Neurological Adverse Events in Immunotherapy

Immunotherapy with immune checkpoint inhibitors has revolutionised cancer treatment by unleashing T-cell responses against tumours, yet it can precipitate immune-related adverse events affecting both central and peripheral components of the nervous system. Neurological manifestations range from mild sensory disturbances and neuropathic pain to severe central inflammation, neuromuscular junction failure and paraneoplastic syndromes. Although these events occur in a minority of patients, typically between 1 and 5 per cent, they may emerge early in therapy and carry a risk of substantial morbidity and mortality if unrecognised. Underlying mechanisms include aberrant activation of autoreactive lymphocytes, generation of novel autoantibodies and unmasking of pre-existing subclinical autoimmunity. Clinical evaluation often requires the differentiation of immune-mediated injury from metastatic progression or treatment-related toxicity. Diagnosis relies on a combination of clinical assessment, neuroimaging, electrophysiology and emerging molecular biomarkers. Management balances the need for rapid immunosuppression—using corticosteroids, intravenous immunoglobulin or plasmapheresis—against preserving antitumour efficacy. Future efforts aim to stratify risk through pre-treatment immunological profiling and to refine non-invasive monitoring tools to detect early neuronal injury.

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Neurological Adverse Events in Immunotherapy publication trend

The graph below shows the total number of articles in neurological adverse events in immunotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint inhibitor (ICI): A therapeutic antibody targeting inhibitory receptors on T cells to boost antitumour immunity.

Immune-related adverse event (irAE): An unintended inflammatory toxicity in normal tissues caused by enhanced immune activation.

Biomarker: A measurable molecule or parameter that indicates a biological process or disease state.

Neurofilament light chain (NfL): A neuronal structural protein released into the blood upon axonal damage.

S100-calcium-binding protein B (S100B): A glial-derived protein that increases in circulation during central nervous system inflammation.

Myasthenia gravis: An autoimmune disorder of the neuromuscular junction characterised by fluctuating skeletal muscle weakness.

Encephalitis: Inflammation of the brain parenchyma presenting with altered consciousness, seizures or focal neurological deficits.

References

1. Concentrations of S100B and neurofilament light chain in blood as biomarkers for checkpoint inhibitor–induced CNS inflammation. EBioMedicine (2024).
2. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study. Journal for ImmunoTherapy of Cancer (2019).
3. Neurological Immune Related Adverse Events Associated with Nivolumab, Ipilimumab, and Pembrolizumab Therapy—Review of the Literature and Future Outlook. Journal of Clinical Medicine (2019).
4. Immune Checkpoint Inhibitor-Induced Myasthenia Gravis. Frontiers in Neurology (2020).