Anti-CASPR2 encephalitis

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Anti-CASPR2 encephalitis is an autoimmune encephalitis with multisystemic involvement.

It can present with psychiatric features such as anxiety, agitation, mood symptoms, sleep disturbance, confusion, behavioural change, hallucinations, and psychosis, particularly in the context of encephalopathy.

Other characteristic features include encephalitis with cognitive impairment, seizures, and altered mental status; peripheral nerve hyperexcitability syndromes including neuromyotonia (continuous muscle fibre activity), muscle cramps, fasciculations, and myokymia; Morvan syndrome features including severe insomnia, autonomic dysfunction, and painful muscle cramps; and cerebellar ataxia in some cases.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Cardiovascular: autonomic dysfunction, including fluctuations in heart rate and blood pressure, may occur, particularly in Morvan syndrome.

  • Respiratory: thymoma-related respiratory symptoms may occur due to mediastinal mass effects.

  • Gastrointestinal: autonomic gastrointestinal dysfunction may occur, including constipation and altered gastrointestinal motility, particularly in Morvan syndrome.

  • Musculoskeletal: muscle cramps and stiffness may occur due to peripheral nerve hyperexcitability.

  • Endocrine: association with underlying malignancy, particularly thymoma, in some cases.

  • Hematologic: thymoma-associated immune dysregulation may occur in association with the underlying tumour.

Early diagnosis is important to enable prompt immunotherapy, reduce the risk of persistent cognitive impairment, seizures, functional decline, and complications related to autonomic dysfunction, guide investigation for associated malignancy when appropriate, and improve prognosis and quality of life.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.