Relapsing-remitting chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids syndrome in association with P/Q-type voltage-gated calcium channel antibody.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is an encephalomyelitis with typical magnetic resonance imaging (MRI) features; curvilinear peppering lesions in the region of pons and cerebellum.[1] We present a case of CLIPPERS syndrome which depicts a potential association with P/Q-type voltage-gated calcium channel (VGCC) antibody.

A 57-year-old African-American female presented for the evaluation of recurrent episodes of vertigo and ataxia. The patient had her first episode of vertigo, ataxia, and diplopia, 2 years prior when she presented to an outside hospital. Neurological examination at that time was consistent with the right abducens nerve palsy and gait ataxia. MRI of the brain showed T2/fluid-attenuated inversion recovery hyperintensity in the region of the pons. She received 1 g of intravenous methylprednisolone for 5 days, followed by oral prednisone taper with a complete resolution of contrast enhancement and clinical symptoms. She had the second episode 8 months later, with MRI of the brain showing contrast enhancement in the region of the brain stem and cerebellum. This time, she again had a dramatic response to steroids. Two days before her current presentation to our hospital, she noticed recurrence of her typical symptoms: vertigo and ataxia. Her examination was significant for gait ataxia, diffuse hyperreflexia, and bilaterally positive Hoffman's sign. MRI of the brain and spinal cord was remarkable for curvilinear-enhancing lesions in the cerebellar hemispheres, multiple punctate-enhancing foci in the cerebral hemispheres, right cerebral peduncle, internal capsules, left putamen, anterior commissure [Figure 1a–d], and heterogeneously enhancing area within the cervicomedullary junction [Figure 1e and f], consistent with the diagnosis of CLIPPERS syndrome. Cerebrospinal fluid (CSF) studies were remarkable for 14 lymphocytes in the CSF, with 33 mg/dL protein and normal glucose. Other CSF studies including protein, glucose, oligoclonal bands, angiotensin-converting enzyme, viral polymerase chain reactions, aquaporin-4 antibody, and CSF flow cytometry/cytology were unremarkable. Serology was remarkable for elevated P/Q-type VGCC antibody at 0.3 nmol/L. During the course of hospitalization, no limb or bulbar weakness suggestive of Lambert–Eaton myasthenic syndrome was detected, and as such electrophysiological studies were deferred. Computed tomography (CT) of the chest, abdomen, and pelvis was unremarkable for lymphadenopathy or underlying malignancy. MR spectroscopy was performed that demonstrated an elevated lactate and lipid peaks that upon review by radiology were not felt to represent malignancy. She was treated with 3 days of 1 g intravenous methylprednisolone and had complete resolution of her symptoms. She was started on mycophenolate and continued to be relapse-free on the last clinical follow-up 8 months after initial presentation to our hospital. Given the findings of a paraneoplastic antibody, surveillance screening for malignancy with CT of the chest, abdomen, pelvis, and interval follow-up of MRI is planned.

Figure 1

Curvilinear-enhancing areas of perivascular pattern (a-d) involving the cerebellar hemispheres centered in the dentate nuclei and multiple punctate-enhancing foci scattered in cerebral hemispheres. Heterogeneous area of enhancement (e) at the cervicomedullary junction associated with T2/short-tau inversion recovery hyperintensity (f)

P/Q-type VGCC antibodies have been described in association with paraneoplastic cerebellar degeneration, but a case of CLIPPERS syndrome with P/Q-type VGCC antibody has not been reported.[2] Studies have shown binding of P-type VGCC antibodies not only to the cerebellar dendrites and soma but also to various regions of the brainstem and cerebral cortex,[3] which could potentially explain brainstem and supratentorial lesions in patients with CLIPPERS syndrome. Pathogenesis of CLIPPERS syndrome still remains unclear, though there is some evidence from case series demonstrating patients developing CLIPPERS preceding or following a diagnosis of systemic or central nervous system lymphoma.[45] Our case supports further evaluation of the role of P/Q-type VGCC antibodies in this rare encephalomyelitis.

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