Al-Chalabi Mustafa, DelCimmuto Nicholas R, Beran Azizullah, Devarasetty Pratyush Pavan, Mhanna Asmaa, Mahfooz Naeem, Sheikh Ajaz
Department of Neurology, University of Toledo, 2130W Central Ave., Toledo, OH 43606, United States.
College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United States.
Mult Scler Relat Disord. 2022 Dec;68:104112. doi: 10.1016/j.msard.2022.104112. Epub 2022 Aug 18.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder of the central nervous system, characterized by symptoms referable to the brainstem and cerebellum such as, diplopia, gait ataxia and cerebellar dysarthria. The features and outcomes of CLIPPERS remains uncertain. we conducted this comprehensive systematic review to summarize all the existing studies that described CLIPPERS in the literature and to provide a quantitative assessment on the clinical characteristics, management, and outcomes of this rare syndrome.
A comprehensive search of PubMed and Web of Science databases was conducted from inception until January 15, 2022, was conducted. We only included the cases that clearly reported probable or definite diagnosis of CLIPPERS based on Taieb et al.'s criteria. The quality of the included studies was assessed using the JBI Critical Appraisal Tool. Descriptive statistics were performed to analyze the studies. Data were expressed as mean and standard deviation (SD) for continuous variables and proportions for categorical variables.
We identified 100 case reports and series including a total of 140 patients with CLIPPERS (mean age: 46±18 years and males were 60%). The average follow-up duration was 32.27±57.8 months. Ataxia was the most common presenting symptom. Sixteen percent of the cases were associated with malignancy, mostly hematologic malignancies. The overall relapse rate was 59.2%, and the duration of steroid therapy was considerably shorter in the relapsed cases than in the non-relapsed (mean 6.19±7.9 vs. 10.14±12.1 days, respectively, P = 0.04). The overall mortality rate was 10%, but mortality in patients with malignancy was 30% and it was 12% in patients with relapses. In the case of steroid dosing (less than 20 mg/d versus greater than 20 mg/d) there was no significant modification in the risk of relapse.
CLIPPERS is a rare clinical syndrome that affects mainly middle-aged males. Diagnosis of CLIPPERS is often challenging, and delays in diagnosis and treatment can lead to unfavorable outcomes. Therefore, neurologists should maintain a high index of suspicion for CLIPPERS in any patient presenting with symptoms and signs referrable to the brainstem. These patients should be screened for associated malignancies, especially hematological malignancies. The cases associated with malignancy tend to have worse outcomes. The relapse rate is relatively high. The relapse rate may be associated with worse mortality. Based on our findings, we recommend that CLIPPERS be treated with high-dose steroid therapy for at least ten days during the acute phase with a very slow taper. Prospective studies with a larger sample size are needed to validate our findings and guide the clinical care of these patients.
类固醇反应性桥脑周围血管强化慢性淋巴细胞性炎症（CLIPPERS）是一种罕见的中枢神经系统炎性疾病，其特征为出现与脑干和小脑相关的症状，如复视、步态共济失调和小脑性构音障碍。CLIPPERS的特征及预后仍不明确。我们进行了这项全面的系统评价，以总结文献中所有描述CLIPPERS的现有研究，并对这种罕见综合征的临床特征、治疗及预后进行定量评估。
对PubMed和Web of Science数据库从建库至2022年1月15日进行全面检索。我们仅纳入了根据Taieb等人的标准明确报告可能或确诊为CLIPPERS的病例。使用JBI批判性评价工具评估纳入研究的质量。进行描述性统计分析这些研究。连续变量数据以均值和标准差（SD）表示，分类变量数据以比例表示。
我们确定了100篇病例报告和系列研究，共纳入140例CLIPPERS患者（平均年龄：46±18岁，男性占60%）。平均随访时间为32.27±57.8个月。共济失调是最常见的首发症状。16%的病例与恶性肿瘤相关，主要是血液系统恶性肿瘤。总体复发率为59.2%，复发患者的类固醇治疗持续时间明显短于未复发患者（分别为平均6.19±7.9天和10.14±12.1天，P = 0.04）。总体死亡率为10%，但恶性肿瘤患者的死亡率为30%，复发患者的死亡率为12%。在类固醇给药剂量方面（小于20mg/d与大于20mg/d），复发风险无显著差异。
CLIPPERS是一种罕见的临床综合征，主要影响中年男性。CLIPPERS的诊断通常具有挑战性；诊断和治疗延迟会导致不良预后。因此，对于任何出现与脑干相关症状和体征的患者，神经科医生应高度怀疑CLIPPERS。这些患者应筛查相关恶性肿瘤，尤其是血液系统恶性肿瘤。与恶性肿瘤相关的病例往往预后较差。复发率相对较高。复发率可能与更差的死亡率相关。根据我们的研究结果，我们建议CLIPPERS患者在急性期接受大剂量类固醇治疗至少十天，并非常缓慢地减量。需要进行更大样本量的前瞻性研究来验证我们的研究结果并指导这些患者的临床护理。
