Psychiatric Manifestations of Paraneoplastic Disorders

Paraneoplastic disorders can lead to severe psychiatric and behavioural symptoms. Paraneoplastic limbic encephalitis (PLE) is a rare neurological syndrome associated with cancer, and selectively affects limbic system structures, including the hippocampus, hypothalamus, and amygdala.^[1] The encephalitis is caused by an altered immunologic response to a malignancy that has antigens that resemble limbic antigens. The inflammatory response, however, occurs away from the original neoplasm site.^[2]

The autoantibody response can be psychiatric in nature, and includes:

• NMDAR-antibody encephalitis, associated with ovarian teratomas in younger women
• Ophelia syndrome, associated with surface-directed mGluR5-antibodies, seen in patients with Hodgkin’s lymphoma
• Anti-neuronal nuclear antibody-1 (ANNA-1), also known as anti-Hu paraneoplastic encephalomyelitis, associated with small cell lung cancer in 75% of cases (other tumours include lung, prostate, breast, bladder, GI tract, ovary, neuroendocrine, unknown origin), most commonly in men.
• AMPA receptor antibodies, associated with lung, breast, thymus, ovarian tumours.

• Individuals with a personal or family cancer history, smoking history, should be worked up for paraneoplastic involvement.
  • The most common tumours associated with paraneoplastic limbic encephalopathy are small cell lung cancer (SCLC) (about 75% of cases), germ-cell tumours (ovarian or testicular), thymoma, Hodgkin's lymphoma, and breast cancer.
• The most common symptoms are a subacute cognitive (primarily amnestic) syndrome.
• Depression, anxiety, personality changes, and emotional lability can often precede the cognitive impairment.

• CSF evidence of inflammation
• Elevated tumor markers (e.g. - CEA, CA-125, PSA)

• Ahmed, R. M., Halmagyi, G. M., & Rodriguez, M. L. (2013). Rapidly progressive dementia and ataxia in an elderly man. Practical neurology, 13(3), 165-173.
• Geschwind, M. D., Haman, A., & Miller, B. L. (2007). Rapidly progressive dementia. Neurologic clinics, 25(3), 783-807.
• Kayser, M. S., Kohler, C. G., & Dalmau, J. (2010). Psychiatric manifestations of paraneoplastic disorders. American Journal of Psychiatry, 167(9), 1039-1050.
• Reville, P. K., & Steingraeber, C. (2016). ANNA-1 Paraneoplastic Encephalomyelitis Presenting as Rapidly Progressing Dementia in a Man With Undiagnosed Small Cell Lung Cancer. American Journal of Psychiatry Residents' Journal, 11(11), 13-15.