title: Spontaneous downbeat nystagmus as a clue for the diagnosis of ataxia associated with anti-GAD antibodies.
abstract: Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the conversion of glutamic acid to the neurotransmitter gamma-amino butyric acid. Antibodies against GAD (anti-GAD-Ab) are associated with an array of autoimmune-related neurological conditions, such as stiff-person syndrome, cerebellar ataxia, epilepsy and limbic encephalitis. The clinical spectrum of ataxia associated with anti-GAD-Ab comprises slowly progressive cerebellar ataxia syndrome evolving in months or years, associated with cerebellar atrophy on brain MRI. There are few reports of patients with ataxia associated with anti-GAD-Ab presenting with abnormal ocular movements, such as downbeat nystagmus (DBN).We present two patients with ataxia associated with anti-GAD-Ab from a large series of ataxic subjects who presented with cerebellar ataxia combined with spontaneous DBN. All patients underwent a thorough neurological evaluation with the use of ataxia scales, brain MRI scans, cerebrospinal fluid examination, 18FDG-PET/CT scans, laboratory work-up with on coneural and immune encephalitis antibodies, serum and cerebrospinal fluid levels of anti-GAD-Ab, and the antibody specificity index to measure the intrathecal synthesis of anti-GAD-Ab. All patients were treated with cycles of intravenous immunoglobulin and had mild/partial ataxia improvement and no improvement of DBN. The finding of DBN may work as a diagnostic clue in the context of adult-onset non-hereditary ataxias.
authors.affiliation: Movement Disorders Unit, Neurology Service, University Hospital, Department of Internal Medicine, Faculty of Medicine, Federal University of Juiz de Fora (UFJF), Juiz de Fora, MG, Brazil.
authors.forename: Thiago Cardoso
authors.initials: TC
authors.lastname: Vale
authors.affiliation: Division of General Neurology and Ataxia Unit, Department of Neurology, Universidade Federal São Paulo, SP, Brazil. Electronic address: jlpedroso.neuro@gmail.com.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Pedroso
authors.affiliation: Department of Neurology, Faculdade de Medicina do ABC, Santo André, SP, Brazil.
authors.forename: Rafaela Almeida
authors.initials: RA
authors.lastname: Alquéres
authors.affiliation: Division of General Neurology and Ataxia Unit, Department of Neurology, Universidade Federal São Paulo, SP, Brazil.
authors.forename: Lívia Almeida
authors.initials: LA
authors.lastname: Dutra
authors.affiliation: Division of General Neurology and Ataxia Unit, Department of Neurology, Universidade Federal São Paulo, SP, Brazil.
authors.forename: Orlando Graziani Povoas
authors.initials: OG
authors.lastname: Barsottini
mesh_terms: D000368:Aged; D001259:Ataxia / Q000175:diagnosis* / Q000503:physiopathology*; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009759:Nystagmus, Pathologic / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D019788:Fluorodeoxyglucose F18; D005968:Glutamate Decarboxylase
keywords: Anti-GAD; Ataxia; Cerebellar ataxia; Immune-mediated ataxia