What is the treatment for a patient with a positive IgLON5 (Immunoglobulin LON domain containing 5) antibody serum test result?

Treatment of IgLON5 Antibody-Associated Autoimmune Encephalitis

First-line treatment for IgLON5 antibody-associated autoimmune encephalitis should include high-dose intravenous methylprednisolone and intravenous immunoglobulin. 1, 2

Initial Treatment Approach

Corticosteroid Therapy

• For mild to moderate disease: Methylprednisolone 1-2 mg/kg/day IV 1
• For severe or progressive disease: Pulse-dose methylprednisolone 1g IV daily for 3-5 days 1, 3
• Taper steroids following acute management over at least 4-6 weeks 3

Immunoglobulin Therapy

• IVIG 2 g/kg total dose divided over 5 days (0.4 g/kg/day) should be administered concurrently with corticosteroids in moderate to severe cases 1, 3
• This combination therapy has shown rapid improvement in symptoms in case reports 2

Second-Line Therapies

For Refractory Cases

• Consider plasmapheresis if limited or no improvement with first-line therapies 3, 1
• Rituximab should be considered in consultation with neurology for cases with confirmed IgLON5 antibodies that don't respond to first-line treatment 3
• Cyclophosphamide may be considered in severe refractory cases 3

Clinical Monitoring and Follow-up

Neurological Assessment

• Obtain neurological consultation for all patients with suspected or confirmed IgLON5 disease 1, 3
• Regular clinical assessment for treatment response is essential, as IgLON5 disease often has a chronic progressive course 4
• Monitor for improvement in characteristic symptoms including:
  • Gait instability and movement disorders 2, 5
  • Bulbar dysfunction (dysphagia, dysarthria) 2, 6
  • Sleep disorders (parasomnias, sleep apnea) 4, 5
  • Cognitive impairment 5

Diagnostic Workup

• MRI brain (may show hypothalamic-bulbar hyperintensities in some cases, though often unremarkable) 6
• EEG to evaluate for subclinical seizures 3
• Lumbar puncture with CSF analysis (cell count, protein, glucose, oligoclonal bands) 3, 6
• Serum studies including autoimmune encephalitis panels 3

Treatment Challenges and Considerations

Response Patterns

• Unlike other autoimmune encephalitides, response to immunotherapy in IgLON5 disease is often suboptimal 4
• Early treatment initiation may improve outcomes, as the disease appears to cause irreversible antibody-mediated internalization of surface IgLON5 7
• Sustained clinical response to immunotherapy occurs in approximately 36% of patients 6

Important Caveats

• Rule out infectious causes before initiating immunosuppressive therapy 3
• Consider empiric antiviral therapy (IV acyclovir) until CSF results are available, especially when viral encephalitis cannot be excluded 3, 1
• IgLON5 disease has features of both autoimmune and neurodegenerative conditions, with neuropathology showing tau deposits in the hypothalamus and brainstem tegmentum in long-standing cases 4, 7
• The predominant antibody subclass is IgG4, but all patients also have IgG1 antibodies, with the latter potentially mediating pathogenic effects 7

Long-term Management

• Regular follow-up with neurology is essential due to the chronic nature of the disease 4
• Be vigilant for relapse, particularly when tapering corticosteroids 1
• Consider maintenance immunotherapy in patients who respond to initial treatment, though optimal regimens are not well established 4