autologous epidural blood patch (10–20 mL of patient's blood injected into epidural space — ~90% effective for persistent symptoms).

40 EEG Interpretation

Electroencephalography records cortical electrical activity via scalp electrodes (standard 10-20 system with 21 electrodes). Normal adult background: alpha rhythm (8–13 Hz) predominant over the posterior regions, attenuates with eye opening. Slower rhythms: theta (4–7 Hz) and delta (< 4 Hz) are normal during drowsiness and sleep but abnormal if persistent during wakefulness.

Key EEG Patterns

41 EMG / Nerve Conduction Studies

EMG/NCS is the electrodiagnostic study of the peripheral nervous system — the most important test for distinguishing neuropathy from myopathy and for localizing peripheral nerve lesions.

Nerve Conduction Studies (NCS)

Electrically stimulate a peripheral nerve and record the response. Motor NCS: stimulate nerve, record from muscle — generates compound muscle action potential (CMAP). Measures: distal latency, conduction velocity, CMAP amplitude, F-wave latency. Sensory NCS: stimulate and record from the nerve itself — generates sensory nerve action potential (SNAP). Key patterns:

Electromyography (Needle EMG)

A concentric needle electrode is inserted into muscles to record electrical activity. Three phases of assessment: (1) Insertional activity — brief burst from needle insertion; increased in denervation, decreased in fibrosis/end-stage. (2) Spontaneous activity at rest — normal muscle is electrically silent; fibrillations + positive sharp waves = active denervation; fasciculations = LMN pathology; myotonic discharges = myotonic dystrophy or myotonia. (3) Motor unit action potentials (MUAPs) during voluntary contraction — neuropathic pattern: large, polyphasic, long-duration MUAPs with reduced recruitment (surviving motor units grow larger via reinnervation); myopathic pattern: small, short-duration, polyphasic MUAPs with early recruitment (many weak motor units firing to compensate).

42 Neuroimaging — CT, MRI, MRA & Sequences

CT Applications

MRI Sequences

43 Classification Systems (All)

44 Medications Master Table Meds

Antiepileptic Drugs (AEDs)

MS Disease-Modifying Therapies

See Section 17 table for complete MS DMT listing with route, mechanism, efficacy, and key risks.

Parkinson's Disease Drugs

See Section 13 table for complete PD pharmacotherapy with mechanisms, roles, and pearls.

Migraine Medications

See Section 26 tables for acute treatment and preventive therapy.

Stroke Medications

Other Neurological Medications

45 Abbreviations Master List

Anatomy

Diagnoses

Procedures & Diagnostics

Medications & Labs

Other / General

46 Risk Scores & Screening Tools