Brashear H R, Greenlee J E, Jaeckle K A, Rose J W
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908.
Neurology. 1989 Dec;39(12):1605-9. doi: 10.1212/wnl.39.12.1605.
Several groups of investigators have confirmed the occurrence of antibodies to Purkinje and other cerebellar neuronal populations in the serum and spinal fluid of patients with paraneoplastic cerebellar degeneration. Although this antibody response suggests that paraneoplastic cerebellar degeneration may have an autoimmune basis, it is not known what role anticerebellar antibodies play in the pathogenesis of this disorder or whether the presence of antibodies invariably results in cerebellar injury. We identified 3 patients with ovarian malignancies in whom high titers of circulating anticerebellar antibodies were present without clinical evidence of cerebellar disease. We followed these patients clinically and serologically until their deaths from their neoplasms. All 3 patients remained neurologically normal. In 2 of the patients, anticerebellar antibodies persisted at high titer. CSF obtained from 1 of these patients postmortem did not contain detectable levels of anticerebellar antibody, but histopathologic examination of her cerebellum revealed patchy loss of Purkinje cells. In the 3rd patient, antibody titers fell with removal of the primary tumor and chemotherapy but did not rise with tumor recurrence. Indirect immunofluorescence did not reveal anticerebellar antibodies in the serum or CSF of other patients with neoplasms, patients with other cerebellar disease, or normal controls. The present study demonstrates that patients with ovarian malignancies may occasionally develop antibodies that react with cerebellar neuronal antigens and can maintain this antibody response for protracted periods of time without clinically evident cerebellar injury. Tumor recurrence may not be accompanied by rise in titers of anticerebellar antibodies.
几组研究人员已经证实在副肿瘤性小脑变性患者的血清和脑脊液中存在针对浦肯野细胞和其他小脑神经元群体的抗体。尽管这种抗体反应提示副肿瘤性小脑变性可能有自身免疫基础，但尚不清楚抗小脑抗体在该疾病的发病机制中起什么作用，也不清楚抗体的存在是否必然导致小脑损伤。我们确定了3例卵巢恶性肿瘤患者，他们循环中存在高滴度的抗小脑抗体，但没有小脑疾病的临床证据。我们对这些患者进行了临床和血清学随访，直至他们死于肿瘤。所有3例患者神经功能均正常。其中2例患者抗小脑抗体持续保持高滴度。其中1例患者死后获得的脑脊液中未检测到可检测水平的抗小脑抗体，但对其小脑进行组织病理学检查发现浦肯野细胞有散在丢失。在第3例患者中，抗体滴度随着原发肿瘤的切除和化疗而下降，但未随肿瘤复发而升高。间接免疫荧光法未在其他肿瘤患者、其他小脑疾病患者或正常对照者的血清或脑脊液中检测到抗小脑抗体。本研究表明，卵巢恶性肿瘤患者可能偶尔会产生与小脑神经元抗原反应的抗体，并能在很长一段时间内维持这种抗体反应，而无明显的小脑损伤临床证据。肿瘤复发可能并不伴有抗小脑抗体滴度的升高。
