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

Abstract

The enzyme glutamic acid decarboxylase (GAD), present in GABAergic neurons and in pancreatic beta cells, catalyzes the conversion of gamma-aminobutyric acid (GABA). The cerebellum is highly susceptible to immune-mediated mechanisms, with the potentially treatable autoimmune cerebellar ataxia associated with the GAD antibody (CA-GAD-ab) being a rare, albeit increasingly detected condition. Few cases of CA-GAD-ab have been described. Methods This retrospective and descriptive study evaluated the clinical characteristics and outcomes of patients with CA-GAD-ab. Result Three patients with cerebellar ataxia, high GAD-ab titers and autoimmune endocrine disease were identified. Patients 1 and 2 had classic stiff person syndrome and insidious-onset cerebellar ataxia, while Patient 3 had pure cerebellar ataxia with subacute onset. Patients received intravenous immunoglobulin therapy with no response in Patients 1 and 3 and partial recovery in Patient 2. Conclusion CA-GAD-ab is rare and its clinical presentation may hamper diagnosis. Clinicians should be able to recognize this potentially treatable autoimmune cerebellar ataxia.

Neurological Syndromes Associated with Anti-GAD Antibodies

“…Brain MRI reveals an atrophy of the cerebellum, and especially of the vermis, in 43% to 57% of patients [18,81,111,112]. Similar to other immune-mediated CA, cerebellar atrophy is not present at disease onset but usually develops over time, becoming frequent and, possibly, severe in patients with a long-standing symptom evolution [81,87,112]. Positron emission tomography (PET) studies performed in patients with cerebellar atrophy show a correspondent cerebellar hypometabolism [113] confirming neuronal degeneration.…”

Consensus Paper: Latent Autoimmune Cerebellar Ataxia (LACA)

“…These patients should be evaluated carefully as they may initially show relatively minor signs of ataxia, such as difficulties with tandem gait or mild dysmetria. Such relatively subtle cerebellar manifestations may progress with time, leading to overt CA [ 68 ].…”

Cerebellar ataxia associated with anti-glutamic acid decarboxylase (anti-GAD) autoantibodies: a rare and puzzling disease

“…11 In this issue of Arquivos de Neuro-Psiquiatria, Aguiar et al 12 describe the clinical characteristics of patients with GAD Abs-CA. In their retrospective study they evaluate three patients with this condition (one female and two males, mean age 49.3 years), two of whom also had SPS.…”

“…All the patients had high GAD-Ab titers (> 100 IU/mL) without any paraneoplastic neurological syndromes. After treatment with intravenous immunoglobulin, one patient made a partial recovery but the two others showed no improvement.12 Associated endocrine disease included latent autoimmune diabetes in adults (LADA) in two patients, and autoimmune polyglandular endocrinopathy type 2, or Schmidt' s syndrome in one patient 12 . In 2016, Mitoma et al 10 published a review of guidelines for treatment of immune-mediated cerebellar ataxias.…”