复发性类固醇激素治疗有效的慢性淋巴细胞性炎症伴脑桥血管周围强化症一例临床病理分析

Clinical and pathological analysis of recurrent chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids：one case report

目的：报道1例病程长达9年、早期临床和影像学表现不典型、后期经病理证实的类固醇激素治疗有效的慢性淋巴细胞性炎症伴脑桥血管周围强化症（ CLIPPERS）患者，以提高对本类疾病谱的认识。方法回顾性分析1例病程长达9年、多次复发缓解、阶梯样加重、最终经病理证实的CLIPPERS患者的临床特征、影像学表现、实验室检查、病理特点以及治疗和预后。结果患者总病程9年，临床5次复发缓解，早期临床和影像学表现不典型：首次发作临床表现为发热、头痛、意识障碍、抽搐发作，此后发作伴共济失调、视物模糊及肢体无力。2006—2009年患者头颅MRI表现为：以幕上脑白质受累为主、同时累及脑桥和小脑的颅内多发异常信号，增强扫描后呈斑片状异常强化，激素治疗后临床和影像学表现均明显改善。本次复发表现为肢体无力、视物模糊、饮水呛咳和构音欠清。体检发现：高级智能减退，多脑神经损害及双侧锥体束征。头颅MRI表现为：颅内以脑桥、小脑为主同时累及幕上白质的多发病变，增强扫描呈“胡椒粉”样斑点状强化，部分强化灶融合，脑萎缩。脑组织活体组织检查病理显示血管周围以T淋巴细胞为主的炎性浸润，未见血管壁坏死，未发现异型淋巴细胞。符合CLIPPERS影像学及组织病理学特点，激素冲击治疗后患者临床症状和影像学表现均明显改善。结论 CLIPPERS临床及影像学均可表现异质性，可呈复发缓解病程，特征性的病理改变是诊断“金标准”。目前其疾病本质尚不明确，但多次复发可继发脑萎缩变性，并存在向中枢神经系统淋巴瘤转化的风险。早期类固醇激素治疗有效，早期、长期坚持免疫治疗可能预防复发、改善预后。

Objective To report a case presented with atypical clinical and radiological appearance in the early stage and finally pathologically confirmed as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids （ CLIPPERS） , aiming to improve the understanding of the disorder. Methods The clinical, imaging, laboratory and pathological features as well as treatment and prognosis of a pathologically confirmed CLIPPERS patient with repeated relapsing-remitting course and stepwise progression in nine years were retrospectively analyzed. Results There were five relapsing-remitting processes in total clinical course of nine years. The clinical and radiological appearance was atypical in the early stage. At the first attack, the patient presented with fever, headache, altered consciousness and epileptic seizure. In the following courses, the patient presented with ataxia, blurred vision and limb weakness. Brain MRI （2006-2009） showed multiple abnormal signals including supratentorial white matter, pons and cerebellum with patchy gadolinium enhancement. Treatment with steroids resulted in a favorable clinical and radiological improvement. The symptoms of this attack included＆amp;nbsp;limb weakness, blurred vision, dysdipsia and dysarthria. Physical examination showed cognitive dysfunction, multiple cranial nerves injuries and bilateral pyramidal signs. Brain MRI showed multiple abnormal signals involved pons and cerebellum predominantly as well as supratentorial white matter with punctate gadolinium enhancement peppering the pons and cerebellum. A characteristic predominantly T lymphocytic perivascular infiltration was seen on brain biopsy. Both the imaging and histological findings were consistent with the CLIPPERS features. High-dose steroids treatment was given and obvious clinical and radiological improvements were observed. After discharge, steroids were reduced slowly combined with the use of immunosuppressant to avoid relapse of the disorder. Conclusions There is heterogeneity in clinical manifestations of CLIPPERS with repeated relapsing-remitting course and imaging presentations are sometimes atypical in the early stage, which leads to the misdiagonsis and missed diagnosis. Distinctive pathology is the “gold standard” for definite diagnosis. The nosological position of CLIPPERS is still unclear. Repeated relapse-remitting leads to secondary cerebral atrophy and degeneration, with the risk of progressing to primary central nervous system lymphoma. Early and vigorous steroids treatment with continuing maintenance immunotherapy results in the decreased relapse and best long-term prognosis. The neurologist should strengthen the understanding of CLIPPERS for early correct diagnosis and treatment aiming to reduce the functional disability.