Acute Disseminated Encephalomyelitis

Domain

Practical Point

Definition

CNS demyelinating syndrome, almost always monophasic, typically postinfectious or post-vaccination.

Age

Mainly children; peak onset 3–7 years. M:F ≈ 1.8:1.

Trigger

Viral illness in 50–75% of pediatric cases. Post-vaccination <5% of cases.

Hallmark feature

Encephalopathy (obligatory) + polyfocal deficits.

Imaging

Large, poorly circumscribed, bilateral T2/FLAIR lesions in white AND grey matter; most enhance.

CSF

Lymphocytic pleocytosis, mildly ↑ protein; OCBs usually absent/transient.

Treatment

High-dose IV methylprednisolone → oral taper. Refractory: IVIG or plasma exchange.

Prognosis

Mostly favorable; mortality ~7.8%, residual deficits in ~47.5%.

Parameter

Detail

Annual incidence

0.07–0.60 per 100,000 individuals/year

Regional variation

Asia: 0.47–0.64/100,000 children (higher) vs Europe/US: 0.07–0.30/100,000 (lower)

Seasonality

More common in winter/spring, often after upper respiratory tract infection

Ethnic predisposition

None clearly identified

Factor

Detail

HLA associations

HLA-DRB1*1501, DRB1*1503, DQB1*0602, DRB1*01, DRB1*017(03) — linked to ADEM susceptibility

Post-transplant ADEM

Rare; reported after BMT, PBSCT, liver/renal transplant — thought to involve donor-antigen exposure or opportunistic infection

Paraneoplastic ADEM

Reported with multiple myeloma, small-cell lung carcinoma, hepatic epithelioid hemangioendothelioma

Other reported triggers

Folate deficiency, chronic cannabis abuse, herbal preparations (Echinacea, Aconitum, Adonis vernalis)

Category

Agents / Notes

Post-infectious — viral

Mumps, rubella, influenza, parainfluenza, HIV, dengue, Zika

Post-infectious — special mention

Chicken pox — high chance of cerebellar involvement

Post-infectious — bacterial

Mycoplasma pneumoniae (most common bacterial trigger), Borrelia burgdorferi, Leptospira

Post-vaccinal — mechanism

Aberrant immune response to vaccine components

Post-vaccinal — implicated vaccines

Old-generation rabies vaccine (Pasteur, spinal-cord derived), measles vaccine

Post-vaccinal — timing

Onset typically 8–21 days post-immunization; usually after the primary dose

Vaccine risk data

No significant increase in ADEM risk with most current vaccines; small excess risk noted with Tdap

Pathogen

Characteristic Features

HIV

Occurs during seroconversion or mild-moderate immunodeficiency; more aggressive, multiphasic course; atypical tumefactive/corpus callosum lesions

Dengue (DENV)

Rare (~0.4% of dengue patients); higher mortality than other viral triggers; worse outcome with higher admission fever

Measles (MV)

Historically high mortality; 25–40% of survivors develop permanent neurological sequelae

EBV

Linked to anti-MOG antibody induction → more severe MOG-positive ADEM; improves with rituximab (B-cell depletion)

SARS-CoV-2

~10% of neuro-COVID patients show ADEM/ADEM-like lesions; longer latency, worse recovery, more periventricular/corpus callosum involvement, less deep grey matter involvement

CMV

May progress to acute hemorrhagic leukoencephalitis if diagnosis delayed

HSV

Atypical presentations incl. transverse myelitis; marker of poor prognosis

VZV

Rare complication; associated with anti-MOG-positive ADEM

Mechanism

Detail

Molecular mimicry

Pathogen epitopes resemble myelin autoantigens — MOG, PLP, MBP, MOBP, OSP — triggering cross-reactive antibodies

Anti-MOG antibodies

Most common antibody; more frequent in younger patients; IgG1 subclass; ↑ relapse risk, earlier onset

BBB disruption

Direct CNS infection releases CNS-restricted autoantigens into systemic circulation → loss of self-tolerance

Acute phase cytokines

Th1 dominant — IL-1β, IL-6, IL-8, TNF-α, IFN-γ → lymphocyte migration across BBB

Remission phase cytokines

Shift to Th2 — IL-4, IL-10, TGF-β

Requirement

Detail

Core requirement

Encephalopathy — behavioral change or altered consciousness not explained by fever/postictal state (obligatory)

Plus

Polyfocal neurological deficits

Exclusions needed

No history of prior neurological disorder; must exclude viral/bacterial encephalitis

History to collect

Recent viral infection or vaccination

Timing rule

New/recurring symptoms within 3 months of onset = same initial event, not a relapse

Multiphasic ADEM defined as

A new qualifying episode occurring ≥3 months after the initial event

Phase

Features

Prodromal

Fever, headache, myalgia

Full-blown ADEM

Fever, encephalopathy (obligatory), seizures, quadriparesis/paraparesis, bilateral optic neuritis

Symptom

Frequency

Encephalopathy

100%

Fever

12–80%

Headache

6–64%

Bladder dysfunction

10–61%

Pyramidal signs

18–60%

Ataxia

36–53.5%

Seizures

18.5–50%

Cranial nerve dysfunction

6.6–45%

Optic neuritis

6.6–27%

Sensory disorders

0–17%

Feature

Detail

Modality

MRI brain with contrast

Lesion character

Large, fluffy, poorly circumscribed / blurred edges

Distribution

Involves grey AND white matter

Enhancement

Great majority of T2 lesions enhance → suggests recent onset, consistent with monophasic illness

Follow-up pattern

Partial resolution over weeks without new lesions appearing (unlike MS)

Feature

ADEM

MS

Single well-defined lesions

No

Yes

Perpendicular to corpus callosum

No

Yes

Black holes

No

Yes

Poorly circumscribed lesions

Yes

No

≥1 Gadolinium-enhancing lesion

No

Yes

Basal ganglia / thalamus involvement

Yes

No

Test

Finding

MRI brain with contrast

Large fluffy lesions, grey + white matter, contrast enhancing

CSF study

Lymphocytic pleocytosis, moderately increased protein count

VEP

Increased distal latency (optic nerve involvement)

EEG

Non-specific slowing; rules out non-convulsive status epilepticus

Method

Application

MRS (Cho/NAA ratio)

Distinguishes tumefactive demyelinating lesions from gliomas — high-grade gliomas show significantly higher Cho/NAA than TDLs

Machine learning (MRI radiomics)

Differentiates MOGAD ADEM-like presentation from classic ADEM using FLAIR features; accuracy >78.6%, AUC >89%

MOG-IgG + OCT + orbital imaging

MOG-IgG positive children (~71.1%) more often show optic nerve involvement and persistent MRI lesions vs MOG-IgG negative (lesions resolve completely in 75.5%)

Feature

ADEM

Tumefactive MS

Baló’s Concentric Sclerosis

Course

Usually monophasic

Chronic, relapsing

Monophasic or relapsing

MRI

Multiple lesions, no mass effect (except tumefactive ADEM)

Few large lesions, mass effect

Concentric ring lesions

CSF OCBs

Usually absent

Usually positive

Variable

Line

Regimen

Acute (first-line)

IV Methylprednisolone 1 g IV OD × 5 days (weight-based: 10–30 mg/kg/day, max 1000 mg/day)

Following steroids

Oral prednisone taper over 4–6 weeks

Refractory disease

Plasma exchange OR IVIG (2 g/kg over 2–5 days)

Fulminant / refractory raised ICP

Decompressive craniectomy (life-saving)

Steroid duration caution

Premature withdrawal (<3 weeks) → increased relapse risk

Term

Definition

Monophasic ADEM

Single episode; ~70–75% of cases

Multiphasic ADEM

New episode ≥3 months after initial event

MOG IgG disease

ADEM-like presentation; associated with higher relapse risk

ADEM-ON

Multiphasic variant with optic neuritis; usually anti-MOG positive

Parameter

Detail

Symptom onset

1–2 weeks post-infection; peak intensity over 4–7 days

Recovery

Most patients achieve substantial/complete recovery within weeks

Mortality

~7.8% overall

Residual deficits

~47.5% (worse outcomes in adults)

Fulminant variant

Acute Hemorrhagic Leukoencephalitis (Hurst disease) — hyperacute, necrotizing/hemorrhagic; ~47% mortality

Follow-up imaging

Recommended ~3 months post-acute event

Feature

Children

Adults

Fever

More common

Less common

Impaired consciousness

46–73%

20–56%

MRI lesion pattern

Thalamus, basal ganglia

Periventricular predominant

Gadolinium-enhancing lesions

~30%

55–60%

ICU admission / disease course

Less severe

More aggressive, higher ICU rates

Overall diagnostic clarity

IPMSSG criteria validated

No accepted adult criteria — >50% left undiagnosed