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

Mapping EQ-5D utilities to GBD 2010 and GBD 2013 disability weights : results of two pilot studies in Belgium

Background: Utilities and disability weights (DWs) are metrics used for calculating Quality-Adjusted Life Years and Disability-Adjusted Life Years (DALYs), respectively. Utilities can be obtained with multi-attribute instruments such as the EuroQol 5 dimensions questionnaire (EQ-5D). In 2010 and 2013, Salomon et al. proposed a set of DWs for 220 and 183 health states, respectively. The objective of this study is to develop an approach for mapping EQ-5D utilities to existing GBD 2010 and GBD 2013 DWs, allowing to predict new GBD 2010/2013 DWs based on EQ-5D utilities. Methods: We conducted two pilot studies including respectively four and twenty-seven health states selected from the 220 DWs of the GBD 2010 study. In the first study, each participant evaluated four health conditions using the standard written EQ-5D-5 L questionnaire. In the second study, each participant evaluated four health conditions randomly selected among the twenty-seven health states using a previously developed web-based EQ-5D-5 L questionnaire. The EQ-5D responses were translated into utilities using the model developed by Cleemput et al. A loess regression allowed to map EQ-5D utilities to logit transformed DWs. Results: Overall, 81 and 393 respondents completed the first and the second survey, respectively. In the first study, a monotonic relationship between derived utilities and predicted GBD 2010/2013 DWs was observed, but not in the second study. There were some important differences in ranking of health states based on utilities versus GBD 2010/2013 DWs. The participants of the current study attributed a relatively higher severity level to musculoskeletal disorders such as ‘Amputation of both legs’ and a relatively lower severity level to non-functional disorders such as ‘Headache migraine’ compared to the participants of the GBD 2010/2013 studies. Conclusion: This study suggests the possibility to translate any utility derived from EQ-5D scores into a DW, but also highlights important caveats. We observed a satisfactory result of this methodology when utilities were derived from a population of public health students, a written questionnaire and a small number of health states in the presence of a study leader. However the results were unsatisfactory when utilities were derived from a sample of the general population, using a web-based questionnaire. We recommend to repeat the study in a larger and more diverse sample to obtain a more representative distribution of educational level and age

Motor cortex excitability changes in mild Alzheimer's disease are reversed by donepezil.

peer reviewedBACKGROUND: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). METHODS: We used transcranial magnetic stimulation to measure the active cortical motor threshold (ACMT) in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could have a direct effect on the excitability of the motor cortex. RESULTS: An increase of the ACMT was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the threshold did not differ significantly from normal subjects. CONCLUSIONS: The results suggest an early functional impairment of cholinergic neurotransmission in AD, which is associated to early changes in the excitability of the motor system

What are the impact and the optimal design of a physical prehabilitation program in patients with esophagogastric cancer awaiting surgery? : A systematic review

EP was supported by a grant from the Fonds National de la Recherche Scientifique (FRIA - FNRS). GR was supported by a grant from the Institut de Recherche Expérimentale et Clinique (Université catholique de Louvain, Brussels, Belgium). The funders had no role in the study design, collection, analysis and interpretation of data and in writing the manuscript.Peer reviewedPublisher PD

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

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

peer reviewe

In silico analysis of gene expression in V3a and the superior occipital gyrus. Relevance for migraine

Introduction: Visual manifestations are the most prominent non-painful features of migraine. During the last decades, visual area V3a has gathered attention of headache scientists because of its apparent implication on aura initiation, photophobia and cortical hyper-responsiveness related to visual motion perception. In this hypothesis-generating study, we performed an in silico analysis of gene expression in left V3a and the cerebral gyrus that harbours it (left superior occipital gyrus (lSOG)) searching for transcriptomic patterns that could be linked with migraine’s pathophysiology. Materials and methods: Neurotransmitter receptor gene expression levels in left V3a were extracted from validated brain mRNA expression models using a probabilistic volumetric mask of this region. The primary visual cortex and other sensory cortices (auditory, olfactory and somatosensory) were used as comparators. Genome-wide transcriptomic differences between the gyrus harbouring left V3a (lSOG) and the rest of the cerebral cortex were assessed using the Allen Brain Institute Human RNA micro array atlas/database. Results: Adrenergic receptor β1, dopaminergic receptor D3 and serotoninergic receptors 1B, 1F and 2A, which have been previously implicated in migraine’s pathophysiology and/or treatment, showed significantly higher expression levels on left V3a. Transcriptomic differences between the lSOG harbouring V3a and the rest of the cortex comprise genes whose products are involved in neuronal excitability (SLC17A6, KCNS1, KCNG1 and GABRQ), activation of multiple signal transduction pathways (MET) and cell metabolism (SPHKAP via its interaction with cAMP-dependent protein kinase). Conclusions: Focal gene expression analysis of V3a suggests some clues about its implication in migraine. Further studies are warranted

Welfare-Adjusted Life Years (WALY): A novel metric of animal welfare that combines the impacts of impaired welfare and abbreviated lifespan

Currently, separate measures are used to estimate the impact of animal diseases on mortality and animal welfare. This article introduces a novel metric, the Welfare-Adjusted Life Year (WALY), to estimate disease impact by combining welfare compromise and premature death components. Adapting the Disability-Adjusted Life Year approach used in human health audits, we propose WALY as the sum of a) the years lived with impaired welfare due to a particular cause and b) the years of life lost due to the premature death from the same cause. The years lived with impaired welfare are the product of the average duration of each welfare impediment, reflecting the actual condition that compromises animal welfare, the probability of an incident case developing and impaired welfare weights, representing the degree of impaired welfare. The years of life lost are calculated using the standard expected lifespan at the time of premature death. To demonstrate the concept, we estimated WALYs for 10 common canine diseases, namely mitral valve disease, dilated cardiomyopathy, chronic kidney disease, diabetes mellitus, atopic dermatitis, splenic haemangiosarcoma, appendicular osteosarcoma, cranial cruciate ligament disease, thoracolumbar intervertebral disc disease and cervical spondylomyelopathy. A survey of veterinarians (n = 61) was conducted to elicit impaired welfare weights for 35 welfare impediments. Paired comparison was the primary method to elicit weights, whereas visual analogue scale and time trade-off approaches rescaled these weights onto the desired scale, from 0 (the optimal welfare imaginable) to 1 (the worst welfare imaginable). WALYs for the 10 diseases were then estimated using the impaired welfare weights and published epidemiological data on disease impacts. Welfare impediment “amputation: one limb” and “respiratory distress” had the lowest and highest impaired welfare weights at 0.134 and 0.796, rescaled with a visual analogue scale, and 0.117 and 0.857, rescaled with time trade-off. Among the 10 diseases, thoracolumbar intervertebral disc disease and atopic dermatitis had the smallest and greatest adverse impact on dogs with WALYs at 2.83 (95% UI: 1.54–3.94) and 9.73 (95% uncertainty interval [UI]: 7.17–11.8), respectively. This study developed the WALY metric and demonstrated that it summarises welfare compromise as perceived by humans and total impact of diseases in individual animals. The WALY can potentially be used for prioritisation of disease eradication and control programs, quantification of population welfare and longitudinal surveillance of animal welfare in companion animals and may possibly be extended to production animals

Welfare-adjusted life years (WALY) : a novel metric of animal welfare that combines the impacts of impaired welfare and abbreviated lifespan

Currently, separate measures are used to estimate the impact of animal diseases on mortality and animal welfare. This article introduces a novel metric, the Welfare-Adjusted Life Year (WALY), to estimate disease impact by combining welfare compromise and premature death components. Adapting the Disability-Adjusted Life Year approach used in human health audits, we propose WALY as the sum of a) the years lived with impaired welfare due to a particular cause and b) the years of life lost due to the premature death from the same cause. The years lived with impaired welfare are the product of the average duration of each welfare impediment, reflecting the actual condition that compromises animal welfare, the probability of an incident case developing and impaired welfare weights, representing the degree of impaired welfare. The years of life lost are calculated using the standard expected lifespan at the time of premature death. To demonstrate the concept, we estimated WALYs for 10 common canine diseases, namely mitral valve disease, dilated cardiomyopathy, chronic kidney disease, diabetes mellitus, atopic dermatitis, splenic haemangiosarcoma, appendicular osteosarcoma, cranial cruciate ligament disease, thoracolumbar intervertebral disc disease and cervical spondylomyelopathy. A survey of veterinarians (n = 61) was conducted to elicit impaired welfare weights for 35 welfare impediments. Paired comparison was the primary method to elicit weights, whereas visual analogue scale and time trade-off approaches rescaled these weights onto the desired scale, from 0 (the optimal welfare imaginable) to 1 (the worst welfare imaginable). WALYs for the 10 diseases were then estimated using the impaired welfare weights and published epidemiological data on disease impacts. Welfare impediment “amputation: one limb” and “respiratory distress” had the lowest and highest impaired welfare weights at 0.134 and 0.796, rescaled with a visual analogue scale, and 0.117 and 0.857, rescaled with time trade-off. Among the 10 diseases, thoracolumbar intervertebral disc disease and atopic dermatitis had the smallest and greatest adverse impact on dogs with WALYs at 2.83 (95% UI: 1.54–3.94) and 9.73 (95% uncertainty interval [UI]: 7.17–11.8), respectively. This study developed the WALY metric and demonstrated that it summarises welfare compromise as perceived by humans and total impact of diseases in individual animals. The WALY can potentially be used for prioritisation of disease eradication and control programs, quantification of population welfare and longitudinal surveillance of animal welfare in companion animals and may possibly be extended to production animals