Objective:

Assess clinical course, treatment response and outcome of all cases of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) at the University of Florida (UF).

Background:

CLIPPERS is a rare central nervous system neuroinflammatory disorder with characteristic imaging (punctate, curvilinear pontine and rhombencephalic contrast enhancement) and neuropathological (dense perivascular CD4+ T-cell predominant inflammatory cell infiltrates) findings with clinical and radiographic response to corticosteroids. There is only limited data from small case series regarding the clinical course and overall responsiveness to steroid-sparing medications.

Design/Methods:

This is a single-center retrospective case series of all cases of CLIPPERS at UF between October 1, 2015, and June 30, 2023 identified via the SlicerDicer data extraction tool (Epic Systems Corporation, Verona, WI, USA) and our institution’s clinical databases.

Results:

We identified 9 patients with CLIPPERS (median age 65 [23-85]; 2/9 [22%] female). Median age at disease onset was 63 (22-80). All patients showed characteristic pontine/rhombencephalic T2/FLAIR hyperintensities and contrast enhancement. 4/9 (44.4%) underwent a brain biopsy with perivascular CD4+ T-cell predominant inflammatory cell infiltrates. All patients received corticosteroids with associated clinical improvement. Most frequently utilized steroid-sparing medications were mycophenolate mofetil (MMF) 500-1500 mg twice daily (n=5; 4 with available follow-up data), methotrexate (MTX) 15-25 mg weekly (n=4) and azathioprine (n=2) 50-150 mg daily each with observed treatment failure in 50% each. Treatment failure was also observed in patients treated with cyclophosphamide (n=1)  and interferon beta-1a (n=1). Rituximab therapy was associated with stability in 1 case (treatment duration of 1 year). 3/9 (33%) patients had an unfavorable outcome (3 deaths).

Conclusions:

None of the utilized steroid-sparing therapies appear to have good efficacy in CLIPPERS with best data for MTX, MMF and AZA with disease stability in 50% of cases. The outcome of the disease may frequently be unfavorable (33% fatal in our case series).