Altered motor plasticity in an acute relapse of multiple sclerosis

In relapsing-remitting MS (RRMS), the symptoms of a clinical relapse subside over time. Neuroplasticity is believed to play an important compensatory role. In this study, we assessed excitability-decreasing plasticity during an acute relapse of MS and 12weeks afterwards. Motor plasticity was examined in 19 patients with clinically isolated syndrome or RRMS during a steroid-treated relapse (t1) and 12weeks afterwards (t2) using paired-associative stimulation (PAS10). This method combines repetitive electric nerve stimulation with transcranial magnetic stimulation of the contralateral motor cortex to model long-term synaptic depression in the human cortex. Additionally, 19 age-matched healthy controls were assessed. Motor-evoked potentials of the abductor pollicis brevis muscle were recorded before and after intervention. Clinical disability was assessed by the multiple sclerosis functional composite and the subscore of the nine-hole peg test taken as a measure of hand function. The effect of PAS10 was significantly different between controls and patients; at t1, but not at t2, baseline-normalized postinterventional amplitudes were significantly higher in patients (106 [IQR 98-137] % post10-15 and 111 [IQR 88-133] % post20-25) compared to controls (92 [IQR 85-111] % and 90 [IQR 75-102] %). Additional exploratory analysis indicated a potentially excitability-enhancing effect of PAS10 in patients as opposed to controls. Significant clinical improvement between t1 and t2 was not correlated with PAS10 effects. Our results indicate an alteration of PAS10-induced synaptic plasticity during relapse, presumably reflecting a polarity shift due to metaplastic processes within the motor cortex. Further studies will need to elucidate the functional significance of such changes for the clinical course of MS.