Today, I review, link to, and excerpt from The Cribsiders‘ #166: DEMystifying ADEM.*

*Venkataraman  V, Arellano J, Berk J, Chiu C, Masur S. “166 DEMystifying ADEM”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ Jan 28, 2025.

All that follows is from the above resource.

In this episode, Dr. Janetta Arellano (Children’s hospital of Orange County) joins us to take a deep dive into ADEM. We discuss the key features, diagnostic approach, and management of ADEM, with important pearls for distinguishing it from other neurologic emergencies.

Acute Disseminated Encephalomyelitis (ADEM) Pearls

1. For patients coming in with acute neurological symptoms prompt neuroimaging (MRI preferred) will help narrow our differential diagnosis
2. Prompt diagnosis and early treatment of ADEM will help prevent relapses and improve outcomes
3. Even in the outpatient setting, always keep an open mind about other diagnoses especially if the course deviates from expected recovery.

ADEM Notes 

Pathophysiology 

Acute Disseminated Encephalomyelitis is an autoimmune demyelinating disease of the central nervous symptom, occurring most commonly after a viral infection, presenting with multifocal neurologic deficits and encephalopathy.

1. Triggering Event – Viral Infection triggers immune response against the antigen to the infection itself
2. Molecular Mimicry – Antigen can share structural similarities to myelin protein and the immune system cross-reacts with the CNS myelin
3. Immune Activation – T-cells infiltrate the CNS resulting in cytokine release and B-cells producing antibodies leading to inflammation and demyelination

Immune Based Demyelinating Disorder Breakdown 

	Multiple Sclerosis	Myelin Oligodendrocyte Glycoprotein Associated Disease (MOGAD)	Neuromyelitis Optica Spectrum Disorder (NMOSD)
Clinical course	Relapsing/Remitting	Monophasic most common	Relapsing most common
Pathogenic Antibody	N/A	Anti-MOG IgG	AQP4-IgG
Clinical Presentation/Diseases	Optic Neuritis, Myelitis, Cerebellar symptoms	Optic Neuritis Transverse Myelitis ADEM Neuromyelitis Optica Cerebral Cortical Encephalitis	Neuromyelitis Optica Transverse Myelitis

Presentation

Encephalopathy is required for diagnosis of ADEM – can range from irritability, confusion, Level of consciousness changes. This can also be presented with ataxia and autonomic symptoms as well. (Hardy et.al., 2016)

Differential Diagnosis

Presentation is similar to other concerning neurological conditions that need to be further assessed and ruled out

• CNS infection (encephalitis/meningitis)
• Increased ICP
• Vascular – stroke or vasculitis
• Other autoimmune demyelinating diseases (see above)
• Malignancy

Work-up

Further Physical Exam Findings

• Vital signs – Fever, Signs of Dysautonomia, Vital signs suggestive of Increased ICP (Hypertension, Bradycardia)
• Mental Status changes
• Meningeal Signs – Neck stiffness, positive Kernig, Brudzinski sign
• Focal neurologic deficits on thorough neurological exam
• Gait Disturbance – Is there weakness, ataxia
• Cerebellar signs and symptoms

Investigations 

MRI Brain (and spine depending on the patient) with and without contrast is ideal – can be challenging in younger kids who require sedation. While waiting for this, can prioritize CT head non-contrast.

Findings for ADEM on MRI: Bilateral T2 Flair hyperintensity in white and grey matter.

Serum Studies include:

• CBC
• Electrolytes
• Inflammatory markers (ESR, CRP, PCT)
• Anti-MOG IgG – for more confirmatory testing for ADEM by MOGAD

CSF studies from High Volume Lumbar puncture (15-20 cc):

• Opening and closing pressure
• Cell count with differential
• Protein
• Glucose
• CSF culture
• Meningoencephalitis panel (PCR of multiple organisms)
• Oligoclonal bands

In ADEM, there may be a mild lymphocytic predominance on cell count and mild protein elevation on CSF.

Diagnostic Criteria for ADEM
As per the International Pediatric Multiple Sclerosis Study Group (IPMSSG) the diagnostic criteria for ADEM includes:

• First polyfocal CNS event – multifocal neurological changes
• Encephalopathy not explained by fever or metabolic issues
• Large poorly demarcated T2 lesions primarily in the white matter
• No previous MRI findings (Monophasic) (Krupp et. al., 2013)

Treatment

First line treatment: High dose corticosteroids – Methylprednisolone 30mg/kg max 1g for 3-5 days
Improvement is based on clinical symptoms – Repeat neuroimaging early on may not be helpful.

After an inpatient steroid course, patients are sent home on steroid taper to prevent recurrence of symptoms.

General taper: 2mg/kg/day with max of 60mg per day, and start weaning weekly for a total of 4 weeks.

Second line treatment:

• IVIG – if no improvement on corticosteroids or contraindication to steroid use
• Plasma exchange – if very serious disease – on a ventilator in the ICU. This results in more immediate response.

Disparities in Care 

• Disparities in access to care – Rural or underserved populations with no children’s hospitals, pediatric neurologists or neuroimaging requiring sedation.
• Language Barriers – limited English proficiency and gaps even when using interpreter systems.
• Provider level of comfort – generally less common so symptoms are usually attributed to infections, toxins, or psychiatric diagnoses leading to delays.

Prognosis

Prognosis with treatment is good with prompt treatment. Most patients recover within weeks to months. 20% of patients may have mild residual deficits – attention issues, subtle motor deficits. Follow-up MRI 3-6 months later shows improvement or resolution of lesions.

Prognosis without treatment may lead to relapse, especially with the MOG positive treatments.

After discharge from the hospital, there should be a follow-up with the neurologist 4-6 weeks after discharge to monitor neurologic recovery, school performance. Can consider repeating MRI 3-6 months after treatment to assess improvement. If there is residual deficits, referring them to therapy.