Abstract
ObjectiveThe purpose of this paper is to report a patient with otherwise unexplained cerebellar ataxia with serum antibodies against contactin-associated protein-2 (CASPR-2) and provide a detailed description of the composition of cellular infiltrates in the cerebrospinal fluid (CSF) compared to the peripheral blood (PB). CASPR-2 antibodies strongly labeling axons of cerebellar granule neurons have recently been identified in sera from nine patients with otherwise unexplained progressive cerebellar ataxia with mild to severe cerebellar atrophy.DesignThis is a report of a single case.MethodsThe study methods used were neurologic examination, magnetic resonance imaging, fluorodeoxyglucose positron emisson tomography, lumbar puncture and multicolor flow-cytometry.ResultsA 23-year-old Caucasian male presented with a two-year history of a progressive cerebellar and brainstem syndrome. Magnetic resonance imaging (MRI) showed pronounced cerebellar atrophy, especially of the medial parts of the hemispheres and the vermis. Cerebral fluorodeoxyglucose positron emission tomography (FDG-PET) showed pronounced hypometabolism of the whole cerebellum. CASPR-2 antibodies were detected in the serum but not the CSF, and none of the staging and laboratory assessments revealed other causes of progressive cerebellar degeneration. Interestingly, flow-cytometry of the CSF as compared to the PB showed increased fractions of CD138+ plasma cells as well as human leukocyte antigen (HLA)-DR+ CD8+ T cells suggesting that both B cells and CD8+ T cells were preferentially recruited to and activated within the CSF- (and putatively central nervous system (CNS)-) compartment.ConclusionWe confirm the association of CASPR-2 serum antibodies with cerebellar ataxia and provide the first evidence for a combined humoral and cellular immune response in this novel antibody-associated inflammatory CNS disease.
Highlights
Antibodies to the complex of voltage-gated K+ channels (VGKC) and associated neuronal membrane proteins (contactin-associated protein-2 (CASPR-2; axon); contactin-2; leucine-rich glioma inactivated 1 protein (LGI-1; synapse)) are detected in Recently, CASPR-2 antibodies strongly labeling axons of cerebellar granule neurons have been identified in sera from nine patients with otherwise unexplained progressive cerebellar ataxia [4]
We confirm the association of CASPR-2 serum antibodies with cerebellar ataxia and provide the first evidence for a combined humoral and cellular immune response in this novel antibody-associated inflammatory Central nervous system (CNS) disease
Antibodies to the complex of voltage-gated K+ channels (VGKC) are predominantly of the IgG4 subclass supposed to reversibly disrupt the respective protein complexes leading to altered synaptic transmission and plasticity as well as neuronal excitability and axonal conduction without overt cytotoxicity [1,10]
Summary
Antibodies to the complex of voltage-gated K+ channels (VGKC) and associated neuronal membrane proteins (contactin-associated protein-2 (CASPR-2; axon); contactin-2 (ensheathing glial cells); leucine-rich glioma inactivated 1 protein (LGI-1; synapse)) are detected in Recently, CASPR-2 antibodies strongly labeling axons of cerebellar granule neurons have been identified in sera from nine patients with otherwise unexplained progressive cerebellar ataxia [4]. In these patients, MRI was unremarkable or showed mild to severe cerebellar atrophy. We add excessive cellular CSF and peripheral blood (PB) analysis of another patient with non-paraneoplastic cerebellar ataxia with CASPR-2 antibodies
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