Changes of cortical excitability after dopaminergic treatment in restless legs syndrome

Abstract 

Objective

Dopaminergic pathways are most likely involved in the pathophysiology of restless legs syndrome (RLS). In previous investigations, an alteration of cortical excitability was suggested to be related to a dopaminergic dysfunction in RLS. The purpose of our study was to compare practice-dependent plasticity in RLS patients before and after a month of dopaminergic treatment.

Methods

Single-pulse transcranial magnetic stimulation (TMS) was used to define motor evoked potential (MEP) amplitude, motor threshold, and silent period (SP) as well. Subjects performed three exercise blocks (bimanual motor task). MEP amplitude, registered immediately after each exercise block and after a rest period, was compared to baseline. The time course of intra-cortical inhibition was tested using paired-pulse TMS at short inter-stimulus intervals. For the single-pulse TMS procedures, we enrolled 12 patients affected by primary RLS and 12 normal subjects. For the paired-pulse TMS procedures, only six patients underwent the examination. RLS patients underwent the examination in both pre- and post-dopaminergic treatment conditions.

Results

In RLS patients MEP amplitude increased after the rest period only in the post-treatment condition, showing a delayed facilitation. After exercise, MEP amplitude increased, but not enough to be significant, showing a positive trend but not a clear-cut post-exercise facilitation. In the pre-treatment condition instead, MEP amplitude did not change either after rest period or after exercise.

RLS patients showed a marked increase of the central motor inhibition, assessed by using paired-pulse TMS at short inter-stimulus intervals after pramipexole treatment. On the contrary, the duration of the SP did not change compared to the pre-treatment condition.

Conclusions

In RLS patients after dopaminergic treatment, the main finding was the changing of MEP amplitude after rest following a motor task. Since dopaminergic treatment can reverse delayed facilitation in RLS, we hypothesized that cortical plasticity related to dopaminergic systems may play a crucial role in RLS pathophysiology.

Keywords: Restless legs syndrome, Transcranial magnetic stimulation, Cortical plasticity, Cortical excitability, Delayed facilitation, Sleep, Dopamine, Movement disorders