CLIPPERS With Chronic Small Vessel Damage: More Overlap With Small Vessel Vasculitis?

Abstract

In 2010, Pittock et al (1) published a seminal report on an entity they entitled “Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).” After this, other reports of the entity quickly appeared (2–22) (Table). A recently presented abstract reviews several more unpublished non-English language cases (19). Despite this, most reports have emphasized neuroimaging or clinical features and neuropathologists may not be familiar with the syndrome. View this table: TABLE Detailed Review of Neuropathologic Features of CLIPPERS As discussed in commentaries by Kira (23), and Keegan and Pittock (24), the essential feature of the disease is seen on magnetic resonance imaging (MRI) scans. These show punctate and curvilinear gadolinium enhancement that “peppers” the pons; the enhancement is almost always symmetric (with only 1 of 8 asymmetric in the original series [1] and 1 asymmetric in a recent case report [17]). Signal abnormalities often extend into contiguous cerebellum, brainstem, or even thalami and cerebral cortex, as emphasized by others after the original report (3, 4, 10). Simon et al (10) even suggested a nomenclature modification from “pontine” to “pontocerebellar” to reflect the more widespread features. Clinically, patients present with fluctuating brainstem symptoms and show response to steroids, although it has become increasingly clear that relapses are frequent (8) and immunosuppressive therapy often needs to be prolonged; nonsteroidal drugs such as cyclophosphamide, azathioprine, or rituximab have been required (18, 19). Stereotypic neuroimaging features were felt from the initial report to obviate the need for brain biopsy (1), leading to fewer histologic than clinical/ neuroimaging descriptions of the syndrome (Table). Nevertheless, neuropathologic features of CLIPPERS, even when biopsied from nonpontine sites (Table), have been fairly uniform. Most cases have shown perivascular and parenchymal lymphocytic collections associated with macrophages, microglia, and occasionally plasma cells or neutrophils; true tight granulomas and demyelination …