Clinical characteristics, management, and outcomes of CLIPPERS: A comprehensive systematic review of 140 patients from 100 studies
Mustafa Al-Chalabi1, Nicholas Delcimmuto1, Ajaz Sheikh2
1Department of Neurology, University of Toledo, 2ProMedica Neurosciences Center
Objective:
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Background:
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.
Design/Methods:
A comprehensive search of PubMed and Web of Science databases was conducted from inception until January 15, 2022, was conducted. 
Results:
A total of 140 patients with CLIPPERS were included (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.  16% of 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 chronic steroid dosing (less than 20 mg/d versus greater than 20 mg/d) there was no significant modification in the risk of relapse
Conclusions:
Diagnosis of CLIPPERS is often challenging, and delays in diagnosis and treatment can lead to unfavorable outcomes. These patients should be screened for associated malignancies, especially hematological malignancies. Malignancy associated cases tend to have worse outcomes. The relapse rate is relatively high and 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
10.1212/WNL.0000000000202260