Need for prolonged immunosupressive therapy in CLIPPERS-a case report

Abstract

BackgroundChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was first described in 2010 by Pittock and colleagues. All reported patients presented with diplopia and gait ataxia and had similar typical MRI findings with punctuate gadolinium enhancement of the pons. Alternative diagnoses were excluded by means of laboratory, radiological and histological tests. All patients were successfully treated with steroids. We present a case in which the steroid therapy was switched to long term immunosuppressive therapy, leading to several severe side-effects, but sustained clinical improvement.Case presentationA 63-year-old male presented with sub-acute diplopia and progressive gait ataxia. During admission his neurological condition worsened and he developed multiple cranial nerve deficits, paraparesis and urine retention. MRI-findings were remarkable with punctuate enhancement with gadolinium of the pons. Cerebrospinal fluid only showed elevated protein levels and all other additional investigations were normal. The probable diagnosis of CLIPPERS was made and intravenous corticosteroids were administered. This led to rapid clinical recovery and decreased enhancement on the MRI-scan. Long-term oral immunosuppressive therapy was started. One-and-a-half year later our patient has no recurrence of neurological symptoms, however due to the side effects of the immunosuppressive therapy he was readmitted several times.ConclusionCLIPPERS presents with distinctive clinical and MRI-findings and may be diagnosed after excluding other differential diagnoses. Patients are treated with corticosteroids with good clinical results. Since short term glucocorticoid treatment results into relapse of the disease, longer term immunosuppressive therapy appears to be mandatory for sustained improvement, although accompanied by severe side effects.

CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders

“…Clinical manifestations may be heterogeneous, multi‐faceted and variable in individual cases, but comprise essentially the following. Commonly prominent symptoms related to multi‐locular brainstem including cranial nerve and cerebellar involvement, which may present in various combinations or rarely in isolation (e.g. ataxia, dysarthria, oculomotor abnormalities, tingling of the face, vertigo) ; and Possible additional features such as: (i) symptoms referable to long tract affections and/or a spinal cord syndrome (e.g. pyramidal tract signs, spasticity, para‐/tetraparesis, altered limb superficial and deep sensation, sphincteric dysfunction) ; (ii) pseudobulbar affect (pathological crying and laugther) ; (iii) cognitive dysfunctions (e.g.…”

“…ataxia, dysarthria, oculomotor abnormalities, tingling of the face, vertigo) ; and Possible additional features such as: (i) symptoms referable to long tract affections and/or a spinal cord syndrome (e.g. pyramidal tract signs, spasticity, para‐/tetraparesis, altered limb superficial and deep sensation, sphincteric dysfunction) ; (ii) pseudobulbar affect (pathological crying and laugther) ; (iii) cognitive dysfunctions (e.g. mnestic deficits, dysexecutive syndrome) ; presumably also (iv) headaches and abnormal fatigue .…”

“…Extensive work‐ups were performed by virtually all study groups (e.g. [1,2,7,10,12,17,22,25,27]), and included assessments for: Complete blood count, routine blood chemistry, C‐reactive protein, erythrocyte sedimentation rate Autoantibodies and markers of vasculitis: anti‐nuclear antibodies (ANA), extractable nuclear antigens (ENA), p‐/c‐anti‐neutrophil cytoplasmic antibodies (ANCA), dsDNA antibodies, anti‐phospholipid antibodies, aquaporin‐4 antibodies, anti‐ganglioside antibodies (e.g. anti‐GQ1b antibodies), rheumatoid factor, circulating immune complexes, cryoglobulins Onconeuronal antibodies/paraneoplastic antibodies (targeting intracellular antigens), e.g.…”

“…Next to MRI of the brain and the spinal cord, various additional imaging investigations have been performed in CLIPPERS patients and usually revealed no seminal findings. The examinations included chest X‐rays, computerized tomography (CT) scans of the chest, abdomen and pelvis , whole‐body positron emission tomography (PET) and fluorodeoxyglucose (FDG)‐PET/CT scans , and brain PET scans . In some patients biopsies of tissues apart from the CNS (e.g.…”

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

“…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).…”