Progressive encephalomyelitis with rigidity and myoclonus A new variant with DPPX antibodies
Progressive encephalomyelitis with rigidity and myoclonus A new variant with DPPX antibodies
复制标题
DOI：
10.1212/wnl.0000000000000372
复制
发表时间：
2014-04-29
期刊：
影响因子：
9.9
通讯作者：
Meinck, Hans-Michael
中科院分区：
文献类型：
--
作者：
Balint, Bettina;Jarius, Sven;Meinck, Hans-Michael
目的：描述一种新的、独特的强直性和肌阵挛(PERM)的进行性脑脊髓炎(PERM)变异型，该变异型与针对神经元表面Kv4.2钾通道调节亚单位二肽基肽酶样蛋白6(DPPX)的抗体相关。以表达DPPX的HEK293细胞为基础的重组间接免疫荧光法用于检测哺乳动物组织中的DPPX抗体。结果：所有患者都表现出明显的症状，包括眼球运动障碍、明显的小脑性共济失调和躯干僵硬。其他症状包括痛觉过敏、神经性瘙痒和胃肠道症状。症状开始时很隐蔽，进展缓慢。所有患者均有炎性脑脊液特征，伴有轻度的细胞增多和鞘内免疫球蛋白G合成。在患者血清和脑脊液中检测到高滴度的DPPX抗体，特异性抗体指数提示鞘内合成DPPX抗体。免疫治疗的反应良好，但可能需要持续和积极的治疗。结论：这些病例突出了PERM和抗神经元抗体的扩谱。DPPX抗体检测应该被考虑在获得性脑功能亢进、小脑性共济失调和僵硬患者的诊断工作中，因为这些患者可能从免疫治疗中受益。需要进一步的研究来阐明与DPPX抗体相关的整个临床谱系及其在发病机制中的作用。
Objective:To describe a novel and distinct variant of progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with antibodies directed against dipeptidyl peptidase-like protein 6 (DPPX), a regulatory subunit of the Kv4.2 potassium channels on the surface of neurons.Methods:Case series describing the clinical, paraclinical, and serologic features of 3 patients with PERM. A recombinant, cell-based indirect immunofluorescence assay with DPPX-expressing HEK293 cells was used to detect DPPX antibodies in conjunction with mammalian tissues.Results:All patients presented with a distinct syndrome involving hyperekplexia, prominent cerebellar ataxia with marked eye movement disorder, and trunk stiffness of variable intensity. Additional symptoms comprised allodynia, neurogenic pruritus, and gastrointestinal symptoms. Symptoms began insidiously and progressed slowly. An inflammatory CSF profile with mild pleocytosis and intrathecal immunoglobulin G synthesis was found in all patients. High DPPX antibody titers were detected in the patients' serum and CSF, with specific antibody indices suggestive of intrathecal synthesis of DPPX antibodies. Response to immunotherapy was good, but constant and aggressive treatment may be required.Conclusion:These cases highlight the expanding spectrum of both PERM and anti-neuronal antibodies. Testing for DPPX antibodies should be considered in the diagnostic workup of patients with acquired hyperekplexia, cerebellar ataxia, and stiffness, because such patients might benefit from immunotherapy. Further studies are needed to elucidate both the entire clinical spectrum associated with DPPX antibodies and their role in pathogenesis.