Stiff-person syndromes - Motor cortex hyperexcitability correlates with anti-GAD autoimmunity

Objectives: To investigate whether motor cortex excitability is enhanced in both stiff-person syndrome (SPS) and its "plus" variant, progressive encephalomyelitis with rigidity ( PER), and related to autoimmunity against glutamic acid decarboxylase ( GAD). Methods: The authors compared 21 patients with SPS or PER ( 7 untreated, 14 treated) with 14 age-matched healthy controls and used transcranial magnetic stimulation (TMS, paired-pulse paradigm) to investigate intracortical inhibition (ICI) and intracortical facilitation (ICF). GAD autoantibody levels in serum and CSF were determined by radioimmunoassay. Results: The authors found significantly enhanced motor cortex excitability in untreated SPS and PER patients. GABAmimetic medication significantly reduced ICF but did not affect ICI. Motor cortex excitability was more enhanced in patients with GAD antibodies than in patients without GAD antibodies and correlated positively with GAD antibody levels in CSF. Conclusions: The motor cortex is hyperexcitable in SPS and PER patients. However, hyperexcitability is partly masked by GABAmimetic treatment. Correlation of elevated GAD antibody levels with enhanced ICF suggests that motor cortex hyperexcitability in SPS and PER is related to anti-GAD autoimmunity.