Clinical applications of repetitive transcranial magnetic stimulation

peer reviewedTranscranial magnetic stimulation (TMS), when delivered in trains of pulses is able to induce long-lasting changes of excitability of neuronal networks, not only in the vicinity of the stimulating coil, but also at distant sites. Results of stimulation experiments over the motor cortex indicate that the effects (excitatory or inhibitory) depend on the frequency of stimulation. These data have prompted researchers to use repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool in various brain disorders, most notably depression. However, as long as large randomized trials have not been conducted, rTMS cannot be recommended as an alternative to validated conventional therapies of such disorders

Neuropathie motrice multifocale avec blocs de conduction persistants : une entité obsolète ?

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Visually induced analgesia during face or limb stimulation in healthy and migraine subjects

Background: Visually induced analgesia (VIA) defines a phenomenon in which viewing one’s own body part during its painful stimulation decreases the perception of pain. VIA occurs during direct vision of the stimulated body part and also when seeing it reflected in a mirror. To the best of our knowledge, VIA has not been studied in the trigeminal area, where it could be relevant for the control of headache. Subjects and methods: We used heat stimuli (53°C) to induce pain in the right forehead or wrist in 11 healthy subjects (HSs) and 14 female migraine without aura (MO) patients between attacks. The subjects rated pain on a visual analog scale (VAS) and underwent contact heat-evoked potential (CHEP) recordings (five sequential blocks of four responses) with or without observation of their face/wrist in a mirror. Results: During wrist stimulation, amplitude of the first block of P1–P2 components of CHEPs decreased compared to that in the control recording when HSs were seeing their wrist reflected in the mirror (p = 0.036; Z = 2.08); however, this was not found in MO patients. In the latter, the VAS pain score increased viewing the reflected wrist (p = 0.049; Z = 1.96). Seeing their forehead reflected in the mirror induced a significant increase in N2 latency of CHEPs in HSs, as well as an amplitude reduction in the first block of P1–P2 components of CHEPs both in HSs (p = 0.007; Z = 2.69) and MO patients (p = 0.035; Z = 2.10). Visualizing the body part did not modify habituation of CHEP amplitudes over the five blocks of averaged responses, neither during wrist nor during forehead stimulation. Conclusion: This study adds to the available knowledge on VIA and demonstrates this phenomenon for painful stimuli in the trigeminal area, as long as CHEPs are used as indices of central pain processing. In migraine patients during interictal periods, VIA assessed with CHEPs is within normal limits in the face but absent at the wrist, possibly reflecting dysfunctioning of extracephalic pain control. © 2018 Sava et al

Headache Related Alterations of Visual Processing in Migraine Patients.

peer reviewedMigraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high-frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low beta). We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients. Visual evoked potentials from 20 healthy controls and 70 migraine patients (30 interictal and 20 ictal episodic migraineurs, 20 chronic migraineurs) were analyzed in the frequency domain. We compared power in the theta-alpha-low beta and gamma range between groups, and searched for correlations between the low-to-high frequency activity ratio and number of monthly headache and migraine days. Compared to healthy controls, interictal migraine patients had increased visually induced low frequency (feedback) activity. Conversely, ictal and chronic migraine patients showed an augmented gamma band (feedforward) power. The low-frequency-to-gamma (feedback/feedforward) activity ratio correlated negatively with monthly headache days and tended to do so with migraine days. Our findings show that visual processing is differentially altered depending on migraine cycle and type. Feedback control from higher order cortical areas predominates interictally in episodic migraine while migraine attacks and chronic migraine are associated with enhanced incoming afferent activity, confirming their similar electrophysiological profile. The presence of headache is associated with proportionally higher gamma (feedforward) activities. PERSPECTIVE: This study provides an insight into the pathophysiology of migraine headache from the perspective of cortical sensory processing dynamics. Patients with migraine present alterations in feedback and feedforward visual signaling that differ with the presence of headache

Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.

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Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Belgique

Purpose Electrical stimulation of the sub-thalamic nucleus (STN-DBS) is well established to alleviate motor fluctuations in advanced Parkinson’s disease but little is known about its very long-term efficacy. Methods We followed over 12 years 15 parkinsonian patients having undergone STN-DBS and compared them to a matched group of 14 patients with best medical drug therapy. All had been considered as good candidates for surgery. They were allocated to each group depending on their own decision. Results After 12 years, mortality rates were similar in both groups. In the DBS group, best “on” UPDRS III scores (on medications, on stimulation) remained significantly better and dyskinesia shorter and weaker than in the drug-treated group (on medication only). Yet, looking at independent life and quality of life (QoL) evaluated with PDQ39, no significant difference could be observed between groups at the end of follow-up, probably due to development of dopa- and stimulation-resistant motor and non-motor symptoms like falls, freezing, dementia, apathy and depression, the latter two more frequent in the DBS group. Conclusion Drug- and DBS-resistant symptoms and signs occur more often after long disease evolution and in elder patients. It might be why differences in QoL between both groups no longer existed after twelve years as, compared to other studies, our patients were older at inclusion