Altered motor plasticity in an acute relapse of multiple sclerosis

Abstract

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 12 weeks afterwards. Motor plasticity was examined in 19 patients with clinically isolated syndrome or RRMS during a steroid-treated relapse (t1) and 12 weeks 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.

Interleukin-1β Alters Hebbian Synaptic Plasticity in Multiple Sclerosis

“…Related to this issue, another important feature to address is the contribution of different disease phases in synaptic alterations in MS. In this study, we did not find a significant difference in PAS response between relapsing and remitting patients; however, the presence of radiological activity has been previously associated with synaptic alterations [ 23 , 26 ] and may represent a possible confounding factor.…”

“…Notably, inflammation has also been associated with a paradoxical LTP-like response produced by LTD-inducing protocols both in EAE and MS [ 13 , 15 , 26 ]. IL-1β has been specifically associated with LTP induction in response to low frequency stimulation in mice hippocampal slices [ 13 ] and to LTP-like response after cTBS [ 15 ].…”

Changes in cortical motor outputs after a motor relapse of multiple sclerosis

“…Arm dexterity was assessed with the nine-hole peg test (NHPT) which is a reliable measure commonly used in neurological diseases, such as MS and stroke. 11,12 Furthermore, NHPT has been already used as measure of motor dexterity in previous studies for evaluating longitudinal changes after acute motor relapse of one side in MS. 3,13 We performed NHPT for both sides in MS subjects and controls.…”

Can Operant Conditioning of EMG-Evoked Responses Help to Target Corticospinal Plasticity for Improving Motor Function in People With Multiple Sclerosis?

“…The availability of synaptic plasticity, also known as “plasticity reserve” ( 11 ), can be measured in persons with MS by applying plasticity-inducing neuromodulation techniques, such as repetitive TMS (rTMS) at high (e.g., 20 Hz) or low (e.g., 1 Hz) frequency, rTMS with intermittent or continuous theta burst stimulation patterns (iTBS and cTBS) ( 11 , 13 , 14 , 41 , 42 ), paired associative stimulation (PAS) with TMS, and peripheral nerve stimulation (PNS) ( 12 , 23 , 43 , 44 ). They can be used to assess long-term potentiation (with high-frequency rTMS and iTBS), long-term depression (with low-frequency rTMS and cTBS), and spike-timing-dependent Hebbian-type plasticity (with PAS) ( 11 , 13 , 42 ).…”

“…Clearly, more studies are needed to determine the applicability of operant conditioning approach in people with MS, and an investigation needs to include persons with all MS subtypes. Long-term follow-up should also be part of such investigations, although often unpredictable disease progress may mask or reduce the induction of plasticity and function improvements temporally or permanently ( 23 , 44 , 49 , 74 ). Over 3.5 years of follow-up with a woman with secondary progressive MS supports a possibility of long-term maintenance of corticospinal transmission and function improvements with MEP operant conditioning ( 104 ).…”