What is the treatment for IgLON5 encephalitis?

Treatment for IgLON5 Encephalitis

Immunotherapy is the cornerstone of treatment for IgLON5 encephalitis, with early initiation of combined immunosuppressive agents showing the best outcomes for reducing morbidity and mortality. 1

First-Line Immunotherapy Options

• High-dose intravenous methylprednisolone (1g daily for 3-5 days) is recommended as initial treatment, based on successful outcomes in autoimmune encephalitis cases 2, 3
• Intravenous immunoglobulin (IVIG) should be administered in conjunction with steroids, as combination therapy appears more effective than monotherapy 2, 3
• Plasma exchange is an alternative or additional first-line treatment option when response to steroids and IVIG is suboptimal 2
• Early initiation of immunotherapy (within the first 6 weeks of symptom onset) is a significant predictor of treatment response 1

Treatment Algorithm

1. Initial Diagnosis Phase:

   • Confirm diagnosis with anti-IgLON5 antibody testing in both serum and CSF 4
   • Assess for inflammatory CSF changes, which are present in approximately 37% of cases 1
   • Evaluate for blood-CSF barrier disturbance, found in about 46% of patients 1

2. Acute Treatment Phase:

   • Begin with high-dose methylprednisolone (1g IV daily for 5 consecutive days) 5
   • Add IVIG (standard dose 0.4g/kg/day) concurrently for synergistic effect 2, 3
   • Consider plasma exchange if response is inadequate 2

3. Maintenance Phase:

   • Long-term immunosuppression is necessary in most cases 1
   • Monthly high-dose steroid pulses may be beneficial for maintenance therapy 5
   • Consider second-line agents for refractory cases or maintenance (see below)

Second-Line and Long-Term Treatment Options

• For patients with inadequate response to first-line therapy, consider:
  • Rituximab or cyclophosphamide have shown success in refractory cases of autoimmune encephalitis 2
  • Azathioprine may be helpful for long-term immunosuppression to prevent relapses 2
  • Long-term immunotherapy initiated within the first year after symptom onset is associated with better outcomes 1

Monitoring and Outcome Assessment

• Regular assessment of clinical symptoms including sleep disorders, bulbar symptoms, and cognitive function 5
• Monitor serum anti-IgLON5 IgG titers, which tend to increase with disease duration 1
• Serum neurofilament light chain levels may serve as a biomarker for treatment response - lower pre-treatment levels predict better outcomes 1
• Approximately 75% of patients on long-term immunotherapy experience no further disease progression 1

Prognostic Factors and Pitfalls

• Without treatment, IgLON5 disease has a high mortality rate 4
• Treatment with IV corticosteroids alone shows poorer outcomes compared to more aggressive combined immunotherapy 4
• Disease duration before treatment initiation significantly impacts prognosis - early diagnosis and treatment are crucial 1
• Patients with subacute onset (28% of cases) may respond better to immunotherapy than those with insidious onset 1
• The presence of HLA-DRB1*10:01 is associated with higher antibody titers and may influence disease course 1

Common Pitfalls to Avoid

• Delaying immunotherapy while awaiting complete diagnostic workup can worsen outcomes 1
• Failing to recognize the heterogeneous clinical presentation of IgLON5 disease, which can include sleep disorders, bulbar symptoms, movement disorders, and cognitive impairment 4, 5
• Discontinuing immunotherapy prematurely, as long-term treatment is often necessary 1
• Underestimating the importance of combination therapy rather than monotherapy 2, 4