Cerebellar disease associated with anti-glutamic acid decarboxylase antibodies: review

Abstract

Several neurological syndromes have been recognized associated to GAD antibodies. Among those disorders, cerebellar ataxia (CA) is one of the most common, along with stiff-person syndrome. Patients with GAD associated CA present with a progressive pancerebellar syndrome, with a subacute or chronic evolution, along with other neurological manifestations such as stiffness, oculomotor dysfunction, epilepsy, and cognitive dysfunction. These symptoms may be preceded by the so-called "brainstem attacks", where manifestations consistent with transient dysfunction of the brainstem may be observed. These patients frequently have extra-neurologic autoimmune manifestations such as diabetes mellitus type 1, polyendocrine autoimmune syndrome, pernicious anemia, vitiligo, etc. A proportion of patients may present with an underlying neoplasia, but the course is less aggressive than in those patients with classical paraneoplastic CA with onconeural antibodies. The diagnosis is based on the present of high serum and CSF titers of GAD antibodies, with intrathecal production of such antibodies. Treatment is aimed to decrease the immunological response with intravenous immunoglobulin, steroids, rituximab and oral immunosuppressive drugs. A subacute presentation and rapid initiation of immunotherapy seem to be the predictors of a favorable clinical response.

Autoimmune Diseases and Psychotic Disorders

“…Diabetes mellitus type 1 is a disease characterized by the presence of glutamic acid decarboxylase (GAD) antibodies. These autoantibodies have been linked with neurological problems (47), and thus have shown ability to cross the blood brain barrier, making them an interesting topic in the discussion of pathophysiological mechanisms. However, conflicting results have been found regarding the association of type 1 diabetes and psychotic disorders.…”

Pure Red Cell Aplasia (PRCA) and Cerebellar Hypoplasia as Atypical Features of Polyglandular Autoimmune Syndrome Type I (APS-1): Two Sisters With the Same AIRE Mutation but Different Phenotypes

“…In literature there are no reported cases of APS-1 with cerebellar hypoplasia, but it is described in association with hereditary bone marrow failure like Fanconi anemia (15), dyskeratosis congenital (16), Diamond-Blackfan anemia (17), congenital amegakaryocytic thrombocytopenia (18), or ataxia-pancytopenia syndrome (19). Some cases of patients with cerebellitis and APS-1 are described (20); in these patients high serum and CSF titers of anti-GAD were found, with intrathecal production of such antibodies. In our patient serum and CSF analysis were performed after the transplantation, when the child developed an encephalitis, and they resulted negative for all autoantibodies against neuronal surface and intracellular antigens but positive for oligoclonal bands in CSF.…”

Autoimmune Vestibulocerebellar Syndromes

“…The GAD65 antibody has been one of the commonly associated and well-studied antibodies in the context of vestibulocerebellar syndromes. 83 Epidemiology: the incidence of cerebellar ataxia from GAD65 antibody syndrome is estimated to be approximately 1 to 2 cases per million. 84 GAD65 antibody related cerebellar ataxia accounts for 1.9% of patients with sporadic ataxia 85 and 35% of autoimmune cerebellar ataxia.…”