Neurological Syndromes Associated with Anti-GAD Antibodies

Abstract

Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter within the central nervous system. GAD antibodies (Ab) have been associated with multiple neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and limbic encephalitis, which are all considered to result from reduced GABAergic transmission. The pathogenic role of GAD Ab is still debated, and some evidence suggests that GAD autoimmunity might primarily be cell-mediated. Diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid. Due to the relative rarity of these syndromes, treatment schemes and predictors of response are poorly defined, highlighting the unmet need for multicentric prospective trials in this population. Here, we reviewed the main clinical characteristics of neurological syndromes associated with GAD Ab, focusing on pathophysiologic mechanisms.

Anti-GAD associated post-infectious cerebellitis after COVID-19 infection

“…The dramatic response to immune therapies such as high-dose steroids and intravenous immunoglobulin also suggests the existence of an underlying autoimmune process. Besides, anti-GAD-associated neurological disorders are frequently accompanied by autoimmune disorders such as autoimmune thyroiditis and gluten sensitivity, as in our case [26]. Various side effects are reported with high-dose favipiravir in the treatment of COVID-19 [27].…”

Treatment of Anti-GAD65 Autoimmune Encephalitis With Methylprednisolone

“…Anti-GAD65 antibodies have been reported in association with stiff-person syndrome, limbic encephalitis, and refractory epilepsy. 11 , 24 These antibodies have been demonstrated to bind presynaptic terminals of GABAergic interneurons, leading to neurologic and cerebellar dysfunction. 25 A case report published in 2009 reported that anti-GAD65 antibodies were found in the CSF of a 16-year-old female with new onset seizures and confusion.…”

“…9,10 Antibodies against GAD have been implicated in a number of neurologic disorders, including seizures, cerebellar ataxia, stiff-person syndrome, epilepsy, and encephalitis. 11 Anti-GAD antibodies have 2 major isoforms: GAD65 and GAD67, with the former being highly prevalent within axon terminals and synaptic vesicles. 9 Anti-GAD antibodies are a rare cause of autoimmune encephalitis that lacks symptom specificity, often leading to a failure in diagnosing or mischaracterizing the underlying etiology.…”

“… 9 , 10 Antibodies against GAD have been implicated in a number of neurologic disorders, including seizures, cerebellar ataxia, stiff-person syndrome, epilepsy, and encephalitis. 11 Anti-GAD antibodies have 2 major isoforms: GAD65 and GAD67, with the former being highly prevalent within axon terminals and synaptic vesicles. 9 …”

Glutamic Acid Decarboxylase (GAD-65) Autoimmunity Associated With Profound Daytime Hypersomnia, Nighttime Insomnia, Mild Autonomic Neuropathy and Axonal Sensori-Motor Polyneuropathy: A Case Report on a New Phenotype

“…GAD-65 antibody is a beta-cell pancreatic islet antibody and a serological marker for susceptibility to type I diabetes, thyroid diseases (Grave's disease, Hashimoto's thyroiditis), pernicious anemia, Addison's disease, and vitiligo. Low titer antibodies to GAD-65 are found in eight percent of healthy subjects older than age 50 [1].…”