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) | Not eliminated as a concept — can be satisfied by additional biomarkers at the time of a single clinical/radiographic event | DIT can be met by: new T2/Gd+ lesion on follow-up MRI, simultaneous Gd+ and non-enhancing lesions, or biomarkers (OCBs, kappa FLC, ≥6 central vein sign lesions, or paramagnetic rim lesions) at the time of a single event |
| RIS (Radiologically Isolated Syndrome) | Qualifies as MS ONLY when DIS is met AND there is additional supportive evidence, with no clinical or radiographic alternative | Requires: DIS fulfilled + (DIT shown on serial MRI, OR ≥2 CSF-specific OCBs, OR ≥6 central vein sign lesions / paramagnetic rim lesions) + no better alternative diagnosis |
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 (same threshold as 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 can be substituted by biomarkers (OCBs, kappa FLC, ≥6 CVS lesions, PRL) at a single clinical/radiographic event — DIT is NOT eliminated as a concept, (3) RIS qualifies as MS ONLY when DIS is met AND additional supportive evidence is present (DIT on serial MRI, OR ≥2 CSF-specific OCBs, OR ≥6 CVS/PRL lesions), with no clinical or radiographic alternative. New supportive biomarkers: central vein sign (≥6 lesions or 40%+), paramagnetic rim lesions, and CSF kappa free light chains. Periventricular threshold remains ≥1 (same as 2017, NOT changed).Diagnostic Criteria & Antibody-Testing Scores
| Criterion / Score | Components | Threshold / Interpretation |
|---|---|---|
| APE2 score (Dubey 2017) Antibody Prevalence in Epilepsy and Encephalopathy | (1) New-onset refractory seizures, (2) autonomic dysfunction, (3) viral prodrome, (4) psychiatric features, (5) cognitive dysfunction, (6) temporal MRI changes, (7) CSF inflammation, (8) history of autoimmunity or cancer | Score ≥4 prompts neural antibody testing (sensitivity ~98%, specificity ~82%) |
| Graus 2016 — Possible Autoimmune Encephalitis | Subacute onset (<3 months) of working memory deficit, altered mental status, or psychiatric symptoms + ≥1 of: new focal CNS findings, seizures not explained by prior disorder, CSF pleocytosis (>5 WBC/µL), or MRI features suggestive of encephalitis | All criteria above + reasonable exclusion of alternative causes = Possible AE; upgrade to Definite when specific antibody identified or other criteria met |
| Graus 2021 PNS-Care Score Paraneoplastic Neurologic Syndromes | High-risk phenotypes: encephalomyelitis, limbic encephalitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus, sensory neuronopathy, LEMS High-risk antibodies: Hu, Yo, CV2/CRMP5, Ri, Ma2, amphiphysin, SOX1, KLHL11, DNER/Tr Scoring 0–10 across phenotype + antibody + cancer + follow-up domains | Definite PNS ≥8; Probable 6–7; Possible 4–5 |
| MOGAD 2023 Criteria | (1) Core clinical event (ON, myelitis, ADEM, cerebral monofocal/polyfocal deficit, brainstem/cerebellar syndrome, cortical encephalitis) + (2) MOG-IgG positive by cell-based assay (CBA) — clear positive serum titer typically >1:100, OR low/negative serum titer with supporting clinical/radiographic features + (3) exclusion of better diagnosis | Requires all three pillars; serum CBA preferred over fixed CBA or ELISA |
| IPND 2015 NMOSD Criteria | 6 core clinical characteristics: (1) optic neuritis, (2) acute myelitis, (3) area postrema syndrome (intractable hiccups/nausea/vomiting), (4) acute brainstem syndrome, (5) symptomatic narcolepsy or diencephalic syndrome with typical NMOSD MRI lesions, (6) symptomatic cerebral syndrome with typical NMOSD MRI lesions | AQP4-IgG positive: ≥1 core characteristic + exclusion of alternatives AQP4-IgG negative / unknown: ≥2 core characteristics meeting strict MRI requirements; ≥1 must be ON, LETM, or area postrema syndrome; dissemination in space required |
💎 Board Pearl
APE2 ≥4 = test for neural antibodies. Graus 2016 "Possible AE" is the entry-level umbrella criterion before subtype-specific antibodies define Definite. PNS-Care 2021 replaced the 2004 Graus criteria — uses a numeric score with high-risk phenotype + high-risk antibody + cancer + follow-up. MOGAD 2023: CBA is mandatory; ELISA-only positives are NOT acceptable. IPND 2015 NMOSD: AQP4− cases need stricter MRI criteria + ≥2 cores including ON, LETM, or area postrema.MS vs NMOSD vs MOGAD
| Feature | MS | NMOSD (AQP4+) | MOGAD |
|---|---|---|---|
| Antibody | None specific (OCBs in CSF) | AQP4-IgG (serum; 70–80% sensitivity by cell-based assay; lower by ELISA ~50–60%) | 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.Continue reading — sign in
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