Neurochondrin neurological autoimmunity

Shahar Shelly, Thomas J. Kryzer, Lars Komorowski, Ramona Miske, Mark D. Anderson, Eoin Flanagan, Shannon R. Hinson, Vanda A Lennon, Sean J Pittock, Andrew McKeon

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES: To describe the neurologic spectrum and treatment outcomes for neurochondrin-IgG positive cases identified serologically in the Mayo Clinic Neuroimmunology Laboratory. METHODS: Archived 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. RESULTS: IgG 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. CONCLUSION: In 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.

Original languageEnglish (US)
JournalNeurology(R) neuroimmunology & neuroinflammation
Volume6
Issue number6
DOIs
StatePublished - Nov 1 2019

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Autoimmunity
Immunoglobulin G
Brain Stem
Nervous System
Eye Abnormalities
Myelin-Oligodendrocyte Glycoprotein
Aquaporin 4
Vocal Cord Paralysis
Cerebellar Ataxia
Uterine Neoplasms
Spinal Cord Diseases
Purkinje Cells
Facial Nerve
Ataxia
Deglutition Disorders
Eye Movements
Amygdala
Serum
Age of Onset
Recombinant Proteins

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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Neurochondrin neurological autoimmunity. / Shelly, Shahar; Kryzer, Thomas J.; Komorowski, Lars; Miske, Ramona; Anderson, Mark D.; Flanagan, Eoin; Hinson, Shannon R.; Lennon, Vanda A; Pittock, Sean J; McKeon, Andrew.

In: Neurology(R) neuroimmunology & neuroinflammation, Vol. 6, No. 6, 01.11.2019.

Research output: Contribution to journalArticle

Shelly, Shahar ; Kryzer, Thomas J. ; Komorowski, Lars ; Miske, Ramona ; Anderson, Mark D. ; Flanagan, Eoin ; Hinson, Shannon R. ; Lennon, Vanda A ; Pittock, Sean J ; McKeon, Andrew. / Neurochondrin neurological autoimmunity. In: Neurology(R) neuroimmunology & neuroinflammation. 2019 ; Vol. 6, No. 6.
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AU - Shelly, Shahar

AU - Kryzer, Thomas J.

AU - Komorowski, Lars

AU - Miske, Ramona

AU - Anderson, Mark D.

AU - Flanagan, Eoin

AU - Hinson, Shannon R.

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AU - McKeon, Andrew

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AB - OBJECTIVES: To describe the neurologic spectrum and treatment outcomes for neurochondrin-IgG positive cases identified serologically in the Mayo Clinic Neuroimmunology Laboratory. METHODS: Archived 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. RESULTS: IgG 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. CONCLUSION: In 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.

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