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Updated: Dec 20, 2025
Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007
Encephalomyeloneuritis and arthritis after treatment with immune checkpoint inhibitors
Martha Nowosielski1, Franziska Di Pauli2, Sarah Iglseder1
1From the Department of Neurology (M.N., F.D.P., S.I., G.S.); Department of Dermatology and Venerology (N.H., V.A.N.); Department of Radiology (M.W.); and Department of Internal Medicine (J.G.), Medical University Innsbruck, Austria.
Objective:
Immunotherapy revolutionized melanoma treatment; however, immune-related adverse events, especially neurotoxicity, may be severe and require early and correct diagnosis as well as early treatment commencement.
Methods:
We report an unusual severe multiorgan manifestation of neurotoxicity after treatment with the anti-PDL1 immune checkpoint inhibitor, nivolumab, and the anticytotoxic T-lymphocyte-associated antigen 4 immune checkpoint inhibitor, ipilimumab, in a 47-year-old male patient with metastatic melanoma.
Results:
The patient developed immune-mediated synovitis and cranial neuritis, followed by longitudinal transverse myelitis, encephalitis, and optic neuritis. Early treatment with high-dose steroids and maintenance therapy with rituximab resulted in a favorable neurologic outcome.
Conclusions:
The frequency of spinal cord involvement and neuronal toxicity after cancer immunotherapy is very low and requires an extensive diagnostic workup to differentiate between disease progression and side effects. Immune checkpoint inhibitors should be discontinued and treatment with corticosteroids should be initiated early as the drug of first choice. Therapy may be escalated by other immune-modulating treatments, such as rituximab.
Insights
Severe neurotoxicity from combined immunotherapy (nivolumab and ipilimumab) in melanoma patients is rare but serious. Early diagnosis and treatment with steroids and rituximab led to a favorable neurologic outcome.
Area of Science:
- Neuro-oncology
- Immunology
- Dermatology
Background:
- Immunotherapy, including immune checkpoint inhibitors (ICIs), has transformed melanoma treatment.
- Immune-related adverse events (irAEs), particularly neurotoxicity, can be severe and necessitate prompt management.
Observation:
- A 47-year-old male with metastatic melanoma developed severe multiorgan neurotoxicity after treatment with nivolumab (anti-PDL1) and ipilimumab (anti-CTLA-4).
- Manifestations included immune-mediated synovitis, cranial neuritis, longitudinal transverse myelitis, encephalitis, and optic neuritis.
Findings:
- High-dose corticosteroids initiated early, followed by rituximab maintenance therapy, resulted in a favorable neurologic outcome.
- The patient's neurotoxicity was characterized by a rare but severe multiorgan involvement.
Implications:
- Early diagnosis and intervention are critical for managing ICI-induced neurotoxicity.
- Discontinuation of ICIs and prompt corticosteroid treatment are recommended first-line therapies.
- Rituximab may be considered as an effective escalation therapy for severe cases.
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