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Paraneoplastic neurologic disorders and neurologic complications of immune checkpoint inhibitors

Smathorn Thakolwiboon1, Anastasia Zekeridou2

  • 1Department of Neurology, Mayo Clinic Health System, La Crosse, WI, United States; Center of Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, United States.

Handbook of Clinical Neurology
|January 12, 2026
PubMed

Insights

Paraneoplastic neurologic syndromes (PNS) arise from cancer-triggered immune responses. Immune checkpoint inhibitors (ICIs) can cause similar neurologic side effects, mimicking PNS.

Area of Science:

  • Neurology
  • Oncology
  • Immunology

Background:

  • Paraneoplastic neurologic syndromes (PNS) are rare neurological disorders caused by the immune system's response to cancer.
  • Immune checkpoint inhibitors (ICIs) are a novel cancer therapy that can trigger immune-related adverse events (irAEs).

Purpose of the Study:

  • To discuss the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of PNS.
  • To review neurologic irAEs associated with ICI therapy that may resemble PNS.

Main Methods:

  • Literature review and synthesis of existing research on PNS and ICI-related neurologic toxicities.
  • Discussion of clinical case examples and diagnostic criteria.

Main Results:

  • PNS and ICI-induced neurologic irAEs share overlapping clinical and immunopathologic features.
  • Early recognition and appropriate management are crucial for both conditions.

Conclusions:

  • Understanding the similarities and differences between PNS and ICI-related neurologic irAEs is vital for accurate diagnosis and effective treatment.
  • Further research is needed to elucidate the specific mechanisms and develop targeted therapies.
Keywords:
Cancer immunotherapyCerebellar ataxiaEncephalitisImmune-related adverse eventsMyositis

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