Paraneoplastic temporal lobe epilepsy and anti-Yo autoantibody

Onconeural antigens have normaly limited expression in the central nervous system which is an immune sanctuary. Immune privilege of onconeural antigens fails when these antigens are expressed ectopically on tumors. The onconeural antigens become then immunogenic and the antibodies can give rise to autoimmune neuronal degeneration in a subset of patients [1]. One of these antibodies is called anti-Yo. Anti-Yo antibody are usually associated with paraneoplastic cerebellar degeneration. Clinical characteristics are ataxia, dysarthria, vertigo and nystagmus. Seropositive patients for the anti-Yo antibody are almost always female patients suffering from breast or gynecologic tumors [2]. We report a patient who presented with an endometrial adenocarcinoma metastatic evolution, anti-Yo antibodies and paraneoplastic temporal lobe epilepsy. In 1992, a 62-year-old woman presented with a stage Ic grade 1 endometrial carcinoma. The CA125 level was elevated to 169 U/ml (normal level is < 35 U/ml). She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic lymph node dissection and para-aortic lymph node sampling. Final pathology showed an adenocarcinom a with 75% myometrial invasion, negative peritoneal washing and negative pelvic and para-aortic lymph nodes. She received a 50 gray external pelvic irradiation postoperatively. At the end of the treatment, the CA125 level was under 35 U/ml. In May 1995, the CA125 level was 166 U/ml. The abdominal computed tomography (CT) demonstrated retroperitoneal lymphadenopathies. Hormonal therapy was introduced with medroxyprogesterone acetate. In November 1995, the CA125 level was under 35 U/ml and the size of retroperitone al lymphadenopathies decreased. In February 1996, the patient demonstrated first severe anterograde amnesia, olfactory hallucination, confusion speech and orofacial automatisms. These symptoms extended on two weeks then a generalized epilepsy appeared. The generalized epileptic seizure was treated by valium injection and an antiepileptic treatment with phenytoine was introduced. The brain CT with contrast and magnetic resonance imaging scan were considered normal for her age. The cerebrospinal fluid examination revealed a mild lymphocytic pleocytosis and elevation of protein. The abdominal CT showed a large increase of retroperitoneal tumors. The CA125 level was 206 U/ml. Anti-Yo antibodies were detected by immunohistochemistry and western blotting. The hormonotherapy was stopped and replaced by chemotherapy (CEP regimen: cyclophosphamide 500 mg/m2/d day 1, epirubicin 50 mg/m2/d day 1, cisplatine 50 mg/m2/d day 1, dl-d21) [3]. The antiepileptic treatment with phenytoine was stopped after one chemotherapy cycle. After four CEP cycles, there was a clinical complete response with no more neurological disorder and a radiological complete response on retroperitone al lymphadenopat hies. The CA125 level was under 35 U/ml. Anti-Yo antibodies were no more detected. Eight chemotherapy cycles have been completed before surgical excision of the residual tumor and peroperative radiotherapy. There is now a 10-month disease-freesurvival.