Limbic encephalitis is a
paraneoplastic syndrome that is often associated with
small cell lung cancer (SCLC),
breast cancer,
testicular tumors,
teratoma,
Hodgkin's lymphoma and
thymoma. The common clinical manifestations of
limbic encephalitis are subacute onset,
cognitive dysfunction,
seizures and psychiatric symptoms. Paraneoplastic
neurological disorders are considered to occur because of cytotoxic T cell responses and
antibodies against target neuronal
proteins that are usually expressed by an underlying
tumor. The main intracellular
antigens related to
limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and
amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal
encephalomyelitis such as
limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with
encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with
limbic encephalitis have
sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze
palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody
encephalitis is almost always associated with testicular
germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common
tumors are non-SCLC and
breast cancer.
Limbic encephalitis associated with
cell-surface antigens (e.g.,
voltage-gated potassium channels,
NMDA receptors) is mediated by
antibodies and often improves after a reduction in the antibody titer and after
tumor resection. Patients with
antibodies against intracellular
antigens, except for those with anti-Ma2
antibodies and
testicular tumors, are less responsive. Early diagnosis and treatment with
immunotherapy,
tumor resection or both are important for improving or stabilizing the condition of
limbic encephalitis.