Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS)

Abstract

Chronic lymphocytic inflammation with pontine perivascular enhancement re-sponsive to steroids (CLIPPERS) is an inflammatory disease of the CNS first described by Pittock et al in 2010 (1). Patients usually present with subacute ataxia, diplopia, and a range of other clinical features related to brainstem involvement. Brain magnetic resonance imaging (MRI) shows ''punctate'' and/or ''curvilinear'' gadolinium enhancement peppering the pons and extending variably into the brachium pontis, cerebellum, and adjacent CNS structures. An extensive laboratory, radiologic, and pathologic analysis is essential to exclude other diseases (2). Patients have favorable clinical and radiologic response to steroids requiring chronic immunosuppression (2); otherwise, without a specific treatment, progression seems to be relapsing-remitting (3). Lesion biopsies have revealed perivascular CD4-dominated T-cell or lymphohistiocytic infiltrates and activated microglia, involving predominantly the white matter (2). The pathogenesis and pathophysiology of CLIPPERS are unknown. Herein, we present the first case of CLIPPERS with FIGURE 1. Magnetic resonance imaging (MRI). Axial (A, B) and coronal (C) T2-weighted images show patchy areas of hyperintensity in the brainstem, middle cerebellar peduncles, and left deep cerebellar white matter. (D, E) After gadolinium injection, coronal T1-weighted images reveal multiple foci of linear and punctate enhancement peppering the brainstem, mainly at the pons, as well as in the left middle cerebellar peduncle and deep cerebellar white matter. (F) Two weeks after starting corticotherapy, follow-up MRI coronal T2 image shows a decrease in size and extent of lesions.

Widespread inflammation in CLIPPERS syndrome indicated by autopsy and ultra-high-field 7T MRI

“…Indeed, these efforts revealed contrast-enhancing lesions in supratentorial locations, supporting widespread inflammation in brain areas, in contrast to the only other autopsy report published recently. 19 The number of such contrast-enhancing lesions was, however, limited, which is likely due to the immunosuppressive treatment: MRI changes in CLIPPERS respond rapidly to immunosuppression. 1 , 3 , 20 , 21 Remarkably, when combining T1W and supratentorial T2*W images with a resolution as good as 0.08 mm 3 , we could show a vascular structure within most contrast-enhancing lesions.…”

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids with seizures and central pyrexia, in a patient requiring tracheal intubation and mechanical ventilation: A case report

“…On post-mortem, lesions were seen at different stages of evolution, suggesting a relapsing-remitting disease. 8 Epstein-Barr virus has been seen in several cases, including one which progressed to intracranial lymphoma. Other authors have hypothesised that CLIPPERS may be a pre-lymphoma condition and have emphasised the importance of continued follow-up to monitor long-term outcomes.…”

“…Intravenous Ig were given periodically over several months, but this did not appear to make a marked difference to the patient's recovery, in line with other literature. 8 Intensive neurological rehabilitation was required and is ongoing, 10 months from presentation. Swallowing difficulties have persisted and the patient has had recurrent aspiration pneumoniae.…”

Pseudo-Foster-Kennedy syndrome with optic nerve compression by the gyrus rectus

“…Recently, a postmortem analysis performed in a patient sharing all CLIPPERS features revealed the classical perivascular lymphohistiocytic infiltrates but also perivenular demyelinating lesions (as seen in acute disseminated encephalomyelitis). 5 Since perivenular demyelinating lesions were found in only one CLIPPERS patient, it is unlikely that CLIPPERS is a primary demyelinating disease. However, as suggested by the authors, CLIPPERS may induce immunization against MOG antigen.…”