Balint Bettina, Jarius Sven, Nagel Simon, Haberkorn Uwe, Probst Christian, Blöcker Inga Madeleine, Bahtz Ramona, Komorowski Lars, Stöcker Winfried, Kastrup Andreas, Kuthe Martin, Meinck Hans-Michael
From the Departments of Neurology (B.B., S.J., S.N., H.-M.M.) and Nuclear Medicine (U.H.), University of Heidelberg; Institute for Experimental Immunology (C.P., I.M.B., R.B., L.K., W.S.), Euroimmun, Lübeck; Department of Neurology (A.K.), Klinikum Bremen Ost; and Department of Neurology (M.K.), Community Hospital Herdecke, Germany.
Neurology. 2014 Apr 29;82(17):1521-8. doi: 10.1212/WNL.0000000000000372. Epub 2014 Apr 2.
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.
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.
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.
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.
描述一种新型且独特的进行性脑脊髓炎伴强直和肌阵挛（PERM）变异型，其与针对二肽基肽酶样蛋白6（DPPX）的抗体相关，DPPX是神经元表面Kv4.2钾通道的调节亚基。
病例系列描述了3例PERM患者的临床、副临床和血清学特征。使用表达DPPX的HEK293细胞进行重组细胞间接免疫荧光测定，结合哺乳动物组织检测DPPX抗体。
所有患者均表现出一种独特的综合征，包括惊吓反射亢进、伴有明显眼球运动障碍的显著小脑共济失调以及不同程度的躯干僵硬。其他症状包括痛觉过敏、神经性瘙痒和胃肠道症状。症状隐匿起病且进展缓慢。所有患者脑脊液检查均显示炎症特征，有轻度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DPPX抗体滴度，特异性抗体指数提示DPPX抗体鞘内合成。免疫治疗反应良好，但可能需要持续且积极的治疗。
这些病例凸显了PERM和抗神经元抗体谱的不断扩大。对于获得性惊吓反射亢进、小脑共济失调和僵硬的患者，在诊断检查中应考虑检测DPPX抗体，因为这类患者可能从免疫治疗中获益。需要进一步研究以阐明与DPPX抗体相关的整个临床谱及其在发病机制中的作用。
