CLIPPERS

Morten Blaabjerg MD PhD (Dr. Blaabjerg of Odense University has no relevant financial relationships to disclose.)
Daniel Kondziella MD PhD (Dr. Kondziella of Copenhagen University Hospital has no financial relationships to disclose.)
Anthony T Reder MD, editor. (Dr. Reder of the University of Chicago served on advisory boards and as a consultant for Bayer, Biogen Idec, Caremark Rx, Genentech, Genzyme, Novartis, Malinkrodt, Serono, and Teva-Marion.)
Originally released September 12, 2012; last updated November 28, 2017; expires November 28, 2020

This article includes discussion of CLIPPERS and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory condition of unknown etiology, primarily involving the brainstem and cerebellum. Symptoms of CLIPPERS include subacute onset of brainstem symptoms--most prominently, ataxia, diplopia, dysarthria, and altered facial sensation. The core radiological features are punctate or curvilinear perivascular gadolinium enhancement, typically in the pons and adjacent cerebellum. Neuropathological examination of affected areas reveals a perivascular lymphocytic inflammation with predominant CD4+ T cells. Clinical and radiological features respond to high-dose corticosteroid treatment, but continuous oral corticosteroid treatment and steroid-sparing agents are needed to prevent relapses and to reduce the risk for subsequent parenchymal atrophy and chronic ataxia. The differential diagnosis for CLIPPERS is broad, and a careful workup is needed.

Key points

 

• CLIPPERS is a relapsing subacute brainstem syndrome presenting with symptoms such as ataxia, diplopia, dysarthria, and altered facial sensation.

 

MRI shows punctate or curvilinear gadolinium enhancement in the pons and adjacent cerebellum. Lesions may extend into the basal ganglia or the cervico-thoracal medulla.

 

• Neuropathological examination of affected regions shows a perivascular lymphocytic inflammation that may involve both white and grey matter, with a CD4+ T cell predominance.

 

• No biomarker is available for CLIPPERS, and the differential diagnoses is broad, requiring a careful workup of alternative causes. Proposed diagnostic criteria are helpful in differentiating CLIPPERS from CLIPPERS mimics and, in typical cases, allow for diagnosis without brain biopsy.

 

• Both clinical symptoms and MRI abnormalities respond well to high-dose intravenous methylprednisolone, but continuous oral corticosteroid treatment and steroid-sparing agents are often needed to prevent relapses.

Historical note and terminology

CLIPPERS was initially described by Dr. Pittock and colleagues in 2010, based on a case series of 8 patients with similar clinical, radiological, and pathological features and a robust response to corticosteroid treatment (Pittock et al 2010). Following the original description, a number of smaller and larger case series and case reports described similar patients, expanding the clinical and pathological features (Biotti et al 2011; Gabilondo et al 2011; Jones et al 2011; Kastrup et al 2011; Simon et al 2012; Taieb et al 2012; Tohge et al 2012; Sempere et al 2013; Kerrn-Jespersen et al 2014). Patients with alternative diagnoses initially suspected to have CLIPPERS have also been reported. These include CNS lymphoma (De Graff et al 2013; Lin et al 2014), systemic T cell lymphoma (Nakamura et al 2016), Hodgkins lymphoma (Mashima et al 2015), primary cerebral angiitis (Buttmann et al 2013), MOG-associated disease (Symmonds et al 2015), multiple sclerosis (Ortega et al 2012), and chronic hepatitis B infection (Weng et al 2015). Such cases have led to discussion of whether CLIPPERS represents a unique condition or merely a group of disorders that share the early features of ataxia, brainstem symptoms, and pontine perivascular contrast-enhancement on MRI. A large case series of 35 patients with a presumed diagnosis of CLIPPERS (of whom 23 were ultimately diagnosed with this disorder) has led to proposed diagnostic criteria for the differentiation of CLIPPERS from its mimics (Tobin et al 2017).

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