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Review
. 2024 Apr;271(4):1747-1766.
doi: 10.1007/s00415-024-12189-4. Epub 2024 Jan 29.

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

Er-Chuang Li #  1 , Qi-Lun Lai #  2 , Meng-Ting Cai  3 , Gao-Li Fang  4 , Wei Fang  5 , Yang Zheng  6 , Ye Du  7 , Bing-Qing Du  3 , Chun-Hong Shen  3 , Song Qiao  2 , Mei-Ping Ding  8 , Yin-Xi Zhang  9
Affiliations
Review

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

Er-Chuang Li et al. J Neurol. 2024 Apr.

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.

Keywords: Biopsy; CLIPPERS; Corticosteroid; Neuroinflammation; Perivascular enhancement; Pontocerebellar involvement.

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References

    1. Pittock SJ, Debruyne J, Krecke KN, Giannini C, van den Ameele J, De Herdt V, McKeon A, Fealey RD, Weinshenker BG, Aksamit AJ, Krueger BR, Shuster EA, Keegan BM (2010) Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain 133(9):2626–2634. https://doi.org/10.1093/brain/awq164 - DOI - PubMed
    1. Simon NG, Parratt JD, Barnett MH, Buckland ME, Gupta R, Hayes MW, Masters LT, Reddel SW (2012) Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). J Neurol Neurosurg Psychiatry 83(1):15–22. https://doi.org/10.1136/jnnp-2011-301054 - DOI - PubMed
    1. Taieb G, Duflos C, Renard D, Audoin B, Kaphan E, Pelletier J, Limousin N, Tranchant C, Kremer S, de Sèze J, Lefaucheur R, Maltête D, Brassat D, Clanet M, Desbordes P, Thouvenot E, Magy L, Vincent T, Faillie JL, de Champfleur N, Castelnovo G, Eimer S, Branger DF, Uro-Coste E, Labauge P (2012) Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients. Arch Neurol 69(7):847–855. https://doi.org/10.1001/archneurol.2012.122 - DOI - PubMed
    1. Tobin WO, Guo Y, Krecke KN, Parisi JE, Lucchinetti CF, Pittock SJ, Mandrekar J, Dubey D, Debruyne J, Keegan BM (2017) Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain 140(9):2415–2425. https://doi.org/10.1093/brain/awx200 - DOI - PubMed
    1. Al-Chalabi M, DelCimmuto NR, Beran A, Devarasetty PP, Mhanna A, Mahfooz N, Sheikh A (2022) Clinical characteristics, management, and outcomes of CLIPPERS: a comprehensive systematic review of 140 patients from 100 studies. Mult Scler Relat Disord 68:104112. https://doi.org/10.1016/j.msard.2022.104112 - DOI - PubMed

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