Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma.
We report four young women who developed acute psychiatric symptoms, seizures, memory deficits, decreased level of consciousness, and central hypoventilation associated with ovarian teratoma (OT) and cerebrospinal fluid (CSF) inflammatory abnormalities. Three patients recovered with treatment of the tumor or immunosuppression and one died of the disorder. Five other OT patients with a similar syndrome and response to treatment have been reported. Our patients' serum or CSF showed immunolabeling of antigens that were expressed at the cytoplasmic membrane of hippocampal neurons and processes and readily accessed by antibodies in live neurons. Immunoprobing of a hippocampal-expression library resulted in the isolation of EFA6A, a protein that interacts with a member of the two-pore-domain potassium channel family and is involved in the regulation of the dendritic development of hippocampal neurons. EFA6A-purified antibodies reproduced the hippocampal immunolabeling of all patients' antibodies and colocalized with them at the plasma membrane. These findings indicate that in a young woman with acute psychiatric symptoms, seizures, and central hypoventilation, a paraneoplastic immune-mediated syndrome should be considered. Recognition of this disorder is important because despite the severity of the symptoms, patients usually recover. The location and function of the isolated antigen suggest that the disorder is directly mediated by antibodies.
Vitaliani
Roberta
R
Division of Neuro-oncology, Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mason
Warren
W
Ances
Beau
B
Zwerdling
Theodore
T
Jiang
Zhilong
Z
Dalmau
Josep
J
D000293:Adolescent; D000328:Adult; D000818:Animals; D000912:Antibodies, Neoplasm / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002478:Cells, Cultured; D004660:Encephalitis / Q000209:etiology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007040:Hypoventilation / Q000209:etiology*; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D001523:Mental Disorders / Q000209:etiology*; D009474:Neurons / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000150:complications*; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D013724:Teratoma / Q000150:complications*; D013997:Time Factors
D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D019788:Fluorodeoxyglucose F18