What is the management protocol for a patient diagnosed with steroid autoimmune encephalopathy?

Management Protocol for Autoimmune Encephalitis

Initiate high-dose intravenous methylprednisolone (IVMP) immediately as first-line therapy once cerebrospinal fluid results exclude infection and primary CNS lymphoma or neurosarcoidosis are not considerations. 1, 2, 3

First-Line Immunotherapy

Corticosteroid Dosing

• Standard dosing: 1-2 mg/kg/day of IVMP 2, 3
• Pulse therapy for severe presentations: 1g daily for 3-5 days, particularly for severe NMDAR encephalitis, new-onset refractory status epilepticus (NORSE), or dysautonomia 4, 2, 3
• Corticosteroids are selected by 84% of experts for general autoimmune encephalitis presentations and 74% for faciobrachial dystonic seizures 4

When to Use IVIG or PLEX Instead of Steroids

Use IVIG (0.4 g/kg/day for 5 days) when: 1, 3

• Patient is agitated or combative
• Bleeding disorders or coagulopathy present
• Difficulty with central line placement
• Relative contraindications to steroids exist (uncontrolled hypertension, uncontrolled diabetes, acute peptic ulcer, severe behavioral symptoms that worsen with corticosteroids) 4

Use PLEX (5-10 sessions every other day) when: 1, 3

• Severe hyponatremia present
• High thromboembolic risk (known/suspected cancer, smoking, hypertension, diabetes, hyperlipidemia, hypercoagulable states) 4, 1
• Associated brain or spinal demyelination 1, 3

Combination First-Line Therapy

• For severe initial presentations, consider combining steroids plus IVIG or steroids plus PLEX from the beginning 1
• 19% of experts use corticosteroids combined with other agents for general autoimmune encephalitis presentations 4

Tumor Screening (Critical Step)

• Screen all young females with NMDAR encephalitis for ovarian teratoma using pelvic ultrasound or MRI, as surgical removal combined with immunotherapy significantly improves outcomes 2
• Perform CT chest/abdomen/pelvis with contrast for cancer screening in relevant cases 4

Second-Line Therapy

When to Escalate

• Add second-line agent if no meaningful clinical, radiological, or electrophysiological improvement after optimized first-line therapy for 2-4 weeks 1, 3
• 50% of experts add second-line agent only after failure of more than one first-line agent, while 32% escalate after failure of one first-line agent 4

Rituximab as Preferred Second-Line Agent

• Rituximab is chosen by 80% of experts for cases with unknown antibodies 4, 3
• Dosing: 375 mg/m² weekly for 4 weeks OR 1000 mg on days 1 and 15 2
• Improvement typically begins 1-2 weeks after first dose, though NMDAR encephalitis characteristically has slower response times 2

Cyclophosphamide Alternative

• Consider for cell-mediated autoimmunity or classical paraneoplastic syndromes 4, 3
• Only 10% of experts choose cyclophosphamide in scenarios with unknown antibodies 4

Bridging and Maintenance Therapy

After achieving clinical improvement, initiate bridging therapy to prevent relapse: 1, 2

• Gradual oral prednisone taper, OR
• Monthly IVIG, OR
• Monthly intravenous methylprednisolone 1
• Serial antibody monitoring in serum and CSF guides treatment duration 2

Refractory Cases

• For patients refractory to standard first and second-line therapies, consider experimental therapies including tocilizumab (IL-6 inhibitor) or bortezomib 4, 2

Special Considerations

Immune Checkpoint Inhibitor-Related Cases

• Permanently discontinue the checkpoint inhibitor 3
• These cases are particularly steroid-responsive 4

Paraneoplastic Encephalitis

• Only 48.5% of experts choose corticosteroids as first-line for classical paraneoplastic encephalitis 4
• Tumor removal is typically required and prognosis is often poor 5

Common Pitfalls to Avoid

• Do not delay treatment waiting for antibody results—commercial panels are often unavailable during early evaluation and many cases are seronegative 4, 6
• Thyroid antibody positivity alone does not confirm autoimmune encephalitis; 73% of patients referred with suspected Hashimoto encephalopathy have alternative diagnoses 6
• Ensure CSF inflammatory findings are present before diagnosing autoimmune encephalitis, as this distinguishes true responders from non-responders 6
• Do not misdiagnose functional neurological disorder—look for objective findings including abnormal brain MRI, abnormal EEG, CSF inflammation, seizures, stroke-like episodes, aphasia, or ataxia 6