Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients

Arch Neurol. 2012 Jul;69(7):847-55. doi: 10.1001/archneurol.2012.122.

Abstract

Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease.

Objective: To describe the disease course of CLIPPERS.

Design: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS.

Setting: Academic research.

Patients: Twelve patients with CLIPPERS.

Main outcome measures: The therapeutic management of CLIPPERS was evaluated.

Results: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy.

Conclusions: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Antigens, CD / metabolism
  • Cerebral Ventricles / pathology*
  • Disability Evaluation
  • Encephalitis / cerebrospinal fluid
  • Encephalitis / drug therapy*
  • Encephalitis / pathology*
  • Female
  • Gadolinium
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Pons / pathology*
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Antigens, CD
  • Immunosuppressive Agents
  • Gadolinium