What is the treatment approach for autoimmune encephalitis?

Treatment Approach for Autoimmune Encephalitis

The first-line treatment for autoimmune encephalitis is high-dose corticosteroids (intravenous methylprednisolone), which should be initiated immediately once infection is ruled out based on cerebrospinal fluid results. 1, 2

Diagnostic Workup Prior to Treatment

• Evaluate the likelihood of autoimmune encephalitis based on clinical presentation, including behavioral changes, seizures, and autonomic dysfunction 1
• Perform brain MRI and EEG to identify focal or multifocal brain abnormalities 1
• Conduct lumbar puncture to confirm inflammatory etiology and exclude infectious causes 1
• Test for neuronal autoantibodies in both cerebrospinal fluid and serum 1
• Consider brain FDG-PET when clinical suspicion is high but other studies are uninformative 1
• Perform cancer screening with contrast-enhanced CT of chest, abdomen, and pelvis in relevant cases 1

First-Line Treatment Algorithm

• Start high-dose corticosteroids (intravenous methylprednisolone 1-2 mg/kg/day or pulse dosing at 1g daily for 3-5 days) once infection is ruled out 1, 2
• Consider IVIG (0.4 g/kg/day for 5 days) as first-line therapy instead of steroids in patients with:
  • Contraindications to steroids (uncontrolled hypertension, diabetes, acute peptic ulcer) 1
  • Agitated or combative patients 3, 2
  • Patients with bleeding disorders 3, 2
• Consider PLEX (5-10 sessions performed every other day) as first-line therapy in patients with:
  • Severe hyponatremia 1, 3
  • High thromboembolic risk 1, 3
  • Associated brain or spinal demyelination 3, 2

Treatment Escalation

• If no clinical, radiological, or electrophysiological improvement is observed after initial treatment with corticosteroids, add IVIG or PLEX 1, 3
• For severe initial presentations (e.g., NMDAR-antibody encephalitis, new-onset refractory status epilepticus, severe dysautonomia), consider combination therapy with steroids plus IVIG or steroids plus PLEX from the beginning 1, 3
• If no improvement 2-4 weeks after completion of combined acute therapy, initiate second-line therapy 1

Second-Line Treatment

• Rituximab is the preferred second-line agent for antibody-mediated autoimmune encephalitis (e.g., NMDAR-antibody encephalitis) 1, 2
• Consider cyclophosphamide for cell-mediated autoimmunity (e.g., classical paraneoplastic syndrome) 1, 2
• For patients who fail to respond to conventional second-line therapies, consider experimental treatments such as:
  • IL-6 inhibitors (tocilizumab) 1, 4
  • Bortezomib (plasma cell-depleting agent) 1, 4
  • Intrathecal methotrexate for refractory cases 5

Supportive Care

• Manage seizures with appropriate antiepileptic medications 1
• Monitor and treat blood pressure and heart rate fluctuations in patients with dysautonomia 1
• Consider temporary pacemaker for severe dysrhythmia 1
• Implement fluid restriction for hyponatremia related to inappropriate antidiuretic hormone secretion 1
• Monitor intracranial pressure in cases with massive inflammation and brain edema 1

Common Pitfalls and Caveats

• Delaying immunotherapy while waiting for antibody test results can worsen outcomes; treatment should be initiated promptly once infection is ruled out 1, 6
• Failure to screen for underlying malignancy may miss paraneoplastic causes of autoimmune encephalitis 1
• Underestimating the need for escalation to second-line therapy can lead to incomplete recovery and residual neurologic deficits 7
• For immune checkpoint inhibitor-related autoimmune encephalitis, the checkpoint inhibitor should be permanently discontinued 2
• Despite clinical improvement with empiric therapy, recovery is often incomplete with substantial residual neurologic deficits 7

Current treatment algorithms are primarily based on observational studies, retrospective series, and expert opinion rather than randomized controlled trials, highlighting the need for higher quality evidence-based therapies 7, 8.