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Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies

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Abstract

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions (“salt-and-pepper” appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-d-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

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Copyright 2014, with permission from Elsevier. CLIPPERS chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, MRI magnetic resonance imaging, T1WI T1-weighted imaging, T2WI T2-weighted imaging

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Data availability

Data sharing not applicable to this article as no new datasets were generated during the current study. The data that support the findings of this study were derived from public domain resources as referenced.

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  1. Er-Chuang Li and Qi-Lun Lai contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Taikang Ningbo Hospital, Ningbo, 315042, China

    Er-Chuang Li

  2. Department of Neurology, Zhejiang Hospital, Hangzhou, 310013, China

    Qi-Lun Lai & Song Qiao

  3. Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, China

    Meng-Ting Cai, Bing-Qing Du, Chun-Hong Shen, Mei-Ping Ding & Yin-Xi Zhang

  4. Department of Neurology, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital, Hangzhou, 310003, China

    Gao-Li Fang

  5. Department of Neurology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China

    Wei Fang

  6. Department of Neurology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China

    Yang Zheng

  7. Department of Neurology, Shaoxing People’s Hospital, Shaoxing, 312000, China

    Ye Du

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Contributions

Er-Chuang Li: conceptualization, data curation, formal analysis, investigation, writing-original draft, writing—review and editing. Qi-Lun Lai: conceptualization, data curation, formal analysis, investigation, writing—original draft, writing—review and editing. Meng-Ting Cai: data curation, formal analysis, investigation, writing—review and editing. Gao-Li Fang: data curation, formal analysis, investigation, writing—review and editing. Wei Fang: data curation, formal analysis, investigation, writing—review and editing. Yang Zheng: data curation, formal analysis, investigation, writing—review and editing. Ye Du: data curation, formal analysis, investigation, writing—review and editing. Bing-Qing Du: data curation, formal analysis, investigation, writing—review and editing. Chun-Hong Shen: data curation, formal analysis, investigation, writing—review and editing. Song Qiao: data curation, formal analysis, investigation, writing—review and editing. Mei-Ping Ding: conceptualization, data curation, formal analysis, investigation, supervision, validation, writing—review and editing. Yin-Xi Zhang: conceptualization, data curation, formal analysis, investigation, supervision, validation, writing—review and editing.

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Correspondence to Mei-Ping Ding or Yin-Xi Zhang.

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Li, EC., Lai, QL., Cai, MT. et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies. J Neurol 271, 1747–1766 (2024). https://doi.org/10.1007/s00415-024-12189-4

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