Highlights
- •This is the largest systemic review on CLIPPERS including 100 case reports/series generating 140 patients.
- •CLIPPERS is more common in males with a mean age of 46 and ataxia was the most common symptom.
- •Mortality was worse in the malignancies-associated CLIPPERS cases and those who experienced relapses.
- •Steroids duration treatment in the acute phase was shorter in patients who experienced relapses.
- •Azathioprine was the most common steroids sparing agent in the maintenance therapy.
Abstract
Introduction
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.
Methods
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.
Results
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.
Conclusion
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.
Keywords
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Article info
Publication history
Published online: August 17, 2022
Accepted:
August 12,
2022
Received in revised form:
August 11,
2022
Received:
April 26,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
