A Case of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) in East Asia

Abstract

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIP-PERS) syndrome is a clinically and radiologically distinct pontine-predominant perivascular neuroinflammation showing T lymphocyte infiltration. It is assumed to have an autoimmune or other inflammatory mediated pathogenesis. We report the first known case of CLIPPERS in East Asia, characterized by multiple punctate enhancement of the brainstem extending to the bilateral posterior limb of the internal capsule and caudal to the spinal cord conus. The patient had elevated IgE levels and a history of allergies, suggesting that lesions may arise from neuroinflammation in response to T lymphocyte infiltration into perivascular spaces.

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

“…It can also be speculated that an allergic trigger factor may contribute to the evolution of the perivascular inflammation process. Elevated serum immunoglobulin (Ig)E levels, which were noted in several cases , may be seen in this context. Atopic disease and in particular atopic myelitis , pathological conditions presenting with elevated IgE levels in response to various environmental antigens, may offer clues to the link of elevated IgE and distinct forms of neuroinflammatory diseases such as CLIPPERS .…”

“…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 .…”

Horizontal eyeball akinesia as an initial manifestation of CLIPPERS

“…Considering the anatomic arrangement of small intra-axial veins of the central nervous system (CNS), the predominant involvement of brainstem structures might be related to a primary CNS venous inflammatory disorder. [14] Elevated levels of immunoglobulin IgE in serum were noted in several CLIPPERS cases, [2,15] suggesting that immediate and late allergic reactions may contribute to the pathogenesis of CLIPPERS. Interestingly, anti-tuberculous therapy was effective for CLIPPERS.…”

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

“…Salivary gland biopsy in the case reported by Biotti et al (11) was normal. Other unusual individual patients with otherwise radiographically typical CLIPPERS have manifested elevated IgE (4,12), peripheral nerve abnormalities on nerve conduction studies (12), multiple sclerosis with onset of CLIPPERS after withdrawal of drug therapies (15,21), temporal association with influenza vaccination (13), primary central nervous system lymphoma (9,17), or even glioma-like biopsy features (6). Kira (23) has questioned whether CLIPPERS is a single disease or a syndrome and Keegan made the critical point that until specific markers are identified for CLIPPERS, it may be impossible to answer the question (24).…”