Acute disseminated encephalomyelitis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

ADEM produces multifocal inflammatory demyelination after immune activation, commonly one to three weeks after a nonspecific infection. Headache, fever, vomiting and meningism may precede encephalopathy, pyramidal weakness, ataxia, cranial neuropathy, optic neuritis, myelitis or seizures. Younger children may present with irritability or developmental regression rather than a clearly articulated cognitive complaint. Adult ADEM is rarer and deserves particularly careful exclusion of infection, malignancy, vasculitis and first-presentation MS.

MRI is central but evolves with time. Lesions are often bilateral and asymmetric, large and hazy, with deep grey involvement; enhancement varies because lesions arise around a similar period. Spinal lesions can be extensive. CSF may show mild lymphocytosis or protein elevation, while persistent CSF-restricted oligoclonal bands make classic monophasic ADEM less typical. No single scan pattern or biomarker is pathognomonic, and radiology must be read with the encephalopathic polyfocal syndrome.

Acute treatment suppresses inflammation while supportive care prevents secondary injury from seizure, aspiration, immobility, pressure, bladder dysfunction and poor nutrition. Recovery can appear rapid after corticosteroid but continue for months. MOG-positive children may relapse with optic neuritis or another demyelinating phenotype, so follow-up should include a planned diagnostic review rather than an unqualified promise that recurrence cannot happen.

Key points

ADEM is an acute inflammatory demyelinating disorder that is commonest in children and often follows an infection; it is much less commonly the first diagnosis in an adult.
Encephalopathy is a defining clinical feature: altered behaviour, irritability, drowsiness or reduced consciousness accompanies polyfocal neurological deficits.
MRI usually shows large, bilateral, poorly demarcated T2 or FLAIR lesions in subcortical and central white matter, deep grey nuclei, brainstem, cerebellum or spinal cord.
A preceding fever or viral illness does not prove ADEM, and active infectious encephalitis must be covered and investigated until sufficiently excluded.
MOG-IgG is found in an important subgroup, especially children, and may predict optic neuritis, extensive myelitis or recurrence requiring a revised MOG-associated disease diagnosis.
Typical MS more often lacks encephalopathy and shows small well-demarcated periventricular, juxtacortical or infratentorial lesions with dissemination in time.
First-line treatment for a significant attack is commonly high-dose intravenous methylprednisolone; IV immunoglobulin or plasma exchange is used for severe inadequate response under specialist protocols.
Most children improve substantially, but cognition, behaviour, fatigue, seizures, vision, movement and school participation require deliberate follow-up.
New events after the expected monophasic period demand expert reconsideration of MOGAD, MS, NMOSD, recurrent ADEM, infection or a genetic or metabolic mimic.
Vaccination history should be recorded without implying causation: infections are common antecedents and temporal association alone is not evidence that a vaccine caused the illness.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Post-infectious immune activation

ADEM commonly follows a non-specific infection, particularly in children. The temporal association supports immune activation but does not identify the organism or remove the need to exclude active infection.

MOG-associated inflammation

MOG immunoglobulin is present in an important subgroup and can accompany extensive myelitis or optic neuritis; recurrence may require reclassification as MOG-associated disease.

Idiopathic inflammatory disease

Some cases have no identifiable trigger or antibody. Adult presentations require especially careful exclusion of infection, malignancy, vasculitis and a first demyelinating event from another disorder.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Peripheral immune activation
An antecedent immune stimulus generates lymphocyte and antibody responses that become directed against central nervous-system myelin or associated antigens in a susceptible person.
2
Blood–brain barrier inflammation
Activated immune cells enter the central nervous system, producing multifocal perivenous inflammation, oedema and broad areas of demyelination across white matter, deep grey structures, brainstem or cord.
3
Distributed conduction failure
Loss of myelin and tissue swelling disrupts several neural networks simultaneously, creating encephalopathy with polyfocal weakness, ataxia, cranial neuropathy, optic neuritis, myelitis or seizures.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Post-infectious encephalopathyRed flag

Days to weeks after a febrile illness, a child becomes unusually irritable, confused or sleepy and develops multifocal weakness, ataxia, cranial-nerve findings or seizures.

Polyfocal demyelinationRed flag

Deficits cannot be explained by one small lesion: combinations include hemiparesis, bilateral pyramidal signs, optic symptoms, cerebellar ataxia, brainstem dysfunction and an inflammatory cord syndrome.

Raised pressure or severe oedemaRed flag

Headache, repeated vomiting, papilloedema, hypertension with bradycardia, abnormal posturing or falling consciousness suggests life-threatening swelling and requires neurocritical escalation.

MS-leaning evolution

No encephalopathy, typical small ovoid periventricular lesions, new silent lesions on follow-up or a later anatomically separate event raises MS rather than monophasic ADEM.

MOG-associated course

Bilateral optic-disc swelling, severe optic neuritis, longitudinal myelitis, cortical encephalitis or recurrent attacks should prompt correctly timed serum MOG-IgG testing and phenotype review.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
MRI brain with gadoliniumFirst step
Why
Demonstrate the distribution and age of demyelinating lesions while excluding tumour, abscess, stroke, PRES and other structural encephalopathies.
Interpretation and limitations
Large bilateral poorly marginated white-matter lesions with basal-ganglia, thalamic, brainstem or cerebellar involvement support ADEM. Normal or equivocal early imaging may warrant expert review and repeat scanning.
02
MRI whole spine and orbits when indicated
Why
Define associated myelitis or optic neuritis and exclude spinal compression in patients with cord signs.
Interpretation and limitations
Extensive cord disease or optic-nerve enhancement affects acute monitoring and the differential, particularly MOGAD and AQP4-NMOSD; imaging phenotype is not antibody status.
03
Lumbar puncture after safety assessment
Why
Investigate infection and inflammatory alternatives and provide paired testing where immune demyelination is suspected.
Interpretation and limitations
Send cells, protein, glucose, cultures and viral PCR selected to context, plus oligoclonal bands. Mild inflammation is compatible; profound hypoglycorrhachia or marked neutrophilia should redirect urgently.
04
Serum MOG-IgG and AQP4-IgG
Why
Identify antibody-associated demyelination that changes recurrence counselling and longer-term specialist management.
Interpretation and limitations
Use validated cell-based assays and interpret titre, timing and phenotype. Repeat MOG testing may be considered by specialists because persistence can carry different implications from transient positivity.
05
EEG and acute physiology
Why
Detect non-convulsive seizure activity and quantify systemic or neurological deterioration during encephalopathy.
Interpretation and limitations
Generalised or focal slowing is nonspecific, while epileptiform activity directs antiseizure care. Monitor glucose, sodium, ventilation and intracranial-pressure features rather than attributing all reduced consciousness to demyelination.
06
Follow-up MRI and developmental assessment
Why
Confirm radiological resolution or stability and detect new lesions, cognitive sequelae or diagnostic evolution.
Interpretation and limitations
Resolution supports ADEM; new lesions separated in time require specialist reconsideration. School reports, neuropsychology and functional measures can reveal important deficits despite a normal motor examination.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Infectious encephalitis

Fever, seizures and encephalopathy overlap closely; cerebrospinal-fluid microbiology, imaging and clinical evolution guide distinction, while empirical antimicrobial treatment continues until infection is sufficiently excluded.

Multiple sclerosis

MS more often lacks encephalopathy and shows smaller, sharply defined lesions disseminated in characteristic locations and time; persistent cerebrospinal-fluid-restricted oligoclonal bands also make classic ADEM less typical.

MOG-associated disease or NMOSD

Severe bilateral optic neuritis, longitudinally extensive myelitis, area-postrema symptoms or recurrent attacks favour an antibody-associated disorder and require serum cell-based testing and specialist review.

Vasculitis, tumour or metabolic disease

Adult onset, progressive rather than monophasic evolution, systemic inflammation, atypical enhancement or a discordant metabolic phenotype should broaden investigation beyond inflammatory demyelination.

Additional chapter-specific clues

Infectious mimicRed flag

Fever, meningism, focal temporal seizures, rash, immunosuppression or travel and exposure risk sustain concern for viral, bacterial or other infection despite demyelinating MRI lesions.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Initial encephalopathyCover dangerous alternativesFirst stepA child or adult has altered consciousness or behaviour with multifocal neurological signs.

1EscalationStabilise airway, breathing and circulation, check glucose and electrolytes, treat seizures promptly and escalate signs of cerebral oedema or respiratory weakness to paediatric or adult critical care.
2Obtain urgent MRI and, when safe, CSF for microbiology and inflammation; give empiric aciclovir and antibacterial cover according to the encephalitis or meningitis pathway while infection remains credible.
3Document the preceding illness, medicines, vaccination timing, toxic exposures, immune status and detailed neurological pattern without assuming that temporal association supplies causation.
4Discuss early with a neuroinflammatory specialist and neuroradiologist because adult disease, atypical imaging or rapid worsening broadens the differential substantially.

02Demyelinating attackSuppress inflammation and prevent secondary harmThe clinicoradiological picture supports ADEM and untreated infection or structural disease is no longer the dominant concern.

1Administer high-dose intravenous methylprednisolone, commonly 20 to 30 mg/kg daily up to 1 g for three to five days in paediatric specialist protocols, with an adult regimen determined locally.
2Use a planned oral taper when the treating specialist judges it necessary, monitoring behaviour, sleep, blood pressure, glucose, gastric risk and intercurrent infection.
3EscalationEscalate severe or steroid-incomplete disease to IV immunoglobulin or therapeutic plasma exchange through the tertiary service, considering haemodynamics, access and concurrent medicines.
4Manage swallowing, nutrition, bladder, bowel, skin, thrombosis, pain and seizures while physiotherapy, occupational and speech-and-language assessment begin.

03Longitudinal reviewConfirm monophasic recoveryThe acute episode has improved and discharge or transfer to rehabilitation is planned.

1Record a detailed cognitive, behavioural, visual, motor and school or work baseline, then provide goal-led neurorehabilitation and a named route back to the neurology team.
2Review MOG, AQP4, CSF and imaging results and arrange repeat MRI at a specialist-defined interval to ensure lesions resolve and no dissemination in time appears.
3Reassess urgently if optic pain, new visual loss, weakness, ataxia, seizure or encephalopathy recurs; revise the diagnosis before committing to long-term immunotherapy.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

Reduces acute CNS inflammation once ADEM is the working diagnosis and serious infection is covered or excluded.

Intravenous methylprednisolone

Adults commonly receive 1 g daily for three to five days; paediatric dosing is weight-based and specialist-led.

Monitor glucose, blood pressure, electrolytes, mood, sleep, gastrointestinal risk and infection; paediatric dose caps and any oral taper follow the tertiary protocol.

Provides rescue immunomodulation when response to corticosteroid is inadequate or plasma exchange is less suitable.

Intravenous immunoglobulin

A specialist course commonly totals 2 g/kg divided over two to five days.

Review renal function, fluid tolerance, thrombosis, haemolysis, headache and immunoglobulin A-related reaction risk, using actual product guidance and infusion policy.

May rescue fulminant, life-threatening or steroid-refractory demyelination by removing circulating inflammatory factors.

Therapeutic plasma exchange

The apheresis team determines exchange volume and commonly schedules five to seven treatments.

Vascular access, haemodynamic instability, hypocalcaemia, fibrinogen depletion, sepsis and removal of other therapies need specialist sequencing.

Protects against treatable herpes encephalitis during the early period of diagnostic uncertainty.

Intravenous aciclovir

Use age, weight and renal-adjusted local encephalitis dosing until HSV is adequately excluded.

Maintain appropriate hydration, follow renal function and review PCR timing; crystal nephropathy and neurotoxicity are more likely with accumulation.

Treats clinical or electrographic seizures that can compound cerebral injury and obscure assessment.

Antiseizure medicine

Select and load according to the acute seizure protocol, age, organ function and EEG findings.

Avoid unnecessary long-term continuation after an acute symptomatic seizure without neurology review; sedation, behaviour, rash, liver effects and reproductive counselling vary by agent.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Seizures and cerebral oedema

Diffuse inflammatory injury can provoke recurrent seizures, reduced consciousness and raised intracranial pressure, sometimes requiring airway support, critical care and treatment of secondary brain injury.

Motor, visual and bulbar disability

Myelitis, optic-nerve involvement and brainstem lesions may leave weakness, impaired mobility, visual loss, dysphagia or bladder dysfunction despite control of acute inflammation.

Cognitive and behavioural sequelae

Attention, memory, behaviour, fatigue and educational participation may remain impaired after apparent motor recovery, making neuropsychological and school or workplace follow-up important.

Relapse and diagnostic revision

A new demyelinating event after the expected monophasic course can reveal MOG-associated disease, multiple sclerosis or NMOSD, changing counselling and long-term relapse-prevention decisions.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Use serial Glasgow Coma Scale or age-appropriate consciousness assessment, pupils, focal examination and vital signs to detect seizure, swelling or brainstem deterioration.
Monitor blood pressure, glucose, electrolytes, renal function and infection markers during corticosteroid, aciclovir and rescue immune treatment.
Track seizure burden clinically and with EEG when consciousness or abnormal movements remain unexplained; review the need for antiseizure treatment after the acute phase.
Assess swallowing, nutrition, bladder and bowel function, skin, mobility, vision and communication throughout admission instead of waiting for consciousness to fully recover.
At follow-up, ask about fatigue, attention, processing speed, behaviour, mood, sleep and school or occupational performance, even if strength and gait appear normal.
Arrange urgent reassessment for any new encephalopathy, seizure, optic symptoms, sensory level or motor deficit, since recurrence changes both diagnosis and prevention strategy.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Encephalopathy distinguishes ADEM

Multifocal deficits without altered behaviour or consciousness should prompt a different demyelinating label rather than stretching the ADEM definition.

Grey matter may be involved

Thalamic and basal-ganglia lesions can accompany white-matter abnormalities, a pattern that is often more supportive than classic small MS-type plaques.

MOG changes the horizon

MOG positivity may accompany a typical first ADEM attack but persistent antibody or later optic and cord events can redefine the long-term disorder.

Children hide cognition

Irritability, lost skills, poor concentration or reduced school stamina may be the practical expression of encephalopathy and post-acute injury.

Radiology can lag

Clinical disease may precede fully evolved lesions, so a high-quality repeat MRI is reasonable when initial imaging and objective findings disagree.

Monophasic is retrospective

The expected one-off course can only be confirmed with time; counselling should be optimistic but include clear relapse safety-netting.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing ADEM from an infection followed by weakness when there is no encephalopathy or supportive multifocal imaging.
02
Withholding empiric antiviral therapy solely because the first MRI looks demyelinating.
03
Calling large bilateral lesions multiple sclerosis without considering age, encephalopathy, deep-grey involvement and lesion margins.
04
Using a positive MOG result without titre, assay method or compatible phenotype to bypass clinical reasoning.
05
Ignoring cognition and school performance because motor recovery appears complete.
06
Starting indefinite immunosuppression after one improving event without defining recurrence risk or a relapsing diagnosis.