Motor cortex excitability in stiff-person syndrome

Muscle stiffness in stiff-person syndrome (SPS) is produced by continuous, involuntary firing of motor units that is thought to be caused by an autoim mune mediated dysfunction of GABA-ergic inhibitory neurones. We have postul ated that the loss of GABA-ergic inputs from spinal interneurones alone is insufficient to produce tonic firing of motor neurones and that excessive s upraspinal excitation could also play a role. To determine whether SPS is a ssociated with dysfunction in supraspinal GABA-ergic neurones, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in seven SPS: patients and seven age-matched healthy volunteers, SPS patients had normal central motor conduction times, normal thresholds for motor evoked potentials (MEPs) in leg muscles, and a normal MEP stimulus ve rsus response recruitment curve with increasing TMS intensities in resting hand and leg muscles. Cortical silent periods were shortened in leg muscles . Intracortical inhibition and excitation were assessed while recording fro m the abductor pollicis brevis, using a paired pulse TMS paradigm with subt hreshold conditioning stimuli, Patients had decreased inhibition and marked ly increased facilitation at short intervals. Using paired suprathreshold T MS, patients exhibited increased facilitation at 20- and 40-ms intervals. T hese results point to a hyperexcitability of the motor cortex in SPS, which could be explained by impairment of supraspinal GABA-ergic neurones, leadi ng to an impaired balance between inhibitory and excitatory intracortical c ircuitry.