Last Minute Review
Neuroimmunology — Last Minute Review
A last-minute review of high-yield facts — dense tables and one-liners for RITE/Board prep. Not a substitute for the full notes.
McDonald Criteria (2024 Revision) — MS Diagnosis
| Criterion | 2024 Requirement | How to Fulfill |
|---|---|---|
| DIS (Dissemination in Space) | ≥1 T2 lesion in ≥2 of 5 CNS regions | Periventricular, cortical/juxtacortical, infratentorial, spinal cord, optic nerve (NEW) — need ≥2 of 5 areas |
| DIT (Dissemination in Time) | No longer strictly required if other evidence supports MS | DIT can be met by: new T2/Gd+ lesion on follow-up MRI, simultaneous Gd+ and non-enhancing lesions, or CSF OCBs/kappa free light chains |
| RIS (Radiologically Isolated Syndrome) | Can now meet MS diagnostic criteria without clinical symptoms | NEW: MRI findings consistent with DIS + supportive biomarkers (OCBs, central vein sign, paramagnetic rim lesions) — no clinical attack required |
Key 2024 vs 2017 Changes
| Feature | 2017 Criteria | 2024 Criteria |
|---|---|---|
| DIS regions | 4 regions (periventricular, cortical/juxtacortical, infratentorial, spinal cord) | 5 regions — optic nerve added as 5th location (via MRI orbits, OCT, or VEP) |
| DIT requirement | Strictly required for diagnosis | Removed as strict requirement — diagnosis possible after single event if other evidence supports |
| New biomarkers | OCBs only | OCBs + central vein sign, paramagnetic rim lesions, kappa free light chains (CSF) |
| RIS | Not diagnostic — must await symptoms | Can qualify for MS diagnosis if DIS + supportive biomarkers |
| Special populations | Limited guidance | Specific guidance for children and adults ≥50 years |
| CIS category | CIS = first event, not yet MS | Many former CIS cases now diagnosable as MS at first presentation |
| DIS Region (5 total) | Evidence |
|---|---|
| Periventricular | ≥1 T2 lesion (changed from ≥3 in 2017) |
| Cortical/juxtacortical | ≥1 lesion |
| Infratentorial | ≥1 lesion |
| Spinal cord | ≥1 lesion |
| Optic nerve (NEW) | MRI optic nerve lesion, abnormal OCT (RNFL thinning), or abnormal VEP |
💎 Board Pearl
The 3 biggest 2024 updates: (1) Optic nerve = 5th DIS region (use MRI orbits, OCT, or VEP), (2) DIT no longer strictly required — diagnosis possible at first presentation, (3) RIS can now = MS with supportive biomarkers. New supportive biomarkers: central vein sign (≥40% of lesions), paramagnetic rim lesions, and CSF kappa free light chains. Periventricular lesion threshold reduced from ≥3 to ≥1.MS vs NMOSD vs MOGAD
| Feature | MS | NMOSD (AQP4+) | MOGAD |
|---|---|---|---|
| Antibody | None specific (OCBs in CSF) | AQP4-IgG (serum; ~80% sensitivity) | MOG-IgG (serum; CBA preferred) |
| Sex ratio (F:M) | ~3:1 | ~9:1 | ~1:1 |
| Age at onset | 20–40 | 30–50 | Bimodal: children + young adults |
| ON features | Unilateral, mild, retrobulbar, good recovery | Severe, often bilateral, posterior > anterior, poor recovery | Bilateral, anterior predominant, disc edema, perineural enhancement, good recovery |
| Myelitis | Short segment (<3 vertebral segments), peripheral | LETM (≥3 segments), central gray matter, bright spotty lesions | LETM, conus/lower cord predilection |
| Brain MRI | Dawson fingers, periventricular ovoid lesions perpendicular to ventricles | Often normal early; area postrema, periaqueductal, diencephalic, cloud-like enhancement | Fluffy bilateral cortical/deep WM, ADEM-like in children |
| Spinal MRI | Short lesions, dorsolateral, incomplete ring enhancement | LETM (≥3 segments), central cord, may enhance diffusely | LETM, conus involvement, can mimic NMOSD |
| CSF OCBs | Present >95% | Usually absent (~15–20%) | Usually absent |
| Relapse pattern | Relapses then progressive phase (SPMS) | Relapsing >90%; rarely monophasic | ~50% monophasic, ~50% relapsing |
| Acute treatment | IV methylprednisolone | IV methylprednisolone + early PLEX | IV methylprednisolone (very steroid-responsive); PLEX if refractory |
| Maintenance treatment | DMTs (interferons, anti-CD20, S1P modulators, etc.) | Rituximab, eculizumab, satralizumab, inebilizumab, azathioprine, mycophenolate | No FDA-approved DMT; azathioprine, mycophenolate, rituximab if relapsing |
| MS DMTs harmful? | — | YES — interferons, fingolimod, natalizumab worsen NMOSD | Likely — interferons, fingolimod should be avoided |
| Prognosis | Variable; disability accrues over decades | Poor recovery per attack; cumulative disability from relapses | Generally good recovery per attack; better than NMOSD |
Clinical Pearl
Do NOT treat NMOSD with MS DMTs — interferon-β, fingolimod, and natalizumab can worsen NMOSD attacks. Always confirm AQP4 status before starting MS-specific DMTs in patients with LETM or severe/bilateral ON.💎 Board Pearl
Area postrema syndrome (intractable nausea/vomiting/hiccups) is nearly pathognomonic for NMOSD. MOG-IgG titers can become negative over time — persistent positivity predicts relapsing course. MOGAD optic neuritis shows characteristic perineural enhancement (around the nerve sheath, not just the nerve). NMOSD bright spotty lesions on T2 = high specificity.MS Disease-Modifying Therapies
| DMT | Route | MOA | Monitoring | Key Risk | Efficacy Tier |
|---|---|---|---|---|---|
| Interferon-β | IM/SC (varies by formulation) | Immunomodulatory, ↓ BBB disruption | CBC, LFTs q3–6mo | Flu-like symptoms, hepatotoxicity, depression | Moderate |
| Glatiramer acetate | SC daily or 3×/week | MBP mimic → Th2 shift | None required | Injection site reactions, lipoatrophy, post-injection reaction | Moderate |
| Teriflunomide | PO daily | DHODH inhibitor → ↓ pyrimidine synthesis | LFTs monthly ×6mo then q6mo; TB test before start | Teratogenic (Category X); hepatotoxicity; hair thinning | Moderate |
| Dimethyl fumarate | PO BID | Nrf2 pathway activation | CBC q6mo (lymphocytes!) | Lymphopenia → PML; GI; flushing | Moderate |
| Fingolimod | PO daily | S1P modulator → lymphocyte sequestration in LN | First-dose 6hr cardiac monitoring; ophthalmology 3–4mo; CBC; LFTs | Bradycardia/AV block (first dose); macular edema; PML; VZV; rebound | High |
| Siponimod | PO daily (dose titration) | S1P1/S1P5 selective | CYP2C9 genotype before start; cardiac monitoring; ophthalmology | Bradycardia; macular edema; *3/*3 genotype = contraindicated | High (approved for active SPMS) |
| Ozanimod | PO daily (7-day titration) | S1P1/S1P5 selective | CBC, LFTs, ECG, ophthalmology | Bradycardia; macular edema; avoid with MAOIs | High |
| Cladribine | PO short courses (Year 1 + Year 2 only) | Purine analog → selective lymphocyte depletion | CBC before each course | Lymphopenia; infections; malignancy concern | High (immune reconstitution) |
| Natalizumab | IV q4 weeks | Anti-α4-integrin → blocks lymphocyte CNS entry | JCV Ab q6mo; MRI q3–6mo | PML (JCV+, prior IS, >2 years) | High |
| Ocrelizumab | IV q6 months | Anti-CD20 (humanized) → B-cell depletion | Hep B screen; IgG levels; CBC | Infusion reactions; infections; breast cancer signal | High (first PPMS approval) |
| Ofatumumab | SC monthly (after loading) | Anti-CD20 (fully human) | Hep B screen; IgG levels | Injection reactions; infections; ↓ immunoglobulins | High |
| Alemtuzumab | IV ×5d (year 1), ×3d (year 2) | Anti-CD52 → profound lymphocyte depletion | CBC + TFTs monthly ×4 years after last dose; urinalysis monthly; skin exams | Secondary autoimmunity (thyroid 40%, ITP, anti-GBM); stroke; MI | High (REMS program) |
| Mitoxantrone | IV q3 months (lifetime dose limit) | Topoisomerase II inhibitor → immunosuppression | Cardiac echo before and during; CBC | Cardiotoxicity (cumulative dose limit 140 mg/m²); AML risk | High (rarely used now) |
PML Risk Stratification (Natalizumab)
| Risk Factor | Detail |
|---|---|
| JCV antibody status | Negative = very low risk (~0.1/1000); positive = stratify further |
| JCV antibody index | >1.5 = significantly higher risk; ≤0.9 = lower risk among JCV+ patients |
| Prior immunosuppression | ↑↑ risk if prior azathioprine, MTX, mitoxantrone, cyclophosphamide |
| Natalizumab duration | Risk ↑ after 24 months; highest at 24–72 months |
| Highest risk group | JCV Ab+ with index >1.5 + prior IS + >2 years → ~13/1000 |
| Extended interval dosing | Q6–8 week dosing may ↓ PML risk (observational data) |
💎 Board Pearl
JCV risk trifecta: anti-JCV Ab index >1.5, prior immunosuppression, natalizumab >2 years. S1P first-dose cardiac monitoring: required for fingolimod (6 hrs) and siponimod; ozanimod/ponesimod use gradual titration instead. Glatiramer = safest in pregnancy (Category B). Teriflunomide = Category X, requires cholestyramine washout. Anti-CD20 agents do NOT deplete plasma cells (CD20−). Alemtuzumab monitoring continues 4 years after LAST dose. Rebound risk: S1P modulators and natalizumab carry high rebound if stopped without bridging. DMF PML: occurs with ALC <500 for >6 months — stop drug.Acute Relapse Treatment Protocol
| Step | Treatment | Dose | Duration | Notes |
|---|---|---|---|---|
| First-line | IV Methylprednisolone | 1 g IV daily | 3–5 days | Speeds recovery but does NOT change long-term disability in MS; consider oral taper; very steroid-responsive in MOGAD |
| Second-line | PLEX (Plasma Exchange) | 5–7 exchanges | Over 10–14 days | Start early for best response; especially effective in NMOSD and severe MS relapses refractory to steroids |
| Alternative second-line | IVIg | 2 g/kg total | Over 2–5 days | Used when PLEX unavailable; check IgA deficiency before first infusion (anaphylaxis risk) |
| Rescue / refractory | Rituximab | 1000 mg IV ×2 (days 0, 14) | Effect in weeks | For autoimmune encephalitis, refractory NMOSD, aggressive MS; Hep B screening mandatory |
| Rescue / refractory | Cyclophosphamide | 500–1000 mg/m² IV | Monthly pulses | For PACNS induction, refractory autoimmune encephalitis, severe SLE; give MESNA for bladder protection |
💎 Board Pearl
PLEX is most effective for NMOSD relapses and severe MS relapses refractory to steroids — start early (within days), delays significantly reduce efficacy. NMOSD FDA-approved maintenance therapies (AQP4+): eculizumab, satralizumab, inebilizumab — all require AQP4-IgG positivity. Eculizumab: meningococcal vaccination at least 2 weeks before first dose. Check TPMT before azathioprine; check IgA before IVIg.Autoimmune Encephalitis — Antibody Table
| Antibody | Target | Key Syndrome | Associated Tumor | Age/Sex | Treatment Response |
|---|---|---|---|---|---|
| Anti-NMDAR | NR1 subunit (cell-surface) | Psychiatric → seizures → dyskinesias → autonomic instability → central hypoventilation | Ovarian teratoma (young women) | Young women; F>>M | Excellent if treated early + tumor removal |
| Anti-LGI1 | LGI1 (cell-surface) | Limbic encephalitis: memory loss, confusion, temporal seizures, hyponatremia (SIADH) | Rare (<10%) | Older men (50–70) | Good; responds to immunotherapy |
| Anti-CASPR2 | CASPR2 (cell-surface) | Morvan syndrome (encephalitis + peripheral nerve hyperexcitability + autonomic dysfunction + insomnia) | Thymoma (~20%) | Older men | Good; may need prolonged therapy |
| Anti-GABAB | GABA-B receptor (cell-surface) | Limbic encephalitis with prominent, refractory seizures | SCLC (~50%) | Older adults | Moderate; tumor treatment critical |
| Anti-AMPAR | AMPA receptor (cell-surface) | Limbic encephalitis; frequent relapses | Lung, breast, thymoma (~65%) | Older women | Good; high relapse rate |
| Anti-DPPX | DPPX (cell-surface) | Prodromal severe diarrhea/weight loss → encephalitis + hyperekplexia | Rare | Adults | Good |
| Anti-IgLON5 | IgLON5 (cell-surface) | NREM/REM parasomnia + bulbar dysfunction + gait instability; tauopathy on pathology | None | Older adults; HLA-DRB1*10:01 | Poor; progressive despite therapy |
| Anti-GlyR | Glycine receptor (cell-surface) | PERM (progressive encephalomyelitis with rigidity and myoclonus); stiff-person spectrum | Rare | Adults | Better than anti-GAD SPS |
💎 Board Pearl
Faciobrachial dystonic seizures (FBDS) = pathognomonic for anti-LGI1 — brief, frequent, AED-resistant, immunotherapy-responsive. Treat early to prevent cognitive decline. Extreme delta brush on EEG (rhythmic delta + superimposed beta) = anti-NMDAR encephalitis. Anti-NMDAR encephalitis can follow HSV encephalitis (post-infectious autoimmune mechanism). Hyponatremia + limbic encephalitis = think LGI1. CSF antibody more sensitive than serum for NMDAR; serum more sensitive for LGI1.Paraneoplastic Antibodies — Intracellular (Poor Prognosis)
| Antibody | Syndrome | Associated Tumor | Response to Immunotherapy |
|---|---|---|---|
| Anti-Hu (ANNA-1) | Sensory neuropathy, encephalomyelitis, limbic encephalitis, autonomic neuropathy | SCLC | Poor — most common paraneoplastic Ab; multifocal dysfunction |
| Anti-Yo (PCA-1) | Subacute pancerebellar degeneration (irreversible Purkinje cell loss) | Ovarian, breast | Poor — essentially irreversible once established; treat tumor first |
| Anti-Ri (ANNA-2) | Opsoclonus-myoclonus-ataxia, brainstem encephalitis | Breast, SCLC | Partial — may improve with tumor treatment |
| Anti-CV2 (CRMP5) | Chorea + peripheral neuropathy, optic neuritis, uveitis | SCLC, thymoma | Poor — chorea + neuropathy combo is characteristic |
| Anti-amphiphysin | Stiff-person syndrome, encephalomyelitis | Breast, SCLC | Poor — paraneoplastic SPS variant (vs anti-GAD65 SPS) |
| Anti-Ma2 (Ta) | Limbic/diencephalic encephalitis, narcolepsy, vertical gaze palsy | Testicular germ cell (young men); lung (older) | Moderate — better prognosis if testicular tumor (curable) |
| Anti-SOX1 | Lambert-Eaton myasthenic syndrome, cerebellar ataxia | SCLC | Poor — often co-occurs with anti-VGCC; supports SCLC association |
| Anti-GAD65 | Stiff-person syndrome, cerebellar ataxia, temporal lobe epilepsy | Rarely paraneoplastic (thymoma, SCLC if tumor); usually autoimmune | Variable — very high titers (>10,000) = neurological; low titers = type 1 DM |
Clinical Pearl
Intracellular antibodies (Hu, Yo, Ri, CV2, amphiphysin, Ma2) = T-cell mediated neuronal destruction = poor response to immunotherapy = FIND AND TREAT THE TUMOR. Cell-surface antibodies (NMDAR, LGI1, CASPR2, AMPAR, GABA-B, VGCC) = antibody-mediated = potentially reversible with immunotherapy + tumor removal.💎 Board Pearl
Young man + limbic encephalitis + hypersomnia + vertical gaze palsy = anti-Ma2 → check for testicular tumor. Opsoclonus-myoclonus in adults = anti-Ri or lung cancer; in children = neuroblastoma. LEMS: anti-VGCC (P/Q-type), SCLC ~60%, proximal weakness + areflexia + facilitation on high-frequency rNS, treat with 3,4-DAP. Neurological symptoms often PRECEDE cancer diagnosis by months to years.Systemic Autoimmune Diseases — Neuro Manifestations
| Disease | CNS Features | PNS Features | Key Test | Treatment |
|---|---|---|---|---|
| Neurosarcoidosis | CN VII palsy (most common CN), leptomeningeal enhancement, hypothalamic/pituitary lesions (DI), chronic meningitis, myelopathy (dorsal subpial) | Small fiber neuropathy (most common PNS), mononeuritis multiplex | Chest CT (bilateral hilar LAD); ACE (low sensitivity ~60%); non-caseating granulomas on biopsy; PET-CT for biopsy targets | Steroids → MTX/AZA/MMF → infliximab (refractory) |
| Neuro-Behçet | Brainstem/diencephalic encephalitis, cerebral venous sinus thrombosis, cranial neuropathies | Rare | Clinical criteria (oral ulcers + 2 of: genital ulcers, eye lesions, skin lesions, pathergy); HLA-B51 | Steroids + azathioprine; anti-TNF for refractory; anticoagulation for CVST |
| SLE (neuropsychiatric) | Psychosis, seizures, cognitive dysfunction, stroke (antiphospholipid), transverse myelitis, chorea, aseptic meningitis | Peripheral neuropathy, cranial neuropathies | ANA, anti-dsDNA; antiphospholipid antibodies (anticardiolipin, β2-GP1, lupus anticoagulant) | Steroids + cyclophosphamide (severe); anticoagulation for APS |
| Sjögren syndrome | Myelitis (can mimic NMOSD — check AQP4), cognitive dysfunction, CNS lymphoma risk | Sensory neuropathy (small fiber or sensory ganglionopathy), trigeminal neuropathy | Anti-SSA (Ro), anti-SSB (La); lip biopsy; Schirmer test | Steroids, rituximab; treat neuropathy symptomatically |
| IgG4-related disease | Orbital pseudotumor (most common neuro), hypertrophic pachymeningitis, hypophysitis, perineural disease | Cranial nerve palsies | ↑ Serum IgG4; biopsy: storiform fibrosis, >10 IgG4+ plasma cells/HPF | Steroids (very responsive); rituximab for refractory |
💎 Board Pearl
Neurosarcoidosis: facial nerve palsy is the most common cranial neuropathy; can be bilateral. Serum ACE is neither sensitive nor specific — do not use to rule in or out. Non-caseating granulomas = gold standard finding. Infliximab (NOT etanercept) for refractory neurosarcoidosis — etanercept can paradoxically worsen sarcoidosis. Bilateral facial palsy differential: sarcoidosis, Lyme, GBS, HIV, lymphoma.CNS Vasculitis — PACNS vs RCVS vs Susac
| Feature | PACNS | RCVS | Susac Syndrome |
|---|---|---|---|
| Presentation | Insidious: headache, cognitive decline, strokes in multiple territories | Acute: recurrent thunderclap headaches over days to weeks | Subacute: encephalopathy + vision loss + hearing loss |
| Headache pattern | Chronic, progressive, dull | Thunderclap (<60 seconds to peak); recurrent; often triggered by Valsalva, exertion, sex | Variable; may be mild or absent |
| Imaging | Multifocal infarcts in different vascular territories; white matter lesions; mass-like lesions possible | Convexity SAH; posterior predominant edema (like PRES); infarcts if severe | Snowball lesions in CENTRAL corpus callosum (pathognomonic); periventricular white matter lesions |
| Angiography | Beading/stenosis (~60% sensitivity); can be normal (small vessel) | Diffuse segmental vasoconstriction (beading); REVERSIBLE within 12 weeks | Branch retinal artery occlusions on fluorescein angiography |
| CSF | Elevated protein, pleocytosis in ~90%; ESR/CRP often NORMAL | Usually NORMAL | Elevated protein, mild pleocytosis possible |
| Biopsy | Gold standard (leptomeninges + cortex); 25% false-negative rate | Not indicated | Not indicated |
| Treatment | Cyclophosphamide + corticosteroids induction; AZA/MMF maintenance | Calcium channel blockers (nimodipine/verapamil); remove triggers; NO immunosuppression | Aggressive: IVMP + IVIg + PLEX; MMF/AZA maintenance; antiplatelet |
| Prognosis | Chronic, relapsing; can be fatal without treatment | Self-limited (resolves in 1–3 months); generally good | Variable; early aggressive treatment improves outcomes |
💎 Board Pearl
RCVS = thunderclap headache + reversible vasoconstriction (resolves in 3 months); triggers include triptans, SSRIs, cannabis, postpartum. Do NOT immunosuppress RCVS — it is NOT a vasculitis. Susac = encephalopathy + BRAO + sensorineural hearing loss (clinical triad). Susac snowball lesions are in the CENTRAL corpus callosum; MS lesions are at the callosal-septal interface (Dawson fingers). PACNS brain biopsy: need leptomeninges + cortex in sample; 25% false-negative rate.Other Neuroimmunology Conditions
| Condition | Key Features | Diagnosis | Treatment |
|---|---|---|---|
| ADEM | Monophasic; children >> adults; post-infectious/post-vaccination; encephalopathy REQUIRED; large fluffy bilateral WM lesions + deep gray matter (thalamus) | Clinical: polyfocal deficits + encephalopathy + large lesions; MOG-IgG positive in many pediatric cases; OCBs usually absent | IV methylprednisolone → PO taper; IVIg or PLEX if refractory |
| Transverse myelitis | Acute/subacute bilateral motor + sensory + autonomic spinal cord dysfunction; sensory level; urinary retention | Spinal MRI (T2 hyperintensity ≥2 segments for idiopathic); CSF pleocytosis; rule out compressive, NMOSD, MS, MOG | IV methylprednisolone; PLEX if refractory; address underlying cause |
| NMOSD-associated ON | Severe, often bilateral; posterior > anterior; poor recovery; chiasmal involvement; AQP4+ | AQP4-IgG serum; MRI orbits (long-segment enhancement, often posterior/chiasmal) | IV methylprednisolone + early PLEX; long-term: rituximab/eculizumab/satralizumab/inebilizumab |
| Stiff-person syndrome | Progressive axial rigidity + painful spasms (triggered by startle/emotion); exaggerated lumbar lordosis; anti-GAD65 (very high titers >10,000) | Anti-GAD65 (high titer); anti-amphiphysin (if paraneoplastic → breast/SCLC); EMG: continuous motor unit activity at rest | Diazepam/baclofen (symptomatic); IVIg (immunotherapy of choice); rituximab; tumor treatment if paraneoplastic |
| Hashimoto encephalopathy (SREAT) | Subacute encephalopathy (cognitive decline, seizures, myoclonus, stroke-like episodes); anti-TPO/anti-TG antibodies; DRAMATICALLY steroid-responsive | Diagnosis of exclusion; elevated anti-TPO/anti-TG; EEG: diffuse slowing; CSF: elevated protein; normal thyroid function often | High-dose corticosteroids (dramatic response = diagnostic clue); steroid-sparing agents if relapsing |
| Immune checkpoint neurotoxicity | Anti-PD-1/PD-L1/CTLA-4 therapy; myasthenia gravis (most common NMJ), GBS, encephalitis, myositis, aseptic meningitis, transverse myelitis; can overlap (myasthenia + myositis + myocarditis) | Temporal relationship to checkpoint inhibitor; antibody testing; EMG/NCS; MRI | Hold checkpoint inhibitor; high-dose steroids; IVIg or PLEX for severe; permanent discontinuation for grade 3–4 |
| CLIPPERS | Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids; ataxia, diplopia, dysarthria; punctate/curvilinear Gd-enhancing lesions in pons → "peppering" pattern | MRI: punctate gadolinium-enhancing lesions centered on pons; biopsy: perivascular T-cell infiltration; exclude lymphoma | Corticosteroids (dramatic response); steroid-sparing (MTX, MMF); relapses on taper common |
| Bickerstaff brainstem encephalitis | Ophthalmoplegia + ataxia + encephalopathy (altered consciousness); overlap with GBS and Miller Fisher; anti-GQ1b antibodies | Anti-GQ1b (positive in ~65%); CSF albuminocytologic dissociation; MRI brainstem lesions possible; EEG: diffuse slowing | IVIg or PLEX (as for GBS); generally good prognosis |
Clinical Pearl
ADEM = monophasic, children, post-infectious, large fluffy lesions, encephalopathy REQUIRED for diagnosis. If "ADEM" recurs, think MOGAD or MS. Multiphasic ADEM = second event ≥3 months after first; if ≥2 non-ADEM events → likely MOGAD or MS. SREAT (Hashimoto encephalopathy) is a diagnosis of exclusion — the dramatic steroid response is the diagnostic clue. Checkpoint inhibitor neurotoxicity: watch for MG + myositis + myocarditis overlap (can be fatal).Key Numbers & Board Traps
| Fact | Value / Detail |
|---|---|
| McDonald DIS requirement | ≥1 T2 lesion in ≥2 of 4 regions (periventricular, cortical/juxtacortical, infratentorial, spinal) |
| OCB bands needed | ≥2 CSF-specific oligoclonal bands (not matched in serum) |
| MS relapse definition | Symptoms lasting ≥24 hours, occurring ≥30 days after previous attack, not explained by fever/infection |
| JCV index threshold | Anti-JCV Ab index >1.5 = high PML risk on natalizumab |
| Natalizumab PML risk factors | JCV Ab+ (index >1.5) + prior immunosuppression + duration >2 years → ~13/1000 |
| NMOSD LETM definition | ≥3 contiguous vertebral segments of T2 signal on spinal MRI |
| AQP4-IgG sensitivity in NMOSD | ~80% by cell-based assay; lower by ELISA (~70%); seronegative NMOSD exists |
| NMDAR encephalitis F:M ratio | ~4:1 overall; higher in teratoma-associated (nearly all female) |
| Rituximab redosing interval | Every 6 months; monitor CD19/CD20 counts for B-cell reconstitution |
| MS pregnancy relapse pattern | Relapses ↓ in 3rd trimester; ↑↑ rebound in first 3 months postpartum |
| Fingolimod first-dose monitoring | 6-hour continuous cardiac monitoring (ECG + BP); risk of bradycardia/AV block; do not use if resting HR <55 |
| Siponimod CYP2C9 genotyping | *3/*3 = contraindicated; required before starting |
| Alemtuzumab monitoring duration | Monthly CBC + TFTs + urinalysis for 4 years after LAST dose |
| Teriflunomide washout | Cholestyramine 8 g TID ×11 days; confirm levels <0.02 mg/L ×2 (two weeks apart) before conception |
| DMF ALC threshold for PML | Stop if ALC <500 for >6 months |
| Anti-GAD65 titer threshold | Low (<20) = type 1 DM; very high (>10,000) = neurological (SPS, ataxia, epilepsy) |
| PPMS progression requirement | ≥1 year of progressive disability (not a single time point) |
| CIS conversion risk with OCBs | OCBs + ≥2 T2 lesions = ~90% convert to MS within 20 years |
| Eculizumab meningococcal vaccine | Must vaccinate ≥2 weeks before first dose; if urgent, start antibiotics until 2 weeks post-vaccine |
| PACNS biopsy false-negative rate | ~25% (sampling error); need leptomeninges + cortex in specimen |
| RCVS resolution | Vasoconstriction resolves within 1–3 months (by definition) |
💎 Board Pearl
NMOSD + MS DMTs = disaster (interferons, fingolimod, natalizumab can worsen NMOSD). PML is not just natalizumab (also DMF, fingolimod, rituximab). FBDS are NOT epilepsy — they respond to immunotherapy, not AEDs. Etanercept can paradoxically worsen sarcoidosis (use infliximab). GCA + vision loss = start steroids BEFORE biopsy. Anti-NMDAR encephalitis can follow HSV encephalitis. Teriflunomide + pregnancy = cholestyramine washout required. IVIg + IgA deficiency = anaphylaxis risk. ADEM requires encephalopathy — if absent, it is not ADEM.