Anti-Hu (ANNA-1) paraneoplastic encephalomyelitis

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-Hu (ANNA-1) paraneoplastic encephalomyelitis is an autoimmune condition with multisystemic involvement.

It can present with psychiatric features such as confusion, behavioural change, mood symptoms, anxiety, agitation, sleep disturbance, and psychosis, particularly in the context of paraneoplastic encephalomyelitis affecting the central nervous system.

Other characteristic features include multifocal neurological involvement due to paraneoplastic encephalomyelitis, which may include limbic encephalitis with memory impairment and seizures, sensory neuronopathy, cerebellar degeneration with ataxia, brainstem encephalitis, myelitis, autonomic dysfunction, and peripheral neuropathy. There is a strong association with underlying malignancy, particularly small-cell lung cancer.

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

  • Respiratory: association with small-cell lung cancer, which may present with respiratory symptoms or other tumour-related features.

  • Renal/electrolytes: hyponatremia may occur due to tumour-related SIADH, particularly in the context of associated small-cell lung cancer.

Early diagnosis is important to enable prompt identification and treatment of the underlying malignancy, initiate immunotherapy and supportive management when appropriate, and reduce the risk of irreversible neurological injury and progressive functional decline. Unlike some antibody-mediated encephalitis syndromes, established anti-Hu neurological syndromes are often less responsive to treatment, making early recognition particularly important for improving outcomes, 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.