How to diagnose and manage neurological toxicities of immune checkpoint inhibitors: an update

J Neurol. 2022 Mar;269(3):1701-1714. doi: 10.1007/s00415-021-10870-6. Epub 2021 Oct 27.


As the use of cancer immunotherapy with immune checkpoint inhibitors (ICIs) is expanding rapidly for the treatment of many tumor types, it is crucial that both neurologists and oncologists become familiar with the diagnosis and treatment of neurological immune-related adverse events (n-irAEs). These are rare complications, developing in their severe forms in only 1-3% of the patients, but are highly relevant due to their mortality and morbidity burden. The diagnosis of n-irAEs is-however-challenging, as many alternative diagnoses need to be considered in the complex scenario of a patient with advanced cancer developing neurological problems. A tailored diagnostic approach is advisable according to the presentation, clinical history, and known specificities of n-irAEs. Several patterns characterized by distinct clinical, immunological, and prognostic characteristics are beginning to emerge. For example, myasthenia gravis is more likely to develop after anti-programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) treatment, while meningitis appears more frequently after anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) therapy. Also, peripheral neuropathy and Guillain-Barré syndrome seem to be more common in patients with an underlying melanoma. Central nervous system disorders (CNS) are less frequent and are more often associated with lung cancer, and some of them (especially those with limbic encephalitis and positive onconeural antibodies) have a poor prognosis. Herein, we provide an update of the recent advances in the diagnosis and treatment of neurological toxicities related to ICI use, focusing on the exclusion of alternative diagnoses, diagnostic specificities, and treatment of n-irAEs.

Keywords: Encephalitis; Immune checkpoint inhibitors; Myositis; Neurologic adverse events; Neurological complications.

MeSH terms

  • Humans
  • Immune Checkpoint Inhibitors
  • Immunotherapy / adverse effects
  • Lung Neoplasms* / drug therapy
  • Melanoma*
  • Neoplasms* / drug therapy
  • Prognosis


  • Immune Checkpoint Inhibitors