Department of Neurology, University Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.
J Neurol. 2011 Dec;258(12):2140-6. doi: 10.1007/s00415-011-6071-4. Epub 2011 May 10.
The aim of the study was to further determine the pathophysiology, clinical course, MRI-features and response to therapy of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), which has recently been proposed as a rare chronic inflammatory central nervous system disorder responsive to immunosuppressive therapy. Three patients with this rare entity underwent serial clinical and bimonthly MRI follow-up over a period of up to 16 months. Extensive laboratory work-up and brain biopsy were performed. Intravenous methylprednisolone or oral dexamethasone was administered as treatment, additionally cyclophosphamide in one patient. Clinically, diplopia, nystagmus, ataxia and facial paresthesia were the cardinal symptoms. Magnetic resonance imaging (MRI) disclosed patchy spot-like gadolinium enhancement in a "salt-and-pepper like appearance" in the pons, midbrain and cerebellum, in two cases with thalamic and in the other with spinal involvement. Brain biopsies demonstrated a predominantly angiocentric but also diffuse infiltration pattern by small mature lymphocytes. Treatment with steroids led to rapid clinical improvement and marked resolution of MRI lesions. As discontinuation of steroids led to clinical relapse, one patient was treated with a further course of steroids and the other with steroids and cyclophosphamide as immunosuppressive therapy. This led to stable remission with only mild clinical residue and normalization of MRI. Extensive laboratory and radiological work-up could not identify any other cause of the disease. Of note, in two cases a marked elevation of IgE in serum was found initially and throughout the course. CLIPPERS seems to be a distinct inflammatory central nervous system disorder. It shows characteristic MRI core features. Extrapontine involvement seems to be frequent. Histologically it is characterised by predominantly angiocentric infiltration by small mature lymphocytes. A pathogenetic relationship between the elevated IgE levels and the perivascular infiltrates can be presumed. It is responsive to immunosuppressive therapy and can require prolonged or maintenance treatment.
本研究旨在进一步确定慢性淋巴细胞性炎症伴桥脑血管周围强化对类固醇反应性（CLIPPERS）的病理生理学、临床过程、MRI 特征和对治疗的反应，最近提出该病是一种对免疫抑制治疗有反应的罕见慢性炎症性中枢神经系统疾病。3 例该罕见疾病患者接受了长达 16 个月的定期临床和每两个月一次的 MRI 随访。进行了广泛的实验室检查和脑活检。给予静脉甲基强的松龙或口服地塞米松治疗，1 例患者加用环磷酰胺。临床上，复视、眼球震颤、共济失调和面部感觉异常是主要症状。磁共振成像（MRI）显示桥脑、中脑和小脑呈斑点状、散在强化，呈“椒盐样外观”，2 例患者伴有丘脑受累，另 1 例伴有脊髓受累。脑活检显示小成熟淋巴细胞以血管中心性浸润为主，也有弥漫性浸润。类固醇治疗导致临床迅速改善和 MRI 病变明显消退。由于停用类固醇导致临床复发，1 例患者接受了另一轮类固醇治疗，另 1 例患者接受了类固醇和环磷酰胺免疫抑制治疗。这导致仅残留轻度临床症状和 MRI 正常的稳定缓解。广泛的实验室和影像学检查未能确定该疾病的任何其他病因。值得注意的是，2 例患者最初和整个病程中血清 IgE 明显升高。CLIPPERS 似乎是一种独特的炎症性中枢神经系统疾病。它具有特征性的 MRI 核心特征。延髓外受累似乎很常见。组织学上以小成熟淋巴细胞为主的血管中心性浸润为特征。可以推测 IgE 水平升高与血管周围浸润之间存在发病关系。它对免疫抑制治疗有反应，可能需要长期或维持治疗。
