Neurology Of Systemic DX

Brain adaptation principles: Hypo-osmolality[…]: rapidly (hours) cellular loss of Na/K/Cl + water; slowly (days) loss of osmolytes (glutamate, glutamine, taurine, myo-inositol); Hyper-osmolality[…]: rapid Na+ accumulation from CSF/plasma/extracellular fluid.

General rule: K disturbances affect PNS[…]; Na affects CNS[…].

Calcium: ~50% bound by albumin[…] — correct for albumin or get ionized fraction.

Magnesium: at NMJ, Mg competes with Ca → affects ACh release[…] + muscle excitability.

Common causes: thiazide diuretics, fluid overload, SSRIs/SNRIs (venlafaxine), oxcarbazepine/carbamazepine/valproate, cerebral salt wasting[…].

Clinical thresholds: Often asymptomatic when Na >125; Progressively impaired responsiveness when Na <120-125; Rapid decrease >20 mmol/L[…] from baseline → seizures.

Treatment (correct slowly to avoid osmotic demyelination[…]): 2024 guidelines: Na <120 → avoid correction >10 mmol/L in 24h or >18 mmol/L in 48h[…]; Na <105 or additional risk factors (alcohol use disorder, hypokalemia, malnutrition, liver disease): >8 mmol/L/day is excessive; Correction rate: increase ~1 mmol/L/hr using 3% NaCl (513 mmol/L)[…].

Osmotic Demyelination Syndrome (ODS) / Central Pontine Myelinolysis (CPM): Symptoms: supranuclear bulbar dysfunction[…] (facial weakness, dysarthria, dysphagia) + tetraparesis → may progress to locked-in[…] syndrome; MRI: symmetric T2 hyperintensity in central basis pontis[…]; shape may be trident or bat-shaped[…] from preferential horizontal tract involvement, sparing vertical tracts; Classically occurs after correction of severe hyponatremia with hypertonic saline.

Extrapontine myelinolysis: subcortical white matter + deep gray matter; impairment of consciousness + corticobulbar signs + parkinsonian[…] picture with dysarthria/dysphagia.

Hypernatremia: free water deficit, central diabetes insipidus.: Severe >160 mmol/L; patients often unresponsive; GTC seizures uncommon even at high levels; Correction rate: reduce 1-2 mmol/L/hr → moderate hypernatremia (150-155); avoid aggressive normal correction (risk of hyponatremia from secondary effects); DI with Na >150: IV desmopressin[…] + 0.45% NaCl or 5% dextrose.

Hypokalemia: K <2 mmol/L → reduced muscle excitability → proximal leg/neck/trunk weakness; rarely ascending mimicking GBS[…] but without sensory changes, areflexia, or CN deficits.

EKG: U waves and ST depression[…]. Hyperkalemia (renal/adrenal failure): K >7 → peaked T waves + short QT + prolonged PR + wide QRS.

Weakness → quadriplegia + respiratory failure + myotonia[…].

Hypophosphatemia: severe (<0.5-1.0 mg/dL): diaphragmatic weakness[…] → can't wean from ventilator (phosphate repletion improves inspiratory pressures); rarely rapidly progressive quadriplegia + ptosis + dysphagia. Hypocalcemia: severe (<3 mg/dL): paresthesias → cramps → hand/foot spasms → laryngeal stridor.

Chvostek[…] sign (tap facial nerve → ipsilateral twitching).

Trousseau[…] sign (BP cuff → carpopedal spasm with finger flexion + thumb adduction). Hypercalcemia (primary hyperparathyroidism, cancer): severe (>14 mg/dL) → lethargy/confusion/coma.

Treatment: volume expansion + calcitonin[…] + loop diuretics. Hypomagnesemia (<1.7): muscle twitching, myoclonus, startle responses, postural tremor; +Trousseau/Chvostek; seizures if severe.

Mild hypermagnesemia can unmask MG[…]. Hypermagnesemia: usually iatrogenic (e.g., eclampsia tx). Decreased/absent muscle stretch reflexes + rapidly progressive limb weakness + bifacial weakness + bulbar weakness.

Uremic encephalopathy: Manifestations: lassitude/torpor + distractibility/inattention + frequent yawning + multifocal myoclonus + asterixis[…] + action/postural tremor; Occurs when GFR <15 or inadequate dialysis; Asterixis[…] is loss of posture (not a tremor despite "flapping tremor" name); MRI: generally normal; look for SDH (thrombocytopenia) and PRES[…] (HTN); EEG: nonspecific delta, semirhythmic slow wave bursts + triphasic waves; DDX: PRES vs medication toxicity (especially cefepime[…] in renal failure → NCSE), SDH, anoxic-ischemic injury; Treatment: HD (low flow rates, shorter time, smaller membranes, limit plasma osmolality changes).

Dialysis disequilibrium syndrome: Symptoms: HA/confusion → seizures/coma DURING[…] hemodialysis (most commonly first session, end of procedure); Mechanism: reverse urea effect[…] — urea clears more slowly from CSF than blood → osmotic gradient → cerebral vasodilation + edema; Diagnosis of exclusion (first consider PRES, drug toxicity, SDH). PNS complications of renal failure: Chronic renal failure polyneuropathy: length-dependent sensorimotor; axonal loss + demyelination from toxins. Acute motor polyneuropathy: mimics GBS without ophthalmoplegia/severe dysautonomia/need for mech vent.

Ischemic monomelic neuropathy[…]: acute mononeuropathy after AV fistula placement for HD → sudden diversion of blood supply affecting median/ulnar/radial nerves.

Treatment: urgent fistula revision[…].

Acute liver failure: liver dysfunction + encephalopathy + coagulopathy (INR >1.5) within 26 weeks[…] of liver disease onset.

Causes: viral, iatrogenic/toxic, Wilson disease, autoimmune hepatitis, pregnancy-associated (HELLP), ischemic hepatitis ("shock liver"), Budd-Chiari[…].

Pathophys: rapid rise of ammonia and glutamine[…] → osmotic + cytotoxic edema + cerebrovascular vasodilation → cerebral edema. Risk factors: sepsis/SIRS, higher-grade encephalopathy, NH3 >100, renal failure. West Haven grading: Grade 1: impaired awareness, sleep cycles. EEG: increased theta. Grade 2: lethargy, asterixis. EEG: increased theta. Grade 3: somnolence.

EEG: disorganization + triphasic GPDs[…]. Grade 4: coma. EEG: diffuse suppression. Treatment: Manage at center with liver transplant capability.

CRRT[…] at West Haven grades 2-4 to lower NH3 even without acute renal injury (safer/more effective than lactulose for acute HE).

ICP management: hypertonic saline > mannitol[…] (mannitol has higher renal failure rates + rebound ICP increases).

ASMs: prophylactic ASM not indicated; if seizures → keppra or vimpat[…] (IV, not hepatically metabolized). AVOID phenytoin, carbamazepine, valproate. Induced hypothermia does NOT improve survival.

Chronic hepatic encephalopathy: Causes: hepatitis B/C, alcohol, NAFLD, Wilson, hemochromatosis, autoimmune hepatitis; Pathophys: portosystemic shunting[…] + inflammation + hyperammonemia → BBB permeability; Symptoms: dysexecutive syndrome + apraxia + sleep-wake inversion + personality changes; Treatment: maintain Na >130, minimize PPI use (bacterial overgrowth → HE risk), 1st line lactulose[…] (continue after 1st episode to prevent recurrence), 2nd line add rifaximin[…], 3rd line endovascular obliteration, 4th line liver transplant.

Acquired hepatocellular degeneration: Progressive non-fluctuating[…] (unlike HE) with neuropsychiatric + movement disorders (tremor, dystonia, oral dyskinesias, parkinsonism, cerebellar dysfunction); Does NOT improve with ammonia-lowering therapies; Pathophys: manganese deposition[…] in basal ganglia from portosystemic shunting; MRI: symmetric T1 hyperintensities[…] in globus pallidus; EPS generally do NOT respond to dopaminergic therapies.

Hepatic myelopathy: progressive spastic paraparesis[…] without sensory or sphincter dysfunction. Pathophys: toxic injury to bilateral CST from portosystemic shunting. MRI spine typically normal. Treatment: shunt reversal with liver transplant.

Wilson disease: AR mutation in ATP7B[…] gene → prevents biliary copper excretion → accumulation in liver/brain. Half of patients have no hepatic disease at neurologic symptom onset. Neuropsychiatric: cognitive decline (frontostriatal pattern: judgment, attention, processing speed, dyscalculia), personality change, hypomania, depression.

Movement disorders: dystonia, tremor (low-amplitude postural/action ET-like, classic wing-beating[…] tremor = proximal UE with abducted/flexed posture), chorea, parkinsonism, ataxia.

Kayser-Fleischer rings[…] from corneal copper deposition (slit lamp).

Diagnostics: low serum ceruloplasmin (<14 likely, <5 highly predictive), high 24h urine Cu (>100/24h diagnostic if symptomatic), ATP7B[…] gene sequencing.

MRI: symmetric T2 hyperintensities in bilateral BG/thalamus/midbrain; ""face of giant panda[…]"" sign (lesion in midbrain tegmentum sparing red nuclei) + ""split thalamus"" sign.

Treatment: copper chelation (D-penicillamine or trientine[…]) + zinc + dietary Cu restriction (avoid shellfish). Start low, uptitrate slowly to minimize worsening risk; lifelong.

Hepatitis C: Painful peripheral neuropathy from small fiber[…] neuropathy; prevalence increases with disease duration + cryoglobulin positivity; Mixed cryoglobulinemia[…]: cold-induced palpable purpura + fatigue + arthralgias with severe vasculitic neuropathy; Higher risk of ischemic stroke from endothelial damage → atherosclerosis + vasculitis/APS; Treatment: direct-acting oral antivirals + rituximab if severe.

Bariatric surgery neurologic complications: Common deficiencies: B12, folate, B1/thiamine[…]; Thiamine deficiency in first 6 months: polyneuropathy + Wernicke encephalopathy + Korsakoff[…] syndrome; May develop orthostatic hypotension (higher after Roux-en-Y); Treatment: lifelong multivitamin supplementation.

Celiac disease / gluten-related disorders: Nearly all have HLA-DQ2 or DQ8[…] → anti-transglutaminase Ab deposits on cerebellar/brainstem vessels + Purkinje cell damage; Gluten ataxia[…]: progressive cerebellar ataxia + dysarthria + gaze-evoked nystagmus; Gluten neuropathy[…]: length-dependent axonal/small fiber or sensory ganglionopathy; MRI: cerebellar vermis atrophy[…] (vs global atrophy in genetic/degenerative); Diagnostics: antigliadin Ab[…] (very sensitive) → tissue transglutaminase Ab if negative but high suspicion; Treatment: gluten-free diet + treat vitamin deficiencies.

IBD: increased risk with MS[…] (genetics/brain-gut-microbiome).

TNF-α inhibitors[…] like natalizumab effective for both. Increased CVST and AIS risk. Medication neurotoxicities: metronidazole (axonal sensory neuropathy at high doses), thalidomide (neuropathy), TNFα inhibitors (CNS/PNS demyelinating).

Whipple disease (Tropheryma whipplei[…]): prodrome of migratory distal arthralgias → GI sx → neurologic (encephalopathy + supranuclear ophthalmoplegia + hypothalamic dysfunction + dysarthria + myoclonus + ataxia).

Classic: ""oculomasticatory myorhythmia[…]"" (slow rhythmic mouth + eye movements). Treatment: IV ceftriaxone 2-4 weeks + maintenance + monitor for IRIS.

Immune thrombocytopenia (ITP): PLT <100k. Primary or secondary (infection, meds, SLE, CLL). Can be vaccine-induced (VITT[…] after COVID vaccines → CVT). Treatment: corticosteroids + IVIG; PLT transfusion if life-threatening hemorrhage.

HIT (Heparin-induced thrombocytopenia): Ab against PF4-heparin[…] complexes typically 5-10 days after heparin exposure.

Diagnose with 4Ts[…] score + Ab testing.

Treatment: stop heparin + nonheparin AC (bivalirudin or fondaparinux[…]) → DOAC when stable. AVOID warfarin (worsens thrombosis in acute HIT). Autoimmune HIT: delayed/persistent despite heparin cessation → IVIG + PLEX. Essential thrombocythemia: JAK2 or CALR mutations → PLT >450k. Treatment: ASA + cytoreduction with hydroxyurea if high risk.

TMAs (Thrombotic microangiopathies): MAHA + thrombocytopenia + end organ injury.: TTP[…]: hereditary or acquired ADAMTS13 deficiency → large vWF multimers. DIC: secondary to sepsis/malignancy/obstetric complications.

HUS[…]: post-Shiga toxin (E. coli). Diagnostics: schistocytes + high LDH + low haptoglobin + ADAMTS13 testing.

Treatment: PLEX + corticosteroids[…].

Inherited thrombophilia: homozygous factor V Leiden, prothrombin G20210A, activated protein C resistance[…] very high risk. Arterial strokes often via paradoxical embolism via PFO. Routine testing NOT recommended. Test if <50yo with ESUS, CVT, R>L cardiac shunt, or personal/family history. Treatment: ASA for stroke vs AC for VTE.

APS (Antiphospholipid syndrome): Ab = lupus anticoagulant + anticardiolipin IgG/IgM + anti-β2 glycoprotein-I IgG/IgM[…]. Causes in situ thrombosis, intracardiac thrombi, Libman-Sacks endocarditis → cryptogenic stroke/TIA/unprovoked VTE + recurrent pregnancy loss. Must be positive on >2 occasions ≥3 months apart.

Treatment: warfarin[…] with INR 2-3 or 3-4 + ASA.

IgM paraprotein neuropathies: most target MAG (myelin-associated glycoprotein)[…] → demyelination.

Anti-MAG DADS (Distal Acquired Demyelinating Symmetric): Progressive distal sensory loss + paresthesias + sensory ataxia + postural tremor + reduced/absent ankle jerks; spares CN and autonomic; EMG/NCS: isolated distal demyelination — prolonged distal motor latencies + sensory slowing; DADS without anti-MAG = CIDP variant[…] → responds to IVIG; DADS with anti-MAG Ab → does NOT respond to IVIG.

CANOMAD[…]: Chronic Ataxic Neuropathy + Ophthalmoplegia + IgM + cold Agglutinins + Disialosyl Ab (anti-GD1b/GD3/GT1b/GQ1b).

1st-line treatment for anti-MAG and CANOMAD: rituximab[…] (anti-CD20). IgG/IgA paraprotein neuropathies and MM: Most common: slowly progressive length-dependent sensory neuropathy; Small proportion: CIDP-like presentation responsive to standard CIDP therapies; MM: direct axonal damage or chemotherapy SE (bortezomib, thalidomide) + vertebral damage → myelopathy/radiculopathy.

POEMS syndrome[…]: Polyneuropathy + Organomegaly + Endocrinopathy + Monoclonal gammopathy (often IgA or IgM with elevated lambda[…] light chain) + Skin changes.: Fastly progressive, sensorimotor, predominantly demyelinating, painful neuropathy + sclerotic bone lesions (not lytic like MM); Diagnostics: high serum VEGF[…]; Unlike CIDP: significant skin changes + NCS showing axonal changes + poor response to IVIG/steroids; Treatment: chemo-XRT + aSCT.

AL amyloidosis: from monoclonal light chain deposits.: Axonal sensorimotor neuropathy + autonomic + bilateral carpal tunnel[…] syndrome; Diagnostics: tissue biopsy (e.g., abdominal fat pad) with Congo red[…] stain showing apple-green birefringence; serum free light chain κ:λ ratio elevated; Treatment: daratumumab, bortezomib, dexamethasone, cyclophosphamide, aSCT. Neurolymphomatosis: lymphoma cells invade nerve roots/CN; most with non-Hodgkin lymphoma. Fastly progressive painful radiculopathy.

FDG-PET[…] guides biopsy. Intravascular large B-cell lymphoma: B-cell proliferation within small vessels → B symptoms + progressive dementia from subcortical strokes + neuropathy + torso/lower body rash. Diagnose with random skin biopsy or nerve biopsy.

Neuropsychiatric SLE: Symptoms: HA + psychosis + seizures + strokes (often APS[…] or intracranial vasculopathy) + rarely myelopathy (anti-AQP4 or MOG) + CN neuropathy (mostly CN VIII) + peripheral neuropathy; Diagnostics: ANA titer >1:80 required + neurologic symptoms within 6 months of SLE onset; MRI and LP/CSF generally nonspecific (may show OCBs); Treatment: corticosteroids + immunomodulatory (hydroxychloroquine[…]); antipsychotics if psychosis; AC if APS+.

Rheumatoid arthritis: Symmetric MCP/PIP/wrist/small foot joint inflammation; Spinal involvement: synovial joint inflammation (facet + atlantoaxial + atlantooccipital instability) → anterior or vertical subluxation[…] → brainstem compression; Meningitis: pachymeningeal or leptomeningeal enhancement; Peripheral neuropathy + carpal tunnel; rarely mononeuritis multiplex from rheumatoid vasculitis; Corticosteroids increase severe spinal involvement risk (osteopenic effects). Sjögren disease: Fatigue (most common disabling) + sicca syndrome (dry eyes/mouth) + rare longitudinally-extensive myelitis resembling NMO-AQP4 (also AQP4+) with possible optic neuritis.

Peripheral neuropathy or sensory ganglionopathy: may present with isolated trigeminal neuropathy[…], non-length-dependent small fiber neuropathy, or severe sensory ataxic gait. Asymmetric onset; EMG/NCS: preserved CMAPs + non-length-dependent decreased SNAPs.

Diagnostics: anti-Ro/SSA + La/SSB[…]. If negative, lip biopsy for focal lymphocytic sialoadenitis. Treatment: IVIG → rituximab or cyclophosphamide for vasculitis pattern.

Vasculitis classification by vessel size: Large: GCA, Takayasu arteritis[…]; Medium: PAN, Kawasaki[…]; Small: ANCA-associated, cryoglobulinemic, IgA.

Primary CNS vasculitis: HA + (notably) GPA[…] can cause pachymeningitis + mass-like meningeal/orbital lesions; LP/CSF: lymphocytic pleocytosis + high protein; MRI VWI: concentric[…] enhancement (vs eccentric in atherosclerosis); Angiographic "beading[…]" has poor sensitivity/specificity; Biopsy may be needed.

Peripheral vasculitis neuropathy: Mononeuritis multiplex[…] (most recognized; common in medium vessel e.g., PAN); Subacute progressive painful asymmetric neuropathy; Radiculoplexus neuropathy[…] (microvasculitis, e.g., diabetic amyotrophy); EMG/NCS: axonal pattern without demyelination.

Giant Cell Arteritis (GCA): Large vessel vasculitis affecting aorta or major branches[…] (carotids, vertebrals, axillary); Often comorbid polymyalgia rheumatica[…]; Symptoms: HA (variable location), jaw claudication[…] (specific, nonsensitive), temporal artery enlargement/TTP + vision loss from AION (ophthalmic artery)[…]; Complications: mostly posterior circulation AIS; Diagnostics: high ESR/CRP (unless steroids given); temporal artery biopsy[…] (granulomatous inflammation with giant cells + loss of smooth muscle and elastic fibers + focal skip lesions); color Doppler US may show "halo" sign; Treatment: start corticosteroids immediately → taper + immunotherapies (tocilizumab, upadacitinib).

Subtypes: Limited cutaneous[…]: distal sclerosis + Raynaud's[…] + anticentromere Ab + esophageal dysmotility + pulmonary HTN; Diffuse cutaneous[…]: proximal sclerosis + organ fibrosis + anti-topoisomerase I (anti-Scl-70) + anti-RNA polymerase III Ab. Myopathy: Serum CK may be elevated. MRI: muscle edema. EMG: myopathic pattern. Muscle biopsy: fibrosis (noninflammatory) or inflammatory myositis. Treatment: IVIG acutely → MMF chronically.

Avoid corticosteroids[…] due to risk of scleroderma renal crisis.

Peripheral neuropathy: Trigeminal neuropathy[…] may be a presenting sign with facial and oral numbness without lancinating pain (not trigeminal neuralgia) + absent corneal reflex; Mononeuropathy multiplex: painful, asymmetric, subacute; biopsy with perivascular inflammation + necrotizing vasculitis.

Central line placement — highest neurologic injury risk with internal jugular[…] vein (proximity to phrenic, recurrent laryngeal nerves, carotid artery, oculosympathetic tract).: Subclavian vein: brachial plexus, phrenic/recurrent laryngeal/axillary nerves; Intimal injury to carotid/subclavian → embolic stroke. Arterial line: radial → median or superficial radial nerves.

Endotracheal intubation: Tapia syndrome[…]: recurrent laryngeal + hypoglossal nerve injury → hypophonia + dysphagia + unilateral tongue paralysis; C-spine injury: MRI <72h for soft tissue assessment.

ECMO cannulation: VV-ECMO: ICH or AIS from microemboli, venous congestion, rapid PaCO2 decrease, BP changes/AC; VA-ECMO: higher rates with axillary or carotid artery cannulation; nonpulsatile arterial flow → can lead to ICH; North-South syndrome[…] in VA-ECMO: retrograde flow → upper body receives poorly oxygenated blood → upper body cyanosis + global cerebral hypoxia → decreased arousal.

ICU delirium: hyperactive (restless/agitated) vs hypoactive (lethargy/decreased arousal).: Risks: decreased cognitive reserve + frailty + illness severity; Risk meds: benzos, antihistamines, anticholinergics, opiates[…]; Pathophys: overactivity of DA and serotonin + underactivity of ACh + BBB disruption; 2025 guidelines: antipsychotics only for short-term acute agitation (not routine delirium prevention); benzos only for alcohol/benzo withdrawal; dexmedetomidine[…] superior to midazolam and equivalent to propofol for delirium outcomes (MENDS/MENDS2/SEDCOM).

Sepsis-associated encephalopathy: Pathophys: BBB disruption + endothelial dysfunction + microglial activation + cytokine release → disordered cerebral autoregulation → hypoxia; EEG: often triphasic waves[…] with periodic discharges; Treatment: MAP targets >65.

Antibiotic-associated encephalopathy: Type 1[…]: AMS + seizures/myoclonus within days of β-lactams[…] (cephalosporins/PCN); structurally similar to GABA → decreased release + competitively binds GABAa receptor; Type 2[…]: acute psychosis from quinolones, macrolides, sulfonamides; GABA inhibition + NMDA activation; Type 3[…]: subacute AMS + cerebellar dysfunction from metronidazole; MRI: symmetric T2 hyperintensity in cerebellar dentate or dorsal pons or splenium; Cefepime[…] most frequently associated with AMS especially in renal dysfunction (develops over ~4 days); trough levels >20 higher risk.

Wernicke encephalopathy: Classic triad: confusion + ataxia + ophthalmoplegia[…] (often in alcohol use disorder); MRI: symmetric T2 hyperintensities in medial thalami, mammillary bodies, PAG; Serum B1 may not be low; check intracellular function; Treatment: thiamine + magnesium[…] (Mg deficiency impairs thiamine function).

Critical illness neuromyopathy: Symmetric, proximal > distal[…] polyneuropathy sparing facial and extraocular muscles.

Critical illness polyneuropathy: Sensorimotor, axonal[…] neuropathy; NCS: low CMAPs with preserved conduction velocities; Nerve biopsy: axonal degeneration without inflammation.

Critical illness myopathy: EMG: long-duration CMAPs + fibrillation potentials + small polyphasic MUPs; Muscle biopsy: loss of myosin[…] + type II fiber decrease + myofibrillar disorganization + necrosis. Critical illness-associated diaphragm weakness: decreased diaphragm activity → muscle atrophy; increased activity with patient-vent dyssynchrony causes injury.

Test with transdiaphragmatic pressure by phrenic nerve stimulation[…]. Treatment: supportive care. Post-cardiac arrest brain injury: 2 stages — global ischemia during arrest, then disordered CBF post-ROSC (hyperemia → hypoperfusion). Seizures from excitotoxicity; treatment doesn't improve survival.

Trials showed no benefit of therapeutic hypothermia[…]. Treatment: optimize CPP + TTM + seizure control + manage edema.

Imaging: CTH with contrast[…] can be performed if indicated; iodinated contrast has no teratogenic effects; Preferred: MRI without contrast[…] or US; Gadolinium contrast crosses the placenta[…] → associated with fetal/neonatal death; TOF MRA/MRV for vascular evaluation.

Headache in pregnancy: New onset HA >20wk gestation or postpartum: rule out preeclampsia[…] (check BP + urine protein); Highest cerebrovascular HA risk: late 3rd trimester and especially early postpartum.

Acute abortive treatments: 1st line: Tylenol + caffeine OR Reglan + Benadryl[…]; Sumatriptan (preferred triptan); NSAIDs only in 2nd trimester (risk of premature ductus arteriosus closure[…] in 1st and 3rd trimesters); Prednisone/prednisolone do NOT enter fetal circulation (inactivated by 11β-hydroxysteroid dehydrogenase in placenta); Ergots[…] contraindicated (uterine contractions + vasospasm); Avoid dexamethasone (not inactivated).

Chronic preventive: 1st line: Botox, β-blockers, CCBs, TCA/SNRI[…]; Stop CGRP mAbs 6 months before planned conception; stop -geptans 1 week before; Avoid valproate and topiramate[…] (teratogenic). IIH in pregnancy: ACTZ OK after 20 weeks. Avoid topiramate/zonisamide. If fulminant vision loss → C-section to limit Valsalva.

Postdural puncture HA: improves when supine[…]. Narrower-gauge needles reduce risk. Treatment: hydration + analgesia + caffeine (max 900 mg/day, 300 if breastfeeding) → epidural blood patch if refractory (higher chance after 48h).

Preeclampsia/eclampsia: triples HTN risk and doubles stroke/heart disease risk long-term. Treatment: IV labetalol or nicardipine[…] short-term + IV Mg[…] for eclampsia. If refractory: workup for PRES, CVST, or ICH.

RCVS in pregnancy: risk factors include preeclampsia, triptans, SSRIs/SNRIs[…]. Treat with CCBs; avoid triptans.

AIS: IV thrombolytic does NOT cross the placenta[…] and should be considered for moderate-severe stroke + EVT. ASA low-dose (doses >150 mg not recommended after 28 weeks).

Majority of strokes occur in 3rd trimester (near delivery) and first 2 weeks postpartum[…]. CVST: treat with LMWH; AVOID warfarin (teratogenic) and DOACs (limited safety data).

Risk of CVST goes up 5x during pregnancy and 60x in first 12 weeks postpartum[…]. ICH/SAH: tied to causes above or aneurysmal rupture. Amniotic fluid embolism: fetal tissue/Ag → proinflammatory response → most common cause of peripartum cardiac arrest with onset during or immediately after placental delivery.

Can trigger DIC[…].

Epilepsy in pregnancy: Safest ASMs: lamotrigine, levetiracetam, oxcarbazepine[…]; Highest teratogenic risk: valproate[…]; Do NOT remove well-controlled ASMs once pregnant (neurulation occurred; changes 2x risk); Start folic acid >0.4 mg; ASM levels decrease[…] during pregnancy (lamictal, keppra, oxcarb, vimpat, zonisamide) — get preconception levels then monthly.

MS in pregnancy: pregnancy generally REDUCES[…] relapse rates except when discontinuing natalizumab or S1P modulators[…] → rebound relapse risk.

NMOSD in pregnancy: pregnancy INCREASES[…] relapse risk; also associated with miscarriage/preeclampsia (AQP4 expression in placenta).

Use prednisolone (inactivated by placental enzyme); avoid dexamethasone[…].

Long-term: eculizumab[…] appears safe.

MG in pregnancy: Exacerbations more in 1st trimester + postpartum[…]; PO pyridostigmine safe; IV AChE inhibitors may produce uterine contractions (avoid until labor); IV Mg contraindicated in MG (precipitates myasthenic crisis[…]) → use keppra for eclampsia; Avoid neuromuscular blocking agents.

Peripartum neuropathy: most commonly femoral and lateral femoral cutaneous[…] nerves (large fetus, prolonged 2nd stage).

Delivery considerations: Valsalva[…] → herniation risk in patients with space-occupying lesion or CSF obstruction above foramen magnum → deliver via C-section with general anesthesia; Stable IIH: vaginal delivery OK; Unruptured aneurysm: vaginal delivery generally safe; SCI above T6[…]: monitor for autonomic dysreflexia from uterine contractions. Neuraxial anesthesia complications: if local anesthetic enters subdural or subarachnoid space → ascending weakness → phrenic nerve paralysis → cardiorespiratory depression. Typical course: perioral paresthesia with metallic taste → seizures → cardiac arrest.

Treatment: elevate HOB + supportive + emergent delivery + IV lipid emulsion[…]. Menopause: Migraines: variable course depending on type (with/without aura, catamenial); Stroke risk increases; consider transdermal estrogen; Epilepsy: may increase perimenopausal but typically stabilizes postmenopausal; watch decrease in lamotrigine concentration; MS: higher risk of progression postmenopausally.

Opioids: Fentanyl[…] more potent, shorter-acting, cheaper than heroin → more overdose deaths. Standard UTox does NOT detect fentanyl.

Heroin-associated toxic encephalopathies: Spongiform leukoencephalopathy[…] ("chasing the dragon" = inhaling heated heroin vapors): progressive apathy + cerebellar signs + spastic quadriparesis. MRI: confluent symmetric white matter diffusion restriction + T2 hyperintensities in cerebellar white matter + posterior limb internal capsule, sparing subcortical U-fibers. Opioid-associated amnestic syndrome: profound anterograde amnesia.

MRI: diffusion restriction in hippocampi + globus pallidi[…].

Chanter syndrome[…]: restricted diffusion of cerebellum, hippocampi, basal ganglia leading to coma; risk of cerebellar edema/obstructive hydro requiring decompression. Pounce syndrome (kids): quadriparesis, seizures, AMS, ataxia; symmetric cerebellar diffusion restriction. Heroin-associated myelopathy: complete transverse myelopathy especially in users who resume after period of abstinence. MRI: longitudinally extensive T2 hyperintensity, typically cervical or thoracic. Opioid withdrawal: tolerance develops within days-weeks; withdrawal within hours of last dose. Neonatal abstinence syndrome: feeding difficulties + tremor + myoclonus + seizures. Stimulants: Methamphetamine: increases release + blocks reuptake of DA/serotonin/NE; longer half-life than cocaine. Cocaine: shorter half-life; snorted ~30-60 min, crack ~5-10 min to effect. Cerebrovascular effects: ICH from HTN (deep structures), SAH from aneurysmal rupture, AIS from accelerated atherosclerosis/cardiomyopathy/arrhythmias/dissection.

β-blockers[…] historically avoided (unopposed α activity fear) but several studies demonstrate safety/efficacy in stimulant toxicity. Psychosis: auditory > visual/tactile + delusions; often resolves within 1 month.

Punding[…]: compulsive repetitive non-goal-directed tasks (also seen in PD patients on DA meds). Choreoathetoid movements + bruxism + tremor + dystonia + orolingual dyskinesias.

Levamisole[…] (cocaine cutting agent): demyelination within days-weeks; MRI bilateral white matter FLAIR + patchy/ring enhancement. Treatment: IVMP ± IVIG/PLEX/cyclophosphamide.

Hallucinogens: psychedelics (LSD/psilocybin/ayahuasca/mescaline) — no classic withdrawal syndrome. Hallucinogen Persisting Perception Disorder[…]: prolonged visual symptoms (altered motion, halos, palinopsia, macropsia/micropsia) lasting weeks-months.

MDMA: tachycardia/HTN/bruxism/trismus/tremor/myoclonus/fever; severe → serotonin syndrome + rhabdo + hyponatremia[…] (polydipsia + ADH secretion).

Treatment: supportive + cooling + cyproheptadine[…] for serotonin syndrome; avoid serotonergic agents (including fentanyl).

Ketamine (NMDA blocker): ketamine bladder syndrome[…] (urinary frequency/urgency/pain → permanent dysfunction); chronic use → executive function decline + memory impairment.

PCP (NMDA blocker): anxiety + paranoia + hallucinations + agitation + cerebellar signs + muscle rigidity (→ rhabdo) + movement disorders (myoclonus, dystonia) + vertical or horizontal nystagmus[…]. Classically agitated and violent.

Dextromethorphan: sigma opioid agonist + 5-HT2 agonist (serotonin syndrome risk); high doses block NMDA → dissociative state + bromism[…] (HA, dysarthria, memory issues).

Sedatives: flumazenil[…] can precipitate withdrawal seizures in chronic benzo users. GHB at high doses → coma that suddenly reverses after several hours. Novel psychoactive: synthetic cathinones ("bath salts") cause stimulant effects (psychosis/aggression/seizures/rhabdo); NOT detected on standard UTox.

NBOMes[…] (5-HT2A agonists): potent psychedelic + serotonin syndrome + seizures + toxic leukoencephalopathy. Nitrous oxide: converts B12 to inactive form → inhibits methionine synthase → impairs myelin and DNA synthesis. Chronic use → myelopathy/neuropathy/myeloneuropathy.

Serum B12 may be normal; MMA[…] often elevated. MRI: T2 hyperintensity in dorsal columns (especially cervical).

Huffing: chronic n-hexane[…] (petrol, glues) → painful axonal peripheral neuropathy.

Chronic toluene[…] → toxic leukoencephalopathy with diffuse white matter T2 hyperintensity.

Cannabis: dose-response with stroke; cannabis hyperemesis[…] syndrome (recurrent N/V/abd pain relieved by hot baths; treatment is cessation). CBD FDA-approved for Lennox-Gastaut, Dravet, TSC. Synthetic cannabinoids (K2/Spice) → more toxic; can precipitate seizures, AIS, ICH/SAH.

Injection drug use: increases risk of infective endocarditis → embolic strokes + brain abscesses + spinal epidural abscess + mycotic aneurysms[…] (may rupture → SAH).

Skin popping increases risk of wound botulism[…] (black tar heroin).

Pituitary adenomas: Macroadenomas (>10mm) can exert mass effect; HA: most often migraine vs primary stabbing vs SUNCT vs cluster semiology; Bitemporal hemianopsia[…] (optic chiasm compression) vs junctional scotomas[…] (ipsilateral central + contralateral superior temporal field) vs RAPD; Cavernous sinus extension → diplopia.

Functional adenomas: Prolactinomas[…] (most are microadenomas): dysmenorrhea + galactorrhea + osteoporosis.

Note transient PRL elevation can be seen with seizures[…] (propagate via mesial temporal to hypothalamus; ~double baseline 10-20 min after, poor sensitivity) and syncope.

Acromegaly (GH)[…]: increased limb/connective tissue size → OSA (tongue/pharyngeal) + carpal tunnel + reduced exercise tolerance + joint pains.

Treatments: DA agonists[…] for prolactinomas; somatostatin analogs for GH tumors; Escalate to transsphenoidal surgery ± XRT.

Pituitary apoplexy: acute hemorrhage/infarction of pituitary; triggers include HTN, AC use, head trauma/surgery.: Symptoms: sudden thunderclap HA[…] (stretches dura) + n/v ± compression effects (optic chiasm → bitemporal; optic nerve → decreased acuity; CN III → diplopia/ptosis); CT has low sensitivity vs MRI for apoplexy; Treatment: high-dose corticosteroids + transsphenoidal resection + lifelong hormone replacement.

Posterior pituitary: DI[…]: vasopressin deficiency → polyuria/polydipsia + can't concentrate urine.

SIADH[…]: vasopressin excess → water retention → hyponatremia → AMS + seizures. Cautious correction (ODS risk). Empty sella: herniation of suprasellar arachnoid + subarachnoid CSF into sella turcica.

Seen in most patients with IIH[…].

Hyperthyroidism (most often Graves[…] disease): Anxiety/heat intolerance/diaphoresis/insomnia/weight loss + Graves ophthalmopathy (proptosis + strabismus from Ab targeting EOM); CNS: enhanced physiologic tremor + hyperreflexia + AMS + decreased seizure threshold + increased cardioembolic stroke risk from AFib[…]; PNS: proximal > distal myopathy with normal CK; thyrotoxic periodic paralysis[…] (sudden limb weakness from exercise or high carbs, similar to hypokalemic PP); increased MG risk; Treatment: nonselective β-blockers; K+ supplementation for thyrotoxic PP. Hypothyroidism (most often Hashimoto): Depression/cold intolerance/fatigue/weight gain.

Myxedema coma[…]: AMS + hypothermia ± seizures + cardiac (hypoTN/bradycardia) + respiratory (hypoventilation) + metabolic (hypoglycemia/hyponatremia).

CNS: cognitive issues → increased dementia risk + psychosis + Woltman sign[…] (delayed muscle stretch reflex relaxation).

Hashimoto encephalopathy[…]: aka "steroid-responsive encephalopathy" associated with autoimmune thyroiditis; (+) anti-thyroglobulin and/or anti-TPO Ab with subacute AMS, responds to immunotherapy. PNS: proximal > distal myopathy with CK often >10x ULN + sensory-predominant neuropathy.

Adrenal insufficiency: Primary (Addison, TB, adrenal hemorrhage): decreased glucocorticoid + mineralocorticoid → high ACTH/CRH; Secondary (pituitary or chronic exogenous corticosteroid use abruptly discontinued): low ACTH → cortisol deficiency; ALD preserved; Adrenal crisis[…]: hypotensive + hypoglycemic + hyponatremia + hyperkalemia → seizures/coma; PNS: proximal > distal myopathy with normal CK/EMG; sensory or autonomic neuropathy; Treatment: glucocorticoids + fluids + electrolyte correction.

Cushing syndrome (from prolonged cortisol exposure): Central obesity + moon facies + buffalo hump + acne + glucose intolerance + osteoporosis + purple striae; CNS: cognitive impairment → cortical and hippocampal atrophy[…]; PNS: steroid myopathy[…] — gradually progressive, painless, LE > UE weakness with normal CK; EMG with myopathic features but no fibrillation potentials; biopsy with type II fiber atrophy.

Diabetic peripheral neuropathy: axonal, gradual, sensory, length-dependent — starting in feet → calves/ankles → fingers/hands in stocking-glove[…] distribution. Exam: Achilles hyporeflexia. Severe: autonomic involvement (orthostatic hypoTN, gastroparesis, sexual dysfunction).

Treatment: manage DM + gabapentinoids, SNRIs (duloxetine), TCAs, Na+ channel blockers (lamictal/oxcarb)[…] + capsaicin cream. Diabetic thoracic radiculopathy: affects one thoracic nerve root → severe unilateral neuropathic pain in chest/abdomen, does NOT cross midline, worse at night. Treatment: symptomatic. Diabetic Lumbosacral Radiculoplexus Neuropathy (Diabetic Amyotrophy): Immune-mediated focal microvasculitis → ischemic injury to lumbosacral plexus; Risk: rapid DM control + weight loss (rarely also with GLP-1 agonists); Unilateral acute pain + allodynia in proximal LE → subacute weakness (proximal > distal); MRI lumbosacral plexus: T2 hyperintensity + thickening ± enhancement; Treatment: IVMP and early immunotherapies studied. Treatment-induced neuropathy of DM: rapid BG control → acute-onset severe burning pain symmetrically affecting distal regions + autonomic dysfunction.

Risk proportional to magnitude and rate of HbA1c change[…]. CNS disorders in DM: Stroke: from accelerated atherosclerosis.

DKA more common in type 1; nonketotic hyperosmolar coma (HHS)[…] more common in type 2 → AMS, rarely cerebral edema.

Diabetic striatopathy[…]: unilateral hemichorea or hemiballism in uncontrolled DM.

MRI: unilateral T1 hyperintensity in striatum contralateral[…] to movement disorder. Treatment: DA blockers.

Hyperglycemia-induced occipital lobe seizures[…]: in nonketotic hyperosmolar coma → homonymous hemianopia + visual hallucinations. EEG: contralateral occipital seizures; MRI: T2 hyperintensity in occipital cortex.

Osmotic Demyelination Syndrome (CPM) shows symmetric T2 hyperintensity in the central basis pontis[…] with a trident or bat-shape[…] due to preferential horizontal tract involvement, sparing vertical tracts. Classically occurs after correction of severe hyponatremia with hypertonic saline.

Cefepime[…] is most frequently associated with encephalopathy especially in renal dysfunction[…]; develops over ~4 days; trough levels >20 place higher risk. Beta-lactams cause Type 1 antibiotic-associated encephalopathy via GABA inhibition.

Wilson disease: AR mutation in ATP7B[…]; copper accumulates in liver/brain/cornea.

Diagnostics: low serum ceruloplasmin[…] (<5 highly predictive), 24-hour urine copper >100, ATP7B sequencing.

MRI: "face of giant panda[…]" sign (midbrain tegmentum sparing red nuclei).

Treatment: D-penicillamine or trientine[…] + zinc + dietary copper restriction.

Suspected GCA with elevated ESR/CRP and systemic symptoms → immediate corticosteroids[…] BEFORE temporal artery biopsy. Skip lesions on biopsy may need multiple sections.

Color Doppler US may show "halo[…]" sign.

Maintenance: tocilizumab[…] (IL-6 inhibitor).

The best way to prevent strokes from sickle cell vasculopathy is chronic exchange transfusions[…] to lower HbS and stop sickled cells from blocking brain vessels.

Annual TCD[…] from ages 2-16.

Hydroxyurea[…] at max tolerated dose is alternative.

Antiphospholipid Syndrome requires positive Ab on >2 occasions at least 3 months apart[…].

Ab panel: lupus anticoagulant + anticardiolipin IgG/IgM + anti-β2 glycoprotein-I IgG/IgM[…]. Treatment: warfarin with INR 2-3 or 3-4 + ASA. AC can cause false +/- for lupus anticoagulant — delay testing 1-2 weeks after stopping VKA.

Diabetic lumbosacral radiculoplexus neuropathy (diabetic amyotrophy) is often seen with rapid DM control and weight loss[…].

Immune-mediated focal microvasculitis[…] → ischemic nerve injury. Treatment: IVMP and early immunotherapies.

Treatment of Wernicke encephalopathy requires thiamine[…] supplementation AND magnesium[…] replacement — Mg deficiency impairs thiamine function. Serum thiamine may not be low (doesn't correlate well with intracellular).

PRES (Posterior Reversible Encephalopathy Syndrome) risk factors include HTN, eclampsia, tacrolimus[…] use. Often presents in late 3rd trimester or early postpartum. Differential includes RCVS in pregnancy (risk factors: preeclampsia, triptans, SSRIs/SNRIs; treat with CCBs).