What is the treatment for acute disseminated encephalitis (ADEM) in a patient of any age, possibly following a viral infection or vaccination?

Treatment of Acute Disseminated Encephalomyelitis (ADEM)

Start high-dose intravenous methylprednisolone 1 g daily (or 20-30 mg/kg/day in children, maximum 1 g) for 3-5 days, followed by an oral corticosteroid taper over 4-6 weeks minimum. 1, 2

Critical Initial Management

Begin empirical acyclovir immediately while awaiting diagnostic confirmation, as herpes simplex encephalitis requires urgent antiviral therapy and cannot be reliably distinguished from ADEM on initial presentation. 1, 3 This is a critical pitfall—delays in acyclovir beyond 48 hours worsen outcomes if HSV encephalitis is the actual diagnosis. 4

First-Line Corticosteroid Therapy

• Administer intravenous methylprednisolone 1 g daily for adults (or 20-30 mg/kg/day for children, maximum 1 g/day) for at least 3-5 days. 1, 2
• Follow with oral corticosteroid taper extending over 4-6 weeks minimum—this duration is essential to prevent symptom recurrence. 1, 2
• If symptoms flare during tapering, extend the taper duration or temporarily increase the dose rather than stopping abruptly. 1, 5

Common pitfall: Premature steroid discontinuation leads to relapse. The 4-6 week taper is not optional—shorter tapers frequently result in symptom recurrence. 1

Second-Line Therapies for Inadequate Response

If the patient shows poor response after 3 days of corticosteroids or has contraindications to steroids:

• Proceed to intravenous immunoglobulin (IVIG) 2 g/kg divided over 2-5 days as the next therapeutic option. 1, 2
• Alternatively, consider plasma exchange (plasmapheresis) for severe or life-threatening cases. 1, 2

Critical timing consideration: Do not perform plasmapheresis immediately after IVIG, as it will remove the administered immunoglobulin. 1 If both therapies are needed, perform plasmapheresis first or allow adequate time between treatments.

Severity-Based Treatment Algorithm

Moderate Cases

• Stop any immune checkpoint inhibitors if applicable. 1
• Initiate prednisone 1 mg/kg daily with taper over 1 month. 1

Severe Cases (Grade 3-4)

• Permanently discontinue immune checkpoint inhibitors if applicable. 1
• Admit for inpatient management with neurological specialist assessment within 24 hours. 3
• If no improvement or worsening after 3 days of high-dose corticosteroids, escalate to IVIG or plasmapheresis. 1
• Patients with falling consciousness require urgent ICU assessment for airway protection, ventilatory support, and management of raised intracranial pressure. 3

Third-Line Options for Refractory Cases

For patients with positive autoimmune encephalopathy antibodies (particularly MOG antibodies), paraneoplastic antibodies, or limited improvement with standard therapies:

• Consider rituximab in consultation with neurology—this represents a third-line option for refractory cases. 1
• MOG antibody testing may influence treatment decisions and prognosis, as MOG-antibody positive ADEM can have a relapsing course. 1, 6

Surgical Intervention

Decompressive craniectomy has been reported as a life-saving measure for ADEM patients with intractable intracranial hypertension. 2

Essential Diagnostic Workup During Treatment

While initiating treatment, obtain:

• MRI brain and spine (preferred over CT)—detects early cerebral changes in ~90% of cases versus only 25% for CT. 3
• CSF analysis with PCR results ideally available within 24-48 hours to guide antimicrobial discontinuation. 3
• Blood cultures and other infectious workup to exclude treatable infectious etiologies. 4
• Consider MOG antibody testing, as this influences prognosis and risk of relapse. 1

Common Pitfalls to Avoid

1. Never delay acyclovir while awaiting ADEM confirmation—HSV encephalitis is in the differential and requires immediate treatment. 1, 3
2. Avoid premature steroid discontinuation—the 4-6 week taper is critical; shorter courses lead to relapse. 1, 2
3. Do not perform plasmapheresis immediately after IVIG—timing matters for therapeutic efficacy. 1
4. Do not discharge without follow-up plans—sequelae including cognitive deficits, anxiety, and depression may not be immediately apparent. 3

Follow-Up and Rehabilitation

• All patients require assessment for rehabilitation, as neurological sequelae may emerge over time. 3
• Arrange outpatient neurology follow-up with plans for ongoing therapy before discharge. 3
• Monitor for relapse during and after steroid taper—some patients demonstrate steroid-dependence. 1, 5
• In children with relapsing demyelinating events, reconsider the diagnosis and evaluate for multiple sclerosis or neuromyelitis optica spectrum disorder. 2, 6