Treatment Approach for IgLON5-Related Disorders
Early initiation of intravenous immunoglobulins (IVIG) within the first year of disease onset is the treatment of choice for anti-IgLON5 disease, as it is the only immunotherapy associated with improved long-term disability outcomes and survival. 1
Immediate Treatment Strategy
Start IVIG within the first 12 months of symptom onset to maximize therapeutic benefit. Patients who received IVIG early had significantly lower disability scores (median mRS 2 vs 3) and lower mortality (0% vs 37.5%) compared to those receiving other immunotherapies or delayed treatment. 1
First-Line Therapy
- IVIG is the preferred initial immunotherapy based on the only modifiable independent factor associated with both lower long-term disability (OR 0.32) and improved survival (OR 2.70) when started early. 1
- Early immunotherapy (within first year) was associated with better outcomes regardless of agent, but only IVIG demonstrated statistically significant superiority over other early treatments. 1
Second-Line and Combination Approaches
- High-dose intravenous methylprednisolone can be used in combination with IVIG, particularly in patients with rapidly progressive cognitive decline or severe symptoms. 2
- Plasmapheresis may be added to IVIG and corticosteroids for patients with severe or refractory symptoms, with documented improvement in both neuropsychological deficits and antibody titers. 2
- Rituximab was used in 52% of early-treated patients but did not show the same favorable outcomes as IVIG monotherapy. 1
Critical Timing Considerations
The window for optimal treatment is narrow—immunotherapy must begin within the first year. Patients who received no treatment or only IV corticosteroids alone had higher mortality than those treated with more potent immunotherapy. 3 The 23.4% of patients who received early treatment had substantially better outcomes than the 53.3% who received delayed treatment. 1
Treatment Pitfalls to Avoid
- Do not delay treatment while pursuing extensive diagnostic workup—if clinical features are consistent with anti-IgLON5 disease and antibodies are positive in serum or CSF, begin IVIG immediately. 1
- Avoid using corticosteroids as monotherapy, as this approach is associated with higher mortality compared to more aggressive immunotherapy. 3
- Do not assume all immunotherapies are equivalent—rituximab and other agents used early did not demonstrate the same survival benefit as IVIG. 1
Expected Response and Prognosis
The response to immunotherapy in anti-IgLON5 disease is generally suboptimal compared to other autoimmune encephalitides, with most patients showing only partial improvement. 3, 4 However, aggressive early immunotherapy with IVIG significantly increases survival—overall mortality in the disease is 41.1%, with at least two-thirds of deaths directly related to anti-IgLON5 disease. 1
Clinical Monitoring
Monitor for the characteristic symptom complex: severe insomnia with NREM parasomnia, sleep-disordered breathing (stridor and obstructive sleep apnea), bulbar involvement, gait instability, movement disorders, oculomotor abnormalities, dysautonomia, and cognitive decline. 3, 4 Antibody titers in both serum and CSF should be followed, as they may correlate with treatment response. 2
Long-Term Management
Patients typically follow a chronic progressive course despite treatment. 4 The disease involves a complex interplay between autoimmunity and neurodegeneration, with secondary tauopathy developing in patients with prolonged clinical courses. 4 Maintenance immunotherapy strategies beyond the acute phase remain poorly defined and require individualized assessment based on clinical response and disease trajectory. 3, 4