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)