Recent behavioral and imaging studies have substantially revised the classical concept of MS, increasing awareness that it is not just a disease that is limited to the myelin axonal sheath. Several findings, in fact, point to a parallel involvement of other neuronal components of the central nervous system (CNS) in MS.
Objectives: In the present study, we explored characteristics of central motor pathways related to neuronal excitability changes measured using transcranial magnetic stimulation (TMS) in individuals with MS.
Methods: 20 individuals affected with relapsing-remitting (RR) MS and 10 healthy controls were examined using TMS in order to assess intracortical excitability in the hand area of the motor cortex. All participants with MS were in disease remission. Two paired TMS pulses were delivered; the first at an intensity to generate 1mv motor evoked potential. The second pulse was delivered at 90% of active motor threshold (200µv muscle response during 20% muscle contraction). The interval between the two pulses was either 2ms to assess intracortical inhibition or 12ms to test intracortical facilitation. Analyzed parameters were: motor evoked potential (MEP) size and the area under the curve (AUC) of the MEPs.
Significant differences were noted in MEP size at both 2 and 12 ms intervals. Participants with MS showed smaller MEP sizes expressed as a percentage of unconditioned MEP size (68% versus 86%, p<0.001) at the 2ms interstimulus interval and larger MEP sizes (136% versus 117%, p<0.001) at the 12ms interstimulus interval. Comparing the AUC for the muscle response confirmed these results (2 ms: 69% versus 87% of unconditioned stimuli, p<0.001; and at 12 ms: 144% versus 120%, p<0.001).
The present findings revealed that both inhibitory and facilitatory intracortical circuits are altered in RR-MS patients. These changes may be attributed to glutamate-mediated excitatory postsynaptic enhancement in MS. Additionally, our data suggest that TMS based measures may be useful in evaluating cortical neurophysiology in individuals with MS.