Schwenkenbecher Philipp, Chacko Lisa, Pul Refik, Sühs Kurt-Wolfram, Wegner Florian, Wurster Ulrich, Stangel Martin, Skripuletz Thomas
a Clinical Neuroimmunology and Neurochemistry, Department of Neurology , Hannover Medical School , Hannover , Germany.
b Department of Neurology , Essen University Hospital , Essen , Germany.
Int J Neurosci. 2018 Aug;128(8):721-728. doi: 10.1080/00207454.2017.1412967. Epub 2017 Dec 18.
The paraneoplastic cerebellar syndrome presents as severe neuroimmunological disease associated with malignancies. Antibodies against antigens expressed by tumor cells cross-react with proteins of cerebellar Purkinje cells leading to neuroinflammation and neuronal loss. These antineuronal antibodies are preferentially investigated by serological analyses while examination of the cerebrospinal fluid is only performed infrequently. We retrospectively investigated 12 patients with antineuronal antibodies against Purkinje cells with a special focus on cerebrospinal fluid. Our results confirm a subacute disease with a severe cerebellar syndrome in 10 female patients due to anti-Yo antibodies associated mostly with gynecological malignancies. While standard cerebrospinal fluid parameters infrequently revealed pathological results, all patients presented oligoclonal bands indicating intrathecal IgG synthesis. Analyses of anti-Yo antibodies in cerebrospinal fluid by calculating the antibody specific index revealed intrathecal synthesis of anti-Yo antibodies in these patients. In analogy to anti-Yo syndrome, an intrathecal production of anti-Tr antibodies in one patient who presented with a paraneoplastic cerebellar syndrome was detected. In an additional patient, anti-Purkinje cell antibodies of unknown origin in the cerebrospinal fluid but not in serum were determined suggesting an isolated immune reaction within the central nervous system (CNS) and underlining the importance of investigating the cerebrospinal fluid. In conclusion, patients with a cerebellar syndrome display a distinct immune reaction within the cerebrospinal fluid including intrathecal synthesis of disease-specific antibodies. We emphasize the importance of a thorough immunological work up including investigations of both serum and cerebrospinal fluid.
副肿瘤性小脑综合征表现为与恶性肿瘤相关的严重神经免疫性疾病。针对肿瘤细胞表达抗原的抗体与小脑浦肯野细胞的蛋白质发生交叉反应，导致神经炎症和神经元丧失。这些抗神经元抗体优先通过血清学分析进行检测，而脑脊液检查仅偶尔进行。我们回顾性研究了12例针对浦肯野细胞的抗神经元抗体患者，特别关注脑脊液情况。我们的结果证实，10例女性患者因抗Yo抗体出现亚急性疾病伴严重小脑综合征，这些抗体大多与妇科恶性肿瘤相关。虽然标准脑脊液参数很少显示出病理结果，但所有患者均出现寡克隆带，表明鞘内IgG合成。通过计算抗体特异性指数分析脑脊液中的抗Yo抗体，发现这些患者存在鞘内抗Yo抗体合成。与抗Yo综合征类似，在1例表现为副肿瘤性小脑综合征的患者中检测到鞘内抗Tr抗体产生。在另外1例患者中，脑脊液中而非血清中检测到来源不明的抗浦肯野细胞抗体，提示中枢神经系统内存在孤立的免疫反应，强调了检查脑脊液的重要性。总之，患有小脑综合征的患者在脑脊液中表现出独特的免疫反应，包括疾病特异性抗体的鞘内合成。我们强调全面免疫检查的重要性，包括对血清和脑脊液的检查。
