Cerebellar Ataxia With Anti–Glutamic Acid Decarboxylase Antibodies

Abstract

These results suggest a link between high level of GAD-Ab and some cases of cerebellar ataxia, particularly women with IDDM. If high serum levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluated for the presence of oligoclonal IgG bands and intrathecal synthesis of GAD-Ab to further prove an autoimmune origin of the syndrome.

Type 1 Diabetes Mellitus and Drug-resistant Epilepsy: Presence of High Titer of Anti-Glutamic Acid Decarboxylase Autoantibodies in Serum and Cerebrospinal Fluid

“…Interestingly, few of these patients had a history or any clinical signs of autoimmune disease: one patient had a history of hypothyroidism and oligomenorrohea and none had any history or sign of type 1 diabetes (15). Their features appear to be quite different from those of other neurological disorders associated with anti-GAD antibodies, such as SPS, cerebellar ataxia, and palatal myoclonus, in which patients are frequently affected with type 1 diabetes and/or other autoimmune diseases (7,(9)(10)(11)(12)(13). However, the present case had subclinical hypothyroidism due to Hashimoto's disease.…”

Clinical characteristics of patients with cerebellar ataxia associated with anti-GAD antibodies

“…The precise mechanism behind this condition remains unknown 5,6,8,12 . The disease affects mostly women in their sixth decade of life 5,6,8,12 . The present study evaluated three patients in their fifth and sixth decades of life, with two of these patients being male.…”

“…The exact pathogenic role of GAD-ab in the cerebellar ataxias has yet to be fully understood; however, experimental data have suggested a direct excitotoxic effect of GAD-ab on Purkinje cells 8 . The presence of GAD-ab serves to confirm a possible autoimmune pathogenesis in the syndrome of cerebellar ataxia 5,6,8 . The objective of the current investigation was to evaluate a series of patients with cerebellar ataxia associated to anti-GAD-ab, comparing their clinical characteristics and outcomes.…”

“…The cerebellum is an encephalic region highly susceptible to immune-mediated mechanisms. Cerebellar ataxia associated with anti-GAD-ab (CA-GAD-ab) is a rare and potentially treatable form of immune-mediated cerebellar ataxia, the detection of which is increasing 5,6,7 . The exact pathogenic role of GAD-ab in the cerebellar ataxias has yet to be fully understood; however, experimental data have suggested a direct excitotoxic effect of GAD-ab on Purkinje cells 8 .…”

Pathogenicity of autoantibodies in neurological disorders

“…A high titre is thought to distinguish GADAbs in SPS from GADAbs infrequently reported in other neurological diseases-thymoma (5%) and normal healthy controls (1%) 10 . Although high titres of GADAb in the range seen in SPS have been reported in some cases of autoimmune polyglandular syndrome, idiopathic late-onset cerebellar ataxia and drugresistant localisation-related epilepsy 11,12 , the prevalence of GADAbs in these diseases are rare. However, GADAbs are detected in up to 80% of patients with T1DM where it is both a marker of disease and predictor of risk 13 , but the titre is considered to be much lower than that of SPS 11 , although differences in reactivity with GAD epitopes has also been suggested.…”