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Objective : To assess the prevalence of pain in adults with spasticity and to assess the association between the subjective experience of pain and spasticity. Design: Cross-sectional study. Setting: outpatient spasticity management clinic of a rehabilitation centre. Patients: Patients with upper motor neuron lesions and spasticity (n=131) were recruited. Methods: We assessed pain intensity and location, relationship between spasticity and pain perception, and perception of pain relief from botulinum toxin type-A (BoNTA) injections. Main outcome measures: Pain perception rated on a 10-point numerical rating scale and pain quality. Results: 65% of the patients with spasticity reported presence of pain and 60% described it as an aching pain. More patients reported pain with movement (34%) compared to rest (21%). There was a statistically poor correlation between the severity of pain and spasticity (r=0.16; p>0.05). Most patients (80%) believed that their pain was related to spasticity and 62% reported that BoNTA injections decreased their pain. Conclusions: The high incidence of pain noted within our sample suggests that physicians may have to consider pain management as part of spasticity treatment. Participants reported that their pain was related to their spasticity, and that it decreased after BoNTA treatment. Further study is needed to explore the relationships between objective measures of spasticity and pain. Relation entre la toxine botulique, la spasticité et la douleur : une enquête sur la perception des patients. Objectif : Le but de l’étude était de déterminer la prévalence de la douleur chez des adultes souffrant de spasticité et d’étudier l’association entre l’expérience subjective de la douleur et la spasticité. Devis de l’étude : Il s’agit d’une étude transversale. Contexte : Cette étude a été réalisée auprès de patients fréquentant une clinique dédiée au traitement de la spasticité dans un centre de réadaptation. Patients : Des patients atteints de lésions du neurone moteur supérieur et de spasticité ont été recrutés (n=131). Méthode : Nous avons évalué l’intensité et la localisation de la douleur, la relation entre la spasticité et la perception de la douleur ainsi que la perception du soulagement de la douleur suite à des injections de toxine botulique de type A (BoNTA). Principaux critères d’évaluation : Les critères utilisés étaient la perception de la douleur évaluée sur une échelle numérique de 10 points et la qualité de la douleur. Résultats : Soixante-cinq pour cent des patients présentant de la spasticité ont rapporté la présence de douleur et 60% l’ont décrite comme une douleur sourde. Plus de patients ont rapporté de la douleur au mouvement (34%) qu’au repos (21%). La corrélation entre la sévérité de la douleur et la spasticité était faible au point de vue statistique (r=0,16 ; p>0,05). La plupart des patients (80%) croyaient que leur douleur était reliée à la spasticité et 62% rapportaient que les injections de BoNTA diminuaient la douleur. Conclusions : L’incidence élevée de douleur notée dans notre échantillon de patients suggère que les médecins devraient considérer la gestion de la douleur comme faisant partie du traitement de la spasticité. Les participants ont rapporté que leur douleur était reliée à la spasticité et qu’elle diminuait après le traitement par la BoNTA. Des études supplémentaires seront nécessaire afin d’explorer la relation entre des mesures objectives de la spasticité et la douleur.

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn–Tolosa–Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, n = 19; placebo, n = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (p= 0.003) and Week 8 (p= 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (p < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (p= 0.004) and Week 8 (p < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.

Background. Balance impairments, falls, and spasticity are common after stroke, but the effect of spasticity on balance control after stroke is not well understood. Methods. In this cross-sectional study, twenty-seven participants with stroke were divided into two groups, based on ankle plantar flexor spasticity level. Fifteen individuals with high spasticity (Modified Ashworth Scale (MAS) score of ≥2) and 12 individuals with low spasticity (MAS score <2) completed quiet standing trials with eyes open and closed conditions. Balance control measures included centre of pressure (COP) root mean square (RMS), COP velocity, and COP mean power frequency (MPF) in anterior-posterior and mediolateral (ML) directions. Trunk sway was estimated using a wearable inertial measurement unit to measure trunk angle, trunk velocity, and trunk velocity frequency amplitude in pitch and roll directions. Results. The high spasticity group demonstrated greater ML COP velocity, trunk roll velocity, trunk roll velocity frequency amplitude at 3.7 Hz, and trunk roll velocity frequency amplitude at 4.9 Hz, particularly in the eyes closed condition (spasticity by vision interaction). ML COP MPF was greater in the high spasticity group. Conclusion. Individuals with high spasticity after stroke demonstrated greater impairment of balance control in the frontal plane, which was exacerbated when vision was removed.

Although falls, balance impairment, and spasticity are common post-stroke, their interrelationship remains unclear. We review the literature for a) a relationship between spasticity and balance and b) the effect of botulinum toxin injections on balance. Electronic databases were searched based on two criteria: a) studies assessing balance in subjects with spasticity and b) studies examining the effect of botulinum toxin on balance. The primary findings were a) balance is impaired in subjects with spasticity, but only one study assessed relationship between spasticity and balance; and b) four studies reported that balance improves following botulinum treatment for limb spasticity. Persons with spasticity demonstrate impaired balance, but the correlation between spasticity and balance has not been adequately assessed in the literature. Evidence for balance changes following botulinum toxin is weak because of lack of randomization, control group comparison, objective balance assessment measures, and standard clinical scales.

Paratonia is a form of hypertonia characterized by an inability to relax muscles in the setting of cognitive impairment. Paratonia results in pain, refusal of care, and caregiver burden. We sent surveys to 67 Canadian physiatrists and neurologists regarding their experience treating paratonia with botulinum toxin A (BoNT-A). Twenty-seven survey respondents were included in the analysis. Thirteen percent of survey respondents treating paratonia with BoNT-A reported a significant clinically relevant improvement; 74% endorsed a moderately clinically relevant improvement; 13% endorsed a slight clinically relevant improvement. Ninety percent of survey respondents endorsed significant barriers in treating paratonia with BoNT-A.

Spin-related emission properties have important applications in the future information technology; however, they involve microscopic ferromagnetic coupling, antiferromagnetic or ferrimagnetic coupling between transition metal ions and excitons, or d state coupling with phonons is not well understood in these diluted magnetic semiconductors (DMS). Fe3+ doped ZnSe nanoribbons, as a DMS example, have been successfully prepared by a thermal evaporation method. Their power-dependent micro-photoluminescence (PL) spectra and temperature-dependent PL spectra of a single ZnSe:Fe nanoribbon have been obtained and demonstrated that alio-valence ion doping diminishes the exciton magnetic polaron (EMP) effect by introducing exceeded charges. The d-d transition emission peaks of Fe3+ assigned to the 4T2 (G) → 6A1 (S) transition at 553 nm and 4T1 (G) → 6A1 (S) transition at 630 nm in the ZnSe lattice have been observed. The emission lifetimes and their temperature dependences have been obtained, which reflected different spin–phonon interactions. There exists a sharp decrease of PL lifetime at about 60 K, which hints at a magnetic phase transition. These spin–spin and spin–phonon interaction related PL phenomena are applicable in the future spin-related photonic nanodevices.

Although therapeutic treatments are intended to help alleviate symptoms associated with disease, safety must be carefully considered and monitored to confirm continued positive benefit/risk balance. The objective of MOBILITY was to study the long-term safety of onabotulinumtoxinA for treatment of various therapeutic indications. A prospective, multicenter, observational, Phase IV Canadian study in patients treated with onabotulinumtoxinA for a therapeutic indication. Dosing was determined by the participating physician. Adverse events (AEs) were recorded throughout the study. Patients (n = 1372) with adult focal spasticity, blepharospasm, cerebral palsy, cervical dystonia, hemifacial spasm, hyperhidrosis, or \"other\" diagnoses were enrolled into the safety cohort. Eighty-three patients (6%) reported 209 AEs; 44 AEs in 24 patients (2%) were considered treatment-related AEs. Seventy-two serious AEs were reported by 38 patients (3%); 10 serious AEs in 5 patients (0.4%) were considered treatment related. Most commonly reported treatment-related AEs were muscular weakness (n = 7/44) and dysphagia (n = 6/44). In patients with follow-up for up to six treatments with onabotulinumtoxinA, treatment-related AEs were reported in <2% of the safety population over the course of nearly 5 years. Our findings from MOBILITY provide further evidence that onabotulinumtoxinA treatment is safe for long-term use across a variety of therapeutic indications.

Background: OnabotulinumtoxinA is an efficacious treatment option for patients with various conditions. Although studies have reported on the efficacy of onabotulinumtoxinA, quality of life (QoL) data are limited. This study evaluated QoL in patients treated with onabotulinumtoxinA across various therapeutic indications. Methods: MDs on BOTOX Utility (MOBILITY) was a prospective, multicenter, observational Canadian study in patients initiating (naïve) or receiving ongoing (maintenance) onabotulinumtoxinA treatment. Health utility was the primary outcome measure and was obtained from the Short Form-12 Health Survey using the Short Form-6D at baseline, week 4 posttreatment, and up to five subsequent treatment visits. The safety cohort included patients who received ≥1 onabotulinumtoxinA treatment. Results: The efficacy cohort included 1062 patients; the majority were Caucasian, female, and on maintenance onabotulinumtoxinA treatment. Adult focal spasticity (n=398), blepharospasm (n=81), cerebral palsy (n=22), cervical dystonia (n=234), hemifacial spasm (n=116), and hyperhidrosis (n=211) patients were included. Baseline health utility was generally higher in maintenance versus naïve patients; however, naïve patients showed the greatest improvements over time. Health utility was generally maintained or trended toward improvement across all cohorts, including maintenance patients who had been treated for up to 22 years before study entry. Eighteen of 1222 patients (2%) in the safety cohort reported 28 treatment-related adverse events; eight were serious in four patients. Conclusion: MOBILITY is the largest prospective study to date to provide QoL data over a variety of therapeutic indications following treatment with onabotulinumtoxinA. Although the QoL burden varies by disease, data suggest that long-term treatment may help improve or maintain QoL over time. Améliorations concrètes et à long terme de la qualité de vie de patients ayant bénéficié d’un traitement thérapeutique d’onabotulinumtoxinA. Contexte : L’injection d’onabotulinumtoxinA est une option thérapeutique efficace pour des patients atteints d’affections variées. Bien que des études aient signalé son efficacité, les données portant sur la qualité de vie (QV) des patients traités demeurent limitées. La présente étude vise donc à évaluer, eu égard à diverses indications thérapeutiques, la QV de patients traités au moyen de l’onabotulinumtoxinA. Méthodes : MDs on BOTOX Utility (MOBILITY) est une étude canadienne multicentrique d’observation prospective ayant été menée chez des patients qui n’avaient reçu jusque-là aucun traitement d’onabotulinumtoxinA et chez des patients qui bénéficiaient de façon continue d’un tel traitement dû à un problème chronique. L’état de santé (health utility) a été défini comme le principal indicateur de résultat. Il a été déterminé à partir du SF-12 (Short Form-12 Health Survey) en utilisant comme référence le SF-6D (4 semaines de suivi post-traitement et jusqu’à cinq visites de suivi). La cohorte évaluant la tolérance incluait des patients qui avaient reçu ≥1 traitement d’onabotulinumtoxinA. Résultats : La cohorte évaluant l’efficacité incluait 1062 patients ; la majorité d’entre eux étaient Blancs, de sexe féminin et bénéficiaient d’un traitement continu d’onabotulinumtoxinA. Des cas de spasticité focale de l’adulte (n = 398), de blépharospasme (n = 81), d’infirmité cérébrale motrice (n = 22), de dystonie cervicale (n = 234), de spasme hémifacial (n = 116) et d’hyperhidrose (n = 211) étaient inclus dans l’étude. L’état de santé général des patients traités pour un problème chronique était généralement meilleur que celui des patients qui n’avaient reçu aucun traitement. Toutefois, c’est chez ces derniers qu’on a observé les plus grandes améliorations au fil du temps. L’état de santé des patients s’est généralement maintenu ou a eu tendance à s’améliorer dans toutes les cohortes, y compris ceux qui, avant d’être inclus dans l’étude, avaient été traités pour un problème chronique pendant une période allant jusqu’à 22 ans. Sur les 1222 patients de la cohorte évaluant la tolérance, 18 d’entre eux (2 %) ont signalé un total de 28 effets indésirables liés au traitement ; 8 de ces effets se sont révélés graves dans le cas de quatre patients. Conclusions : À ce jour, MOBILITY, étude fournissant des donnés de QV en ce qui regarde diverses indications thérapeutiques à la suite d’un traitement d’onabotulinumtoxinA, demeure la plus importante étude prospective jamais réalisée. Bien que l’impact en termes de QV varie d’un état pathologique à l’autre, les données suggèrent qu’un traitement à long terme pourrait au fil du temps améliorer ou stabiliser la QV des patients.

Objective: The adverse events (AEs) with botulinum toxin type-A (BoNTA), used for indications other than spasticity, are widely reported in the literature. However, the site, dose, and frequency of injections are different for spasticity when compared to the treatment for other conditions and hence the AEs may be different as well. The objective of this study was to summarize the AEs reported in Canada and systematically review the AEs with intramuscular botulinum toxin injections to treat focal spasticity. Methods : Data were gathered from Health Canada (2009-2013) and major electronic databases. Results : In a 4 year period, 285 AEs were reported. OnabotulinumtoxinA (n=272 events): 68% females, 53% serious, 18% hospitalization, and 8% fatalities. The type of AEs reported were – muscle weakness (19%), oropharyngeal (14%), respiratory (14%), eye related (8%), bowel/bladder related (8%), and infection (5%). IncobotulinumtoxinA (n=13): 38% females, 62% serious, and 54% hospitalization. The type of AEs reported were – muscle weakness (15%), oropharyngeal (15%), respiratory (38%), eye related (23%), bowel/bladder related (15%), and infection (15%). Commonly reported AEs in the literature were muscle weakness, pain, oropharyngeal, bowel/bladder, blood circulation, neurological, gait, and respiratory problems. Conclusion: While BoNTA is useful in managing spasticity, future studies need to investigate the factors that can minimize AEs. A better understanding of the underlying mechanisms of the AEs can also improve guidelines for BoNTA administration and enhance outcomes. Réactions indésirables à des injections intramusculaires de toxine botulique utilisée pour traiter la spasticité. Objectif: Les réactions indésirables (RI) à la toxine botulique de type A (BoNTA) utilisée à des fins autres que le traitement de la spasticité ont été abondamment rapportées dans la littérature. Cependant, le point d’injection, la dose et la fréquence des injections sont différents quand elle est utilisée pour traiter la spasticité par rapport à son utilisation pour traiter d’autres affections et donc les RI peuvent également être différentes. Le but de cette étude était de présenter un sommaire des RI rapportées au Canada et de revoir systématiquement les RI rencontrées lors d’injections intramusculaires de toxine botulique pour traiter la spasticité focale. Méthode: Nous avons recueilli les données de Santé Canada de 2009 à 2013 et ainsi que celles des principales bases de données électroniques. Résultats: Au cours d’une période de 4 ans, 285 RI ont été rapportées, dont 272 RI avec l’onabotulinum toxine A. Soixante-huit pour cent sont survenues chez des femmes, 53% étaient des RI sérieuses, 18% ont nécessité une hospitalisation et 8% ont été fatales. Les RI rapportées étaient de la faiblesse musculaire (19%), des RI oropharyngées (14%), respiratoires (14%), oculaires (8%), en lien à l’intestin / la vessie (8%) et infectieuses (5%). Avec l’incobotulinum toxine A (n=13) les RI rapportées sont survenues chez des femmes dans 38% des cas, 62% étaient sérieuses et 54% ont nécessité une hospitalisation. Ces RI étaient de la faiblesse musculaire (15%), des troubles oropharyngés (15%), respiratoires (38%), en lien avec les yeux (23%), en lien avec l’intestin / la vessie (15%) et infectieuses (15%). Les RI fréquemment rapportées dans la littérature étaient la faiblesse musculaire, la douleur, des troubles oropharyngés, intestinaux / vésicaux, circulatoires, neurologiques, des troubles de la démarche et des troubles respiratoires. Conclusion: Bien que la BoNTA soit utile dans le traitement de la spasticité, des études méritent d’être entreprises pour identifier les facteurs qui pourraient minimiser les RI. Une meilleure compréhension des mécanismes sous-jacents est également susceptible d’améliorer les lignes directrices concernant l’administration de la BoNTA ainsi que les résultats de ce traitement.