What is the treatment for acute demyelinating encephalitis?

Treatment of Acute Demyelinating Encephalitis

Initiate high-dose intravenous methylprednisolone (1 g daily for 3-5 days) immediately after ruling out infection, followed by an oral corticosteroid taper over 4-6 weeks. 1

Immediate Initial Management

Rule Out Infection First

• Start empirical intravenous acyclovir immediately while awaiting diagnostic confirmation, as herpes simplex encephalitis requires different treatment and cannot be missed 1, 2
• Continue acyclovir until CSF PCR results return negative for HSV 2
• Obtain urgent neurology consultation within 24 hours of presentation 3

Diagnostic Workup Before Definitive Treatment

• Perform lumbar puncture with CSF analysis including cell count, protein, glucose, viral PCRs (especially HSV and JCV), autoimmune encephalitis panel, oligoclonal bands, and CNS demyelinating disease antibodies (aquaporin-4 and myelin oligodendrocyte glycoprotein) 2, 1
• Obtain MRI with contrast of brain and spinal cord within 48 hours 2, 3
• Send serum paraneoplastic and autoimmune encephalitis panels 2

First-Line Immunotherapy

High-Dose Corticosteroids (Preferred Initial Treatment)

• Administer methylprednisolone 1 g IV daily for at least 3-5 days once infection is ruled out based on basic CSF results 1, 2, 4
• Alternative dosing for children: methylprednisolone 20-30 mg/kg/day (maximum 1 g/day) for 3-5 days 4
• Follow with oral corticosteroid taper over minimum 4-6 weeks to prevent symptom recurrence 1, 2, 4
• If symptoms flare during taper, extend the taper duration or temporarily increase the dose 1, 2

When to Use Alternative First-Line Agents

• Consider IVIG (2 g/kg divided over 2-5 days) or plasma exchange if corticosteroids are contraindicated or not preferred 2, 4
• IVIG is preferred first in agitated patients and those with bleeding disorders 2
• Plasma exchange is preferred first in patients with severe hyponatremia, high thromboembolic risk, or associated brain/spinal demyelination 2

Second-Line Therapies for Inadequate Response

Combination Therapy Approach

• If no clinical, radiological, or electrophysiological improvement by end of initial treatment cycle, add IVIG or plasma exchange 2
• If no improvement after 3 days of corticosteroids, proceed to IVIG (0.4 g/kg/day for 5 days) or plasmapheresis 2, 4
• Plasma exchange consists of 5-10 sessions every other day 2

Critical Timing Consideration

• Do not administer plasmapheresis immediately after IVIG, as it will remove the administered immunoglobulin 2

Severe Presentations Requiring Early Combination

• For severe initial presentations (severe dysautonomia, new onset refractory status epilepticus, rapidly declining consciousness), consider starting with combination therapy of steroids plus IVIG or steroids plus plasma exchange from the beginning rather than sequentially 2

Third-Line Therapies for Refractory Cases

When to Escalate

• If no clinical or radiological improvement 2-4 weeks after completion of combined acute therapy, consider second-line immunosuppressive agents 2

Agent Selection Based on Mechanism

• Consider rituximab in known or highly suspected antibody-mediated autoimmunity (e.g., NMDAR-antibody encephalitis, positive MOG antibodies) 2
• Consider cyclophosphamide in known or highly suspected cell-mediated autoimmunity (e.g., classical paraneoplastic syndrome) 2
• Novel approaches such as tocilizumab or bortezomib may be considered if conventional second-line therapies fail, though evidence is minimal 2

Severity-Based Treatment Algorithm

Grade 2 (Moderate): Some interference with ADLs

• Stop any immune checkpoint inhibitors if applicable 2
• Start prednisone 1 mg/kg daily and taper over 1 month 2
• Obtain neurology consultation 2

Grade 3-4 (Severe/Life-Threatening): Limiting self-care

• Permanently discontinue immune checkpoint inhibitors if applicable 2
• Admit patient for inpatient care (ICU level for Grade 4) 2
• Start methylprednisolone pulse dosing 1 g/day 2
• Consider IVIG or plasmapheresis if no improvement or symptoms worsen after 3 days 2
• Taper steroids over at least 4-6 weeks following acute management 2

Bridging and Maintenance Therapy

After Acute Phase

• Start bridging therapy with gradual oral prednisone taper, monthly intravenous immunoglobulin, or monthly intravenous methylprednisolone 2
• The minimum steroid taper duration is 4-6 weeks to prevent relapse 1, 2

Critical Pitfalls to Avoid

Do Not Delay Acyclovir

• Never delay empirical acyclovir while awaiting diagnostic confirmation, as HSV encephalitis requires immediate antiviral therapy and has devastating consequences if untreated 1, 2

Do Not Prematurely Discontinue Steroids

• Avoid steroid tapers shorter than 4-6 weeks, as premature discontinuation leads to symptom recurrence 1, 2
• Some patients demonstrate steroid-dependence and require extended tapers 1, 5

Do Not Forget Supportive Care

• Assess for airway protection and ventilatory support needs immediately in patients with declining consciousness 3
• Evaluate for urinary retention and constipation 2
• Obtain EEG to evaluate for subclinical seizures 2

Special Considerations

Autoimmune or Paraneoplastic Antibodies

• For patients with positive autoimmune encephalopathy or paraneoplastic antibodies, or those with limited improvement to standard therapy, consider rituximab in consultation with neurology 2

Tumor Screening

• Perform age-appropriate cancer screening including CT chest/abdomen/pelvis and testicular ultrasound in males, with consideration for mammogram/breast MRI, pelvic ultrasound, or whole body FDG-PET guided by clinical presentation and cancer risk factors 2