What is the treatment for IgLON5 (Immunoglobulin-like cell adhesion molecule 5) encephalitis?

Treatment for IgLON5 Encephalitis

Early initiation of intravenous immunoglobulins (IVIg) within the first year of disease onset is strongly recommended as the first-line treatment for IgLON5 encephalitis, as it is associated with improved long-term outcomes and survival. 1

Clinical Presentation and Diagnosis

IgLON5 encephalitis is a recently identified autoimmune encephalopathy characterized by:

• Sleep disorders (severe insomnia, NREM parasomnia with finalistic movements, sleep-disordered breathing)
• Bulbar symptoms (dysphagia, dysarthria)
• Movement disorders (gait instability, chorea)
• Cognitive impairment
• Oculomotor abnormalities
• Dysautonomia
• Potential for central hypoventilation 2

The disease typically presents in two phases:

1. Initial phase: seizures, confusion, amnesia, and psychosis
2. Later phase: involuntary movements (choreathetosis, orofacial dyskinesia), fluctuating consciousness, dysautonomia, and central hypoventilation 3

Treatment Algorithm

First-Line Treatment

1. Intravenous immunoglobulins (IVIg) at 0.4 g/kg/day

   • Should be initiated as early as possible, ideally within the first year of symptom onset
   • Associated with significantly better outcomes (median mRS score 2 vs 3) and improved survival 1

2. High-dose corticosteroids

   • Methylprednisolone 1g IV daily for 3-5 consecutive days 4
   • Can be used in conjunction with IVIg for enhanced efficacy 3

Second-Line Treatment (for inadequate response to first-line therapy)

1. Plasma exchange should be considered in patients who respond poorly to corticosteroids and IVIg 3

Third-Line Treatment (for refractory cases)

1. Rituximab or cyclophosphamide for patients who don't respond adequately to first and second-line treatments 3

Long-Term Management

1. Maintenance immunosuppression with agents such as azathioprine may be necessary, particularly in patients who experience relapses 3
2. Regular neurological evaluation to monitor treatment response
3. Follow-up CSF analysis to assess immunological response 5

Prognostic Factors

Factors associated with better treatment response:

• Early initiation of immunotherapy (within first 6 weeks for acute exacerbations) 5
• Treatment within the first year of disease onset 1
• Low pre-treatment neurofilament light chain levels 5

Important Considerations

• Without treatment, IgLON5 encephalitis has a high mortality rate and significant disability 2
• Approximately 41% of patients respond to first-line immunotherapy during acute-to-subacute exacerbations 5
• With appropriate long-term immunotherapy, about 75% of patients experience no further disease progression 5
• Patients treated with IV corticosteroids alone have higher mortality compared to those receiving more aggressive immunotherapy 2

Monitoring and Follow-up

• Regular neurological examinations to assess treatment response
• CSF analysis to monitor inflammatory markers and antibody levels
• Screening for associated tumors, particularly ovarian teratomas in female patients 3
• Long-term immunosuppression may be required to prevent relapses, which occur in approximately 30% of patients 3

The evidence strongly supports early and aggressive immunotherapy, with IVIg showing particular benefit when initiated within the first year of disease onset. This approach offers the best chance for improved functional outcomes and survival in this potentially devastating disorder.