Other Neuroimmunology Topics

What You'll Learn

ADEM: monophasic post-infectious demyelination in children; encephalopathy is REQUIRED for diagnosis; large fluffy bilateral lesions with thalamic involvement; MOG-IgG+ in ~30–50% of pediatric cases. Lesions are typically of similar age; enhancement can be absent, patchy, or simultaneous. The key board contrast vs MS is recurrent non-encephalopathic attacks and lesions of different ages in MS
Transverse myelitis: short-segment + partial = MS; LETM + central = NMOSD; LETM + conus = MOGAD; always exclude compressive myelopathy first
Optic neuritis: MS = retrobulbar, unilateral, mild disc edema; NMOSD = severe, bilateral, poor recovery; MOGAD = anterior, bilateral, severe disc edema, perineural enhancement, good recovery
Stiff-person syndrome: anti-GAD65 antibodies; progressive axial stiffness + stimulus-triggered spasms; associated with type 1 DM and other autoimmune diseases; treat with benzodiazepines, baclofen, IVIg
Hashimoto encephalopathy (SREAT): steroid-responsive encephalopathy with anti-thyroid antibodies; diagnosis of exclusion; dramatic response to steroids
Immune checkpoint neurotoxicity: anti-PD-1/PD-L1/CTLA-4 therapy causes myasthenia gravis, encephalitis, GBS, myositis, hypophysitis; hold immunotherapy + high-dose steroids

HighYield Pearls

ADEM = encephalopathy REQUIRED: monophasic, post-infectious/post-vaccination, children > adults; large fluffy poorly-demarcated bilateral white-matter lesions with thalamic/basal-ganglia involvement; lesions are typically of similar age, but enhancement can be absent, patchy, or simultaneous (the key MS contrast is recurrent non-encephalopathic attacks + lesions of different ages in MS); OCBs usually NEGATIVE (vs MS); check MOG-IgG (positive in many pediatric ADEM → MOGAD spectrum); treat IV methylprednisolone, IVIG/PLEX if severe
Multiphasic ADEM (MDEM) vs MOGAD vs MS: second ADEM-like attack >3 mo later in same distribution = MDEM; further relapses → reclassify as MOGAD or MS (check MOG-IgG, OCBs)
Susac syndrome triad: subacute ENCEPHALOPATHY + BRANCH RETINAL ARTERY OCCLUSIONS + SENSORINEURAL HEARING LOSS; young women; “SNOWBALL” central callosal lesions on MRI; treat steroids + immunosuppression + antiplatelet/anticoagulant
CLIPPERS: chronic lymphocytic inflammation with PONTINE perivascular enhancement responsive to steroids; punctate/curvilinear “PEPPER-LIKE” enhancement in pons/brainstem; episodic ataxia + dysarthria + CN deficits; perivascular T-cell infiltrate on biopsy; chronic methotrexate/azathioprine after steroid taper
CRION: recurrent painful steroid-DEPENDENT optic neuritis with NO other CNS lesions; diagnosis of exclusion — rule out NMOSD, MOGAD, sarcoid, Susac; chronic immunosuppression required
Baló concentric sclerosis: MS variant with concentric “ONION-RING” alternating myelinated/demyelinated bands; often aggressive; steroids + PLEX
Marburg (acute fulminant MS): rapidly progressive weeks-to-months with extensive plaques + edema + mass effect; high mortality; aggressive immunosuppression + PLEX ± autologous HSCT
Tumefactive MS: >2 cm demyelinating lesion with INCOMPLETE RING enhancement (open toward gray matter), mass effect, but LESS diffusion restriction than abscess/tumor; Creutzfeldt-Peters cells on biopsy; steroids ± PLEX
Transverse myelitis — length matters: SHORT-segment (<3 segments) → MS, vascular, neuro-Behçet; LONGITUDINALLY EXTENSIVE (≥3 segments, LETM) → NMOSD, MOGAD, sarcoid, SLE/Sjögren, B12, dural AVF, HTLV-1; always exclude compressive cause first; workup AQP4 + MOG + ANA + Ro/La + ACE + B12 + HTLV-1 + LP (cells, protein, OCBs)
HAM/TSP: Caribbean/Japanese patient with slowly progressive spastic paraparesis + bladder dysfunction + sensory level; serum/CSF HTLV-1 antibodies confirm; no curative therapy — supportive + chronic steroids/IFN
Acute hemorrhagic leukoencephalitis (Hurst): hyperacute, severe ADEM variant with hemorrhage + necrosis + mass effect; often fatal; aggressive steroids + PLEX ± decompression

🔍 Quick ReferenceClinical · Imaging / pathology · Treatment / DDx

Clinical phenotype

Post-viral/post-vaccination encephalopathy + multifocal deficits in a child → ADEM
Encephalopathy + branch retinal artery occlusion + sensorineural hearing loss in young woman → Susac syndrome
Episodic ataxia, dysarthria, diplopia, steroid-responsive brainstem syndrome → CLIPPERS
Recurrent painful optic neuritis that always relapses on steroid taper, AQP4/MOG negative → CRION
Caribbean or Japanese adult with chronic spastic paraparesis + neurogenic bladder + sensory level → HAM/TSP (HTLV-1)
Rapidly progressive demyelination over weeks with extensive plaques and mass effect → Marburg variant of MS
Subacute hours-to-days bilateral motor/sensory level with sphincter dysfunction → Acute transverse myelitis
Child with ataxia after chickenpox/EBV, self-limited → Post-infectious cerebellitis

Imaging / pathology

Large, fluffy, poorly demarcated white-matter lesions with thalamic/BG involvement, typically of similar age (enhancement variable) → ADEM
Small punched-out central “SNOWBALL” corpus callosum lesions + microinfarcts → Susac syndrome
Punctate and curvilinear “peppering” (salt-and-pepper) perivascular enhancement in pons/brainstem → CLIPPERS
Concentric “onion-ring” alternating bands of myelinated and demyelinated tissue → Baló concentric sclerosis
Large >2 cm lesion with INCOMPLETE (open-ring) enhancement directed toward gray matter, mass effect, low diffusion restriction → Tumefactive MS
Ring-and-ball hemorrhages with fibrinoid necrosis of venule walls → Acute hemorrhagic leukoencephalitis (Hurst)
LETM ≥3 vertebral segments centrally located → NMOSD; LETM involving conus → MOGAD
Periodic high-amplitude EEG complexes + myoclonus + dementia in adolescent with prior measles → SSPE
Perivascular T-cell infiltrate on brainstem biopsy → CLIPPERS

Treatment / DDx

Steroid-DEPENDENT recurrent optic neuritis requiring chronic immunosuppression → CRION
Steroid-RESPONSIVE pontine encephalitis maintained on methotrexate or azathioprine → CLIPPERS
Aggressive demyelination requiring PLEX ± autologous HSCT → Marburg MS
IV methylprednisolone → oral taper, then IVIG/PLEX if refractory, in a child with post-viral encephalopathy → ADEM
Steroids + immunosuppression + antiplatelet/anticoagulation → Susac syndrome
Brain biopsy showing Creutzfeldt-Peters cells (reactive astrocytes with multiple nuclei) mimicking tumor → Tumefactive MS
No curative therapy; supportive + chronic mild steroids/IFN → HAM/TSP
Short partial TM with brain lesions and OCBs → MS; LETM with AQP4-IgG → NMOSD; LETM/ON with MOG-IgG → MOGAD; LETM with hilar adenopathy/elevated ACE → Neurosarcoidosis

ADEM (Acute Disseminated Encephalomyelitis)

Overview

Post-infectious or post-vaccination monophasic demyelinating disorder
Predominantly affects children (mean age 5–8 years); rare in adults
Typically follows a viral prodrome 1–4 weeks prior (measles, mumps, varicella, influenza, EBV, URI)
Pathophysiology: molecular mimicry → autoimmune attack on CNS myelin
Monophasic by definition — if relapses occur, reconsider MOGAD or MS

Clinical Features

Encephalopathy is REQUIRED (altered consciousness, behavioral change, confusion) — distinguishes ADEM from first MS episode
Multifocal neurological deficits: optic neuritis, hemiparesis, ataxia, cranial nerve palsies, seizures
Fever common at presentation
May present with LETM (longitudinally extensive transverse myelitis)

Diagnosis

MRI brain: large, fluffy, bilateral but asymmetric T2/FLAIR lesions; deep white matter, thalami, basal ganglia, brainstem; poorly demarcated
Thalamic involvement is characteristic of ADEM (rare in MS)
All lesions enhance simultaneously (same age) vs. MS lesions of different ages
CSF: lymphocytic pleocytosis, elevated protein; OCBs may be present but are transient (unlike MS where persistent)
MOG-IgG: positive in ~30–50% of pediatric ADEM; MOG+ relapsing disease → reclassify as MOGAD

ADEM vs MS

Feature	ADEM	MS
Age	Children (5–8 yr)	Young adults (20–40 yr)
Encephalopathy	Required	Absent
Course	Monophasic	Relapsing or progressive
MRI lesions	Large, fluffy, bilateral; thalami/BG	Periventricular Dawson fingers; well-demarcated
Enhancement	All lesions same age	Lesions of different ages (DIT)
OCBs	Transient	Persistent (>95%)
MOG-IgG	+ in ~30–50%	Typically negative

Treatment

First-line: IV methylprednisolone — pediatric: 20–30 mg/kg/day (max 1 g) × 3–5 days; adult: 1 g/day × 3–5 days — followed by oral taper over 4–6 weeks
Refractory: IVIg or PLEX
Prognosis: generally good; 70–90% recover fully or near-fully

Acute Hemorrhagic Leukoencephalitis (Hurst Disease)

Most severe form of ADEM — hyperacute, often fatal
Follows prodromal infection; rapid progression to coma over days
Pathology: perivascular demyelination with ring and ball hemorrhages, fibrinoid necrosis of venule walls
MRI: hemorrhagic white matter lesions with mass effect
Aggressive treatment with steroids, PLEX, decompressive surgery if needed

💎 Board Pearl

ADEM requires encephalopathy; MS does not — the single most important distinguishing feature
ADEM lesions are typically of similar age (enhancement can be absent, patchy, or simultaneous), whereas MS has lesions of different ages and recurrent non-encephalopathic attacks
If “ADEM” relapses → check MOG-IgG; MOG+ relapsing disease = MOGAD, not multiphasic ADEM
Thalamic involvement is characteristic of ADEM and rare in MS

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