Is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in children the same condition as in adults?

Abstract

This case series describes three children with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), an inflammatory condition characterized by a relapsing-remitting disease course responsive to steroids. The patients (two males, age 3y and 13y; one female, age 14y) presented with ataxia, dysarthria, and multiple cranial neuropathies. All patients demonstrated bilateral nodular lesions with contrast enhancement in the brainstem and cerebellum on magnetic resonance imaging, and perivascular lymphocytes and macrophages infiltrates on brain biopsies. Despite an initially good response to corticosteroids, all patients eventually became steroid-dependent or -resistant, with frequent relapses on maintenance immunosuppressive therapy. Natalizumab and intravenous immunoglobulin stopped neurological disease progression in Patient 1 but he died at 17 years from respiratory complications. Patient 2 went into remission on infliximab and intravenous methylprednisolone for several months but was then diagnosed with Epstein-Barr virus driven B-cell lymphoma 3 years after symptom onset. Patient 3 failed to respond to treatment and died 4 years after diagnosis. CLIPPERS disease in children is aggressive, with poor response to immunotherapy. Earlier use of newer immunotherapeutic agents such as natalizumab may be beneficial. Potential side effects need to be considered carefully. WHAT THIS PAPER ADDS: Paediatric chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) appears a more severe condition than previously reported in adults. Aggressive treatment before neuroaxonal loss may be required for a better outcome.