Background: Patients with stiff-person syndrome (SPS) have circulating antibodies against glutamic acid decarboxylase, the rate-limiting enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). Although the patients' symptoms of stiffness and unexpected spasms can be explained on the basis of reduced or impaired inhibitory neurotransmitters, such as GABA, it is unclear whether the level of GABA in the brains of these patients is reduced and, if so, whether the reduction is due to anti-glutamic acid decarboxylase antibodies.
Objective: To measure GABA levels in the brains of patients with SPS.
Design: Prospective case-control study.
Setting: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.
Patients: Eight patients with SPS with high titers of circulating anti-glutamic acid decarboxylase antibodies and typical clinical symptoms of SPS and 16 control subjects.
Main outcome measures: Results of brain magnetic resonance imaging and magnetic resonance spectroscopy, which measures GABA levels in specific brain regions.
Results: No abnormalities were noted on brain magnetic resonance images. A prominent and significant decrease in GABA level was, however, observed in the sensorimotor cortex and a smaller decrease in the posterior occipital cortex but not in the cingulate cortex or pons.
Conclusions: The reduction of brain GABA in patients with SPS supports the clinical symptoms and indicates that the inhibitory GABAergic pathways are involved in the disease. Regardless of the responsible autoantigens, in SPS autoantibodies block the function of GABAergic neurons and interfere with the synthesis of GABA but do not cause structural changes in the brain.