What is the initial treatment for IGLON5 (Immunoglobulin-like domain-containing protein 5) antibody-associated autoimmune encephalopathy?

Initial Treatment for IGLON5 Antibody-Associated Autoimmune Encephalopathy

Start with high-dose intravenous methylprednisolone (IVMP) as first-line therapy, using either standard dosing (1-2 mg/kg/day) or pulse therapy (1g daily for 3-5 days) for severe presentations, following the same treatment paradigm established for other antibody-mediated autoimmune encephalitides. 1, 2, 3

First-Line Immunotherapy Approach

• Initiate acute immunotherapy immediately once cerebrospinal fluid results exclude infection and primary CNS lymphoma or neurosarcoidosis are not considerations 1, 3

• High-dose corticosteroids (IVMP) are the preferred initial agent, as they represent the most commonly used and effective first-line therapy for antibody-mediated autoimmune encephalitis 1, 3

• Alternative first-line options include IVIG or plasma exchange (PLEX) if corticosteroids are contraindicated or in specific clinical scenarios 2, 3:

  • IVIG (0.4 g/kg/day for 5 days) is preferred for agitated/combative patients, those with bleeding disorders, or difficulty with central line placement 2
  • PLEX (5-10 sessions every other day) is preferred for severe hyponatremia, high thromboembolic risk, or associated demyelination 2

Evidence-Based Rationale for Anti-IgLON5 Disease

• Aggressive immunotherapy appears to increase survival in anti-IgLON5 disease, with cases receiving no treatment or corticosteroids alone showing higher mortality than those treated with more potent immunotherapy 4

• Most patients respond partially to immunotherapy, though the response may be less robust than in other autoimmune encephalitides due to the complex interplay between inflammation and tau-mediated neurodegeneration 4

• Glucocorticoid monotherapy can be highly effective in some patients, particularly those with a phenotype where autoimmunity plays a greater pathogenic role than tauopathy 5

Escalation to Second-Line Therapy

• Add rituximab or cyclophosphamide if no meaningful clinical or radiological response occurs after 2-4 weeks of optimized first-line therapy 3

• Rituximab is the preferred second-line agent for antibody-mediated autoimmune encephalitis, with standard dosing of 375 mg/m² weekly for 4 weeks or 1000 mg on days 1 and 15 1

• Cyclophosphamide should be considered for refractory cases, as case reports demonstrate clinical improvement in anti-IgLON5 disease following cyclophosphamide treatment when first-line therapies fail 6

• Plasmapheresis can be added to the treatment regimen for severe or refractory cases, with evidence showing improvement in both clinical symptoms and antibody titers 7

Critical Clinical Pitfalls

• Do not delay treatment waiting for antibody confirmation, as anti-IgLON5 disease has an insidious onset with slow progression that can mimic other neurological disorders 4

• Recognize that mild cases may exist and could potentially improve without aggressive immunotherapy, though this represents a minority of cases 8

• Be aware of the strong HLA association (HLA-DRB110:01 and HLA-DQB105:01), which may help support the diagnosis 4

• Test for antibodies in both serum and CSF, as CSF positivity appears to correlate with predominant clinical features when multiple antibodies coexist 6

Bridging and Maintenance Therapy

• After achieving clinical improvement, initiate bridging therapy with gradual oral prednisone taper, monthly IVIG, or monthly intravenous methylprednisolone to prevent relapse 2, 3

• Monitor serial antibody levels in serum and CSF to guide treatment duration and assess response 1