Evidence by functional imaging studies suggests the role of left dorsolateral prefrontal cortex (DLPFC) in the inhibitory control of nociceptive transmission system. Repetitive transcranial magnetic stimulation (rTMS) is able to modulate pain response to capsaicin. In the present study, we evaluated the effect of DLPFC activation (through rTMS) on nociceptive control in a model of capsaicin-induced pain. The study was performed on healthy subjects that underwent capsaicin application on right or left hand. Subjects judged the pain induced by capsaicin through a 0–100 VAS scale before and after 5 Hz rTMS over left and right DLPFC at 10 or 20 min after capsaicin application in two separate groups (8 subjects each). Left DLPFC-rTMS delivered either at 10 and 20 min after capsaicin application significantly decreased spontaneous pain in both hands. Right DLPFC rTMS showed no significant effect on pain measures. According to these results, stimulation of left DLPFC seems able to exert a bilateral control on pain system, supporting the critical antinociceptive role of such area. This could open new perspectives to non-invasive brain stimulation protocols of alternative target area for pain treatment.

Recent evidence suggests a role for cerebellum in pathophysiology of dystonia. Here we explored, the cerebellar modulation of motor cortex in patients with focal upper limb dystonia. Eight patients and eight controls underwent a transcranial magnetic stimulation protocol to study the cerebellar-brain-inhibition (CBI): a conditioning cerebellar stimulus (CCS) was followed 5 ms after by the contralateral motor cortex stimulation (test stimulus: TS). We explored the effects of CBI on MEP amplitude, short intracortical inhibition (SICI) and intracortical facilitation (ICF) measures. At baseline no differences in TS-MEP amplitude, SICI or ICF were found between patients and controls. Cerebellar-conditioning significantly reduced TS-MEP amplitude, increased ICF, and decreased SICI in control subjects. In contrast, no changes in these neurophysiological measures were observed in the motor cortex of patients, regardless of which side was tested. If further confirmed, these findings suggest a reduced cerebellar modulation of motor cortex excitability in patients with focal dystonia.

ObjectiveTo compare the clinical features of patients showing a classical phenotype of facioscapulohumeral muscular dystrophy (FSHD) with genetic and epigenetic characteristics of the FSHD1 and FSHD2 loci D4Z4 and SMCHD1.MethodsThis is a national multicenter cohort study. We measured motor strength, motor function, and disease severity by manual muscle testing sumscore, Brooke and Vignos scores, clinical severity score (CSS), and age-corrected CSS, respectively. We correlated these scores with genetic (D4Z4 repeat size and haplotype; SMCHD1 variant status) and epigenetic (D4Z4 methylation) parameters.ResultsWe included 103 patients: 54 men and 49 women. Among them, we identified 64 patients with FSHD1 and 20 patients with FSHD2. Seven patients had genetic and epigenetic characteristics of FSHD1 and FSHD2, all carrying repeats of 9–10 D4Z4 repeat units (RU) and a pathogenic SMCHD1 variant. In the remaining patients, FSHD was genetically excluded or remained unconfirmed. All clinically affected SMCHD1 mutation carriers had a D4Z4 repeat of 9–16 RU on a disease permissive 4qA haplotype. These patients are significantly more severely affected by all clinical scales when compared to patients with FSHD1 with upper-sized FSHD1 alleles (8–10 RU).ConclusionThe overlap between FSHD1 and FSHD2 patients in the 9–10 D4Z4 RU range suggests that FSHD1 and FSHD2 form a disease continuum. The previously established repeat size threshold for FSHD1 (1–10 RU) and FSHD2 (11–20 RU) needs to be reconsidered.Clinicaltrials.gov identifierNCT01970735.