teratomas are associated with anti NMDA receptor encephalitis

Autoimmune paraneoplastic syndromes often lead to severe encephalopathy, seizures, and eventually death. Until recently, the most common precipitating illness for these diseases was small cell lung cancer (SCLC). In the past 10 to 15 years, a new syndrome has been described, the anti-NMDA (N-methyl-D-aspartate) receptor encephalitis syndrome, which is associated with benign ovarian and testicular teratomas. This newly discovered paraneoplastic syndrome is associated with antibodies against the NMDA receptor, an important glutaminergic calcium channel that is important for memory development and higher-order cognitive processes. This syndrome occurs more often in younger patients and is associated with benign teratomas, particularly in the ovaries and testis (choice D is correct). Opsiclonus-myoclonus is most commonly associated with SCLC in older patients (or primitive neuroendocrine tumors in children) (choice A is incorrect). Retinal blindness is typically associated with breast cancer (choice B is incorrect). The Lambert-Eaton myasthenia syndrome is often associated with SCLC but can be associated with breast cancer and lymphosarcoma (choice C is incorrect).

The anti-NMDA receptor encephalitis syndrome associated with antibodies against the NMDA-receptor is a unique paraneoplastic syndrome for a number of reasons. First, it has an atypical presentation dissimilar from most other paraneoplastic syndromes. Patients with the anti-NMDA receptor encephalitis syndrome usually initially manifest with paranoia and psychosis followed by progressive encephalopathy and seizures until one of three things happens: the patient is treated, the syndrome resolves spontaneously, or the patient succumbs. Second, this syndrome attacks young adults most commonly (which is an uncommon time to develop a paraneoplastic syndrome). Third, although all the paraneoplastic syndromes can be associated with nonmalignant as well as malignant diseases, the majority of patients with anti-NMDA receptor encephalitis are found to have nonmalignant diseases, with benign teratomas being the most common.

The hallmark of paraneoplastic illnesses is the development of monoclonal (or occasionally polyclonal) antibody responses that cross-react with neuronal or motor endplate proteins, causing their destruction. The symptoms caused by the antibody response depend on the location of the neuron or neuromuscular junction that expresses the specific antigen protein. Likewise, different tumors/disorders have a propensity to express a particular protein, leading to a specific antibody response allowing a rough pairing between cancer and response.

SCLC is the most common cancer associated with paraneoplastic diseases for a number of reasons. First, a number of paraneoplastic syndromes are associated with SCLC, including the anti-Hu, anti-Ri, anti-Ma, and anti-Ta paraneoplastic syndromes. Second, SCLC is a common cancer. And third, SCLC often expresses neuroendocrine features, which allows presentation of specific antigens not usually found outside the nervous system.

Treatment for all paraneoplastic syndromes focuses on stopping production of or removing the antibody with plasmapheresis or IV immunoglobulin followed by suppression of the immune response with immunomodulatory medications.## Links to this note