Paraneoplastic Limbic Encephalitis

Paraneoplastic syndrome is a rare immune-mediated complication that arises as a remote effect of cancer, often occurring covertly. This syndrome can manifest in various clinical presentations, including encephalitis, Lambert-Eaton myasthenic syndrome, typical abdominal symptoms associated with neuroblastoma such as severe constipation and chronic flatulence, myelopathies, movement disorders, new-onset hyperglycemia, intrahepatic cholestasis, and various endocrine symptoms involving corticotropin-releasing hormone, adrenocorticotropic hormone, antidiuretic hormone, among others.

Paraneoplastic limbic encephalitis (LE) is a specific paraneoplastic syndrome characterized by inflammation and injury to the limbic structures, resulting in specific neuropsychiatric syndromes. Common clinical presentations include memory impairment, psychosis, mood and behavioral disturbances, cognitive decline, abnormal movements, altered levels of consciousness, dysautonomia, and seizures. Amygdala involvement may cause emotional disturbances and aggressive behavior, while hypothalamic involvement can disrupt appetite and libido.

Concerning the pathogenesis of paraneoplastic LE, autoantibodies fall into 2 primary categories. The first group targets cell-surface or synaptic antigens, provoking pathogenic responses that trigger antibody and complement-mediated immune damage. The second group targets intracellular antigens, specifically the classical onconeural antigens; these antibodies do not directly induce pathogenesis. Instead, the immunological injury is predominantly cell-mediated cytotoxicity. This second group is also more frequently associated with paraneoplastic syndromes, whereas antibodies directed against cell surface and synaptic antigens are often not paraneoplastic.

The best approach for treating paraneoplastic LE involves addressing the underlying cancer if present. Repeated surveillance to detect any potential underlying cancer is indicated when no underlying cancer is identified, and immunotherapy can be a beneficial strategy for managing the syndrome.