Clinico-pathological findings in a patient with progressive cerebellar ataxia, autoimmune polyendocrine syndrome, hepatocellular carcinoma and anti-GAD autoantibodies

Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias

“…In agreement with this assumption, cerebellar atrophy is evident with the progression of the disease [2]. The autopsy report in a patient with advanced stage CA indicated complete loss of PCs [57, 58]. Thus, GAD65Ab-induced decrease in GABA release characteristically elicits chained and cascaded effects in the cerebellum.…”

“…Although this imbalance is assumed to elicit excitotoxicity in cerebellar neurons, detailed mechanisms underlying prominent loss of cerebellar neurons [57, 58] have not been elucidated. In the following section, we will review diverse glutamate-associated mechanisms leading to cell death (see Figure 4).…”

Cerebellar Ataxia and Glutamic Acid Decarboxylase Antibodies

“…Previous autopsy studies 15,16 of patients with CA and GAD65-Abs revealed selective loss of Purkinje cells. However, the clinical improvement observed in some of our patients indicates that part of the cerebellar dysfunction at the time of diagnosis may be due to functional impairment that can be reversed by early onset of immunotherapy.…”

Prevalence and immunological spectrum of temporal lobe epilepsy with glutamic acid decarboxylase antibodies

“…In addition, a protein of the Coxsackie virus has been implicated as an environmental trigger of DM1 [18]. Moreover, transient expression of GAD-ab has been reported in some patients with diabetes after an acute pancreatitis [19] or fulminant diabetes mellitus onset [20] and in a patient with cerebellar ataxia + pharmacoresistant epilepsy in whom GAD-ab disappeared after a period of immunosuppressive treatment (corticosteroids + azathioprine) [21] but, to our knowledge, our patient is the first reported with high GAD-ab, CNS involvement and spontaneous remission.…”