Neurochondrin neurological autoimmunity

Abstract

ObjectivesTo describe the neurologic spectrum and treatment outcomes for neurochondrin-IgG positive cases identified serologically in the Mayo Clinic Neuroimmunology Laboratory.MethodsArchived serum and CSF specimens previously scored positive for IgGs that stained mouse hippocampal tissue in a nonuniform synaptic pattern by immunofluorescence assay (89 among 616,025 screened, 1993–2019) were reevaluated. Antibody characterization experiments revealed specificity for neurochondrin, confirmed by recombinant protein assays.ResultsIgG in serum (9) or CSF (4) from 8 patients yielded identical neuron-restricted CNS patterns, most pronounced in hippocampus (stratum lucidum in particular), cerebellum (Purkinje cells and molecular layer), and amygdala. All were neurochondrin-IgG positive. Five were women; median symptom onset age was 43 years (range, 30–69). Of 7 with clinical data, 6 presented with rapidly progressive cerebellar ataxia, brainstem signs, or both; 1 had isolated unexplained psychosis 1 year prior. Five of 6 had cerebellar signs, 4 with additional brainstem symptoms or signs (eye movement abnormalities, 3; dysphagia, 2; nausea and vomiting, 1). One patient with brainstem signs (vocal cord paralysis and VII nerve palsy) had accompanying myelopathy (longitudinally extensive abnormality on MRI; aquaporin-4-IgG and myelin oligodendrocyte glycoprotein-IgG negative). The 7th patient had small fiber neuropathy only. Just 1 of 7 had contemporaneous cancer (uterine). Six patients with ataxia or brainstem signs received immunotherapy, but just 1 remained ambulatory. At last follow-up, 5 had MRI evidence of severe cerebellar atrophy.ConclusionIn our series, neurochondrin autoimmunity was usually accompanied by a nonparaneoplastic rapidly progressive rhombencephalitis with poor neurologic outcomes. Other phenotypes and occasional paraneoplastic causes may occur.

ANA Investigates: Pioneering Unbiased Diagnostics

“…Outside of the UCSF Center for Next‐Gen Precision Diagnostics, several other laboratories are conducting promising research in the development and utility of unbiased diagnostic testing methods. These include the Mayo Clinic Neuroimmunology Laboratory, the Laboratory for the Study of the Pathogenesis of Immune‐Mediated Neurological Disorders, and the Oxford Autoimmune Neurology Group . In addition to the UCSF Center for Next‐Gen Precision Diagnostics, these laboratories have been instrumental in identifying many of the known autoantibody‐associated syndromes using a variety of direct biochemical methods to characterize collections of large syndromically similar clinical cohorts from around the world.…”

Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia

“…CSF had an inflammatory profile in all patients, including pleocytosis, elevated protein, oligoclonal bands and/or increased IgG index. While some MRIs were initially normal or showed increased T2/FLAIR signal (mainly in pons, midbrain, and hippocampus), almost all patients eventually developed significant cerebellar atrophy on subsequent MRI scans ( 27 , 28 ). Malignancy was only identified in one patient (uterine carcinoma) ( 28 ).…”

“…While some MRIs were initially normal or showed increased T2/FLAIR signal (mainly in pons, midbrain, and hippocampus), almost all patients eventually developed significant cerebellar atrophy on subsequent MRI scans ( 27 , 28 ). Malignancy was only identified in one patient (uterine carcinoma) ( 28 ). Unfortunately, none of the patients treated with immunotherapy showed any signs of improvement.…”

Dysphagia in Neuroinflammatory Diseases of the Central Nervous System

“…Dysphagia, albeit not common, could also be seen in those with IgG autoantibody targeted against neuronal cytosolic protein, neurochondrin. These cases mostly present with cerebellar symptoms [58]. Likewise, dysphagia is described in association with anti-Ca, an established cause of cerebellar ataxia [59].…”