Autoantibodies: disease markers
Oct. 25, 2023
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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.
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.
• 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.
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 (02; 11; 12; 14; 27; Taieb et al 2012; 34; 25; 15). Patients with alternative diagnoses initially suspected to have CLIPPERS have also been reported. These include CNS lymphoma (De Graff et al 2013; 18), systemic T cell lymphoma (21), Hodgkins lymphoma (19), primary cerebral angiitis (05), anti-MOG-associated disease (28), multiple sclerosis (22), and chronic hepatitis B infection (35). 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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