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Can the early use of botulinum toxin in post stroke spasticity reduce contracture development? A randomised controlled trial.
Lindsay, C, Ispoglou, S, Helliwell, B, Hicklin, D, Sturman, S, Pandyan, A
Clinical rehabilitation. 2021;(3):399-409
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OBJECTIVE Does early treatment of spasticity with botulinum-toxin (BoNTA), in (hyper)acute stroke patients without arm-function, reduce contractures and improve function. DESIGN Randomised placebo-controlled-trial. SETTING Specialised stroke-unit. PARTICIPANTS & INTERVENTION Patients with an Action Research Arm Test (ARAT) grasp-score⩽2 who developed spasticity within six-weeks of a first stroke were randomised to receive injections of: 0.9%sodium-chloride solution (placebo) or onabotulinumtoxin-A (treatment). OUTCOME-MEASURES Spasticity, contractures, splint use and arm function (ARAT) were taken at baseline, 12-weeks post-injection and six-months after stroke. Additionally, spasticity and contractures were measured at weeks-two, four and six post-injection. RESULTS Ninety three patients were randomised. Mean time to intervention was 18-days (standard deviation = 9.3). Spasticity was lower in the treatment group with difference being significant between week-2 to 12 (elbow) and week-2 to 6 (wrist). Mean-difference (MD) varied between -8.5(95% CI -17 to 0) to -9.4(95% CI -14 to -5) µV.Contracture formation was slower in the treatment group. Passive range of motion was higher in the treatment group and was significant at week-12 (elbow MD6.6 (95% CI -0.7 to -12.6)) and week-6 (wrist MD11.8 (95% CI 3.8 to 19.8)). The use of splints was lower in the treatment group odds ratio was 7.2 (95% CI 1.5 to 34.1) and 4.2 (95% CI 1.3 to 14.0) at week-12 and month-6 respectively.Arm-function was not significantly different between the groups MD2.4 (95% CI -5.3 to 10.1) and 2.9 (95% CI -5.8 to 11.6) at week-12 and month-6 respectively. CONCLUSION BoNTA reduced spasticity and contractures after stroke and effects lasted for approximately 12-weeks. BoNTA reduced the need for concomitant contracture treatment and did not interfere with recovery of arm function. TRIAL REGISTRATION EudraCT (2010-021257-39) and ClinicalTrials.gov-Identifier: NCT01882556.
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Iron Deposits in Periaqueductal Gray Matter Are Associated with Poor Response to OnabotulinumtoxinA in Chronic Migraine.
Domínguez Vivero, C, Leira, Y, Saavedra Piñeiro, M, Rodríguez-Osorio, X, Ramos-Cabrer, P, Villalba Martín, C, Sobrino, T, Campos, F, Castillo, J, Leira, R
Toxins. 2020;(8)
Abstract
Previous studies have reported increased brain deposits of iron in patients with chronic migraine (CM). This study aims to determine the relation between iron deposits and outcome after treatment with OnabotulinumtoxinA (OnabotA). Demographic and clinical data were collected for this study through a prospective cohort study including 62 CM patients treated with OnabotA in the Hospital Clínico Universitario de Santiago de Compostela (Spain). Demographic and clinical variables were registered. Selected biomarkers in plasma during interictal periods (calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX3)) and neuroimaging changes (iron deposits in the red nucleus (RN), substantia nigra (SN), globus pallidus (GP), and periaqueductal gray matter (PAG), and white matter lesions (WML)) were determined. Subjects were classified in responders (≥50% reduction in headache days) or non-responders (<50%). Responders to treatment were younger (mean age difference = 12.2; 95% confidence interval (CI): 5.4-18.9, p = 0.001), showed higher serum levels of CGRP (≥50 ng/mL) and PTX3 (≥1000 pg/mL) and smaller iron deposits in the GP and PAG (mean difference = 805.0; 95% CI: 37.9-1572.1 μL, p = 0.040 and mean difference = 69.8; 95% CI: 31.0-108.6 μL, p = 0.008; respectively). Differences in PAG iron deposits remained significant after adjusting for age (mean difference = 65.7; 95% CI: 22.8-108.6 μL, p = 0.003) and were associated with poor response to OnabotA after adjustment for clinical and biochemical variables (odds ratio (OR) = 0.963; 95% CI: 0.927-0.997, p = 0.041). We conclude that larger PAG iron deposits are associated with poor response to OnabotA in CM.
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Effects of caffeine on neuromuscular function in a non-fatigued state and during fatiguing exercise.
Mesquita, RNO, Cronin, NJ, Kyröläinen, H, Hintikka, J, Avela, J
Experimental physiology. 2020;(4):690-706
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NEW FINDINGS What is the central question of the study? What are the effects of caffeine on neuromuscular function in a non-fatigued state and during fatiguing exercise? What is the main finding and its importance? In a non-fatigued state, caffeine decreased the duration of the silent period evoked by transcranial magnetic stimulation. Caffeine-induced reduction of inhibitory mechanisms in the central nervous system before exercise was associated with an increased performance. Individuals who benefit from caffeine ingestion may experience lower perception of effort during exercise and an accelerated recovery of M-wave amplitude postfatigue. This study elucidates the mechanisms of action of caffeine and demonstrates that inter-individual variability of its effects on neuromuscular function is a fruitful area for further work. ABSTRACT Caffeine enhances exercise performance, but its mechanisms of action remain unclear. In this study, we investigated its effects on neuromuscular function in a non-fatigued state and during fatiguing exercise. Eighteen men participated in this randomized, double-blind, placebo-controlled crossover trial. Baseline measures included plantarflexion force, drop jump, squat jump, voluntary activation of triceps surae muscle, soleus muscle contractile properties, M-wave, α-motoneuron excitability (H-reflex), corticospinal excitability, short-interval intracortical inhibition, intracortical facilitation, silent period evoked by transcranial magnetic stimulation (SP) and plasma potassium and caffeine concentrations. Immediately after baseline testing, participants ingested caffeine (6 mg·kg-1 ) or placebo. After a 1-h rest, baseline measures were repeated, followed by a fatiguing stretch-shortening cycle exercise (sets of 40 bilateral rebound jumps on a sledge apparatus) until task failure. Neuromuscular testing was carried out throughout the fatigue protocol and afterwards. Caffeine enhanced drop jump height (by 4.2%) and decreased the SP (by 12.6%) in a non-fatigued state. A caffeine-related decrease in SP and short-interval intracortical inhibition before the fatiguing activity was associated with an increased time to task failure. The participants who benefitted from an improved performance on the caffeine day reported a significantly lower sense of effort during exercise and had an accelerated postexercise recovery of M-wave amplitude. Caffeine modulates inhibitory mechanisms of the CNS, recovery of M-wave amplitude and perception of effort. This study lays the groundwork for future examinations of differences in caffeine-induced neuromuscular changes between those who are deemed to benefit from caffeine ingestion and those who are not.
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Palliative care in 9 children with neurodegeneration with brain iron accumulation.
Dangel, T, Kmieć, T, Januszaniec, A, Ważny, B
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2020;(3):653-660
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AIM: Evaluation of pediatric palliative home care of families with children suffering from neurodegeneration with brain iron accumulation (NBIA) and their parents. MATERIAL AND METHODS The children were treated at home by a multidisciplinary team. Densitometry was used to evaluate the condition of the skeletal system. Botulinum toxin was injected into the muscles in doses between 22 and 50 units/kg. The quality of palliative care was assessed on the basis of a specially designed questionnaire for parents. RESULTS The observations were performed on a group of 9 patients with NBIA. On admission, the median age of patients was 9 years (7-14). The average time of palliative home care was 1569 days (34 days-17 years). The median age at death (6 patients) was 11 years (7-15). The botulinum toxin injections gave the following results: reduction of spasticity and dystonia, reduction of spine and chest deformation, relief of pain and suffering, facilitation of rehabilitation and nursing, prevention of permanent contractures, and reduction of excessive salivation. Bone mineral density and bone strength index were reduced. Two patients experienced pathological fracture of the femur. The body mass index at admission varied between 9.8 and 14.9. In 7 cases, introduction of a ketogenic diet resulted in the increase of body mass and height. The ketogenic diet did not worsen the neurological symptoms. The parents positively evaluated the quality of care. CONCLUSION Palliative home care is the optimal form of treatment for children with NBIA.
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Vibration Versus Ice to Reduce Cosmetic Botulinum Toxin Injection Pain-A Randomized Controlled Trial.
Chorney, SR, Villwock, JA, Suryadevara, AC
Ear, nose, & throat journal. 2019;(6):351-355
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Botulinum toxin is the most commonly performed facial cosmetic procedure and pain at the injection site is a frequent patient concern. While various topical interventions have been described for analgesia, there have not been any studies comparing different techniques. We compared the use of a vibratory stimulus, ice pack application, and no intervention on injection site pain for cosmetic botulinum toxin injection. A prospective-, randomized-, individual-controlled study was conducted using a visual analog scale to assess pain. Patients received bilateral glabellar injections, with randomization into unilateral vibration, unilateral ice application, or vibration and ice on either side. We analyzed 88 injections on 22 patients. Mean visual analog scores were 26.5 (standard deviation [SD]: 23.1) among injections with vibration, 24.4 (SD: 22.9) with ice, and 29.4 (SD: 27.1) without analgesia. There was no significant difference in pain scale scores with the use of vibration, ice, or no topical anesthesia (P = .737). Further, pain scale scores did not differ significantly between medial and lateral injections nor did patients have a reduction in pain on either side of the forehead regardless of which method was used. While there may be a role for topical interventions to improve injection site analgesia, we maintain that consistently proper technique plays a greater role in improving patient tolerance. Future studies will continue to investigate the role of topical anesthesia in cosmetic facial injections and address patient-specific factors contributing to discomfort.
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Botulinum toxin injection to improve functional independence and to alleviate parenting stress in a child with advanced pantothenate kinase-associated neurodegeneration: A case report and literature review.
Lin, CI, Chen, KL, Kuan, TS, Lin, SH, Lin, WP, Lin, YC
Medicine. 2018;(20):e10709
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RATIONALE Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disease. Progressive motor symptoms such as dystonia and spasticity begin in childhood and relentlessly become incapacitating later in life. Treatments including anticholinergics and iron chelation are usually ineffective. Botulinum toxin type A (BoNT-A) is effective for adult patients with dystonia or spasticity. PATIENT CONCERNS We reported a 10-year-old female patient with advanced PKAN, manifesting as generalized dystonia and spasticity. DIAGNOSIS The patient was diagnosed with PKAN by a pediatric neurologist. INTERVENTIONS The patient received BoNT-A injection. OUTCOMES The effect was obvious at four weeks after the injection, with an improvement of 25% in Barry-Albright Dystonia Scale and 4% in Functional Independence Measure for Children score. Furthermore, there was a 3.8% reduction in Parenting Stress Index Short Form score and 8.3% improvement in Pain and Impact of Disability domain in the score of Cerebral Palsy Quality of Life for Children. LESSONS BoNT-A injection was effective to improve functional independence and to alleviate stress of caregivers in the patient with advanced PKAN.
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Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain.
Diener, SA, Breimhorst, M, Vogt, T, Krämer, HH, Drummond, PD, Geber, C, Birklein, F
European journal of pain (London, England). 2017;(8):1326-1335
Abstract
BACKGROUND The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings. METHODS Sixteen healthy subjects (8 males, mean age 27 ± 5 years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15 μg) on one thigh and electrical current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser-Doppler imaging) were assessed. (2) Four weeks later, BoNT/A (Xeomin® , 25 MU) was injected intracutaneously on both sides. (3) Seven days later, the area of BoNT/A application was determined by the iodine-starch staining and the procedure of the (1) visit was exactly repeated. In consequence of these results, 8 healthy subjects (4 males, mean age 26 ± 3 years) were included into a second set of experiments. The experimental setting was exactly the same with the exception that stimulation frequency of ES was increased to 4 Hz and BoNT/A was injected subcutaneously into the thigh, which was stimulated by capsaicin. RESULTS BoNT/A reduced the 1 Hz ES flare size (p < 0.001) and pain ratings (p < 0.01), but had no effect on 4 Hz ES and capsaicin-induced pain, hyperalgesia, or flare size, regardless of the depth of BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly increased warm detection and heat pain thresholds in naive skin (WDT, Δ 2.2 °C, p < 0.001; HPT Δ 1.8 °C, p < 0.005). CONCLUSION BoNT/A has a moderate inhibitory effect on peptidergic and thermal C-fibers in healthy human skin. SIGNIFICANCE The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.
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The effect of topical thiocolchicoside in preventing and reducing the increase of muscle tone, stiffness, and soreness: A real-life study on top-level road cyclists during stage competition.
Gervasi, M, Sisti, D, Benelli, P, Fernández-Peña, E, Calcabrini, C, Rocchi, MBL, Lanata, L, Bagnasco, M, Tonti, A, Vilberto, S, et al
Medicine. 2017;(30):e7659
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In professional road cyclists, the majority of overuse injuries affect the lower limbs and are mostly represented by contractures or muscle shortening, characterized by an increase of tone and stiffness and a variation of elasticity. Treatment and prevention of these specific conditions may include physical, supplementary, and pharmacologic support. The aim of this real-life study was to determine: first, the alterations of tone, stiffness, elasticity, and soreness of rectus femoris (RF) and biceps femoris (BF) in top class cyclists engaged in 3 multistage races, and second, whether any variable in the management of the athletes may affect the prevention and/or reduction of such alterations.Twenty-three professional cyclists competing in 3 international, cycling stage races were assessed. Athletes could receive, upon the approval of the medical staff, physical, dietary, and/or pharmacological management which could include treatments with topical over-the-counter myorelaxants to prevent and/or reduce muscle contractures. MyotonPro was used to daily measure tone, stiffness, and elasticity in RF and BF in relaxed and contracted state after every stage. In parallel, BF and RF soreness was also assessed with a Likert scale.All athletes received the same general massage management; none of them received dietary supplements; some of the athletes were treated with a topical myorelaxant thiocolchicoside (TCC 0.25%) foam 3 times daily. TCC was identified as the only variable able to affect these muscle parameters in the cyclists. Tone, stiffness (regardless of the state), and soreness significantly increased over time either in BF or RF in all athletes. In the group of athletes that used TCC (n = 11; TCC+) the increase in tone, stiffness, and soreness was significantly lower than in the group not receiving TCC (n = 12; No-TCC). Elasticity varied coherently with tone and stiffness.A very intense and protracted sport activity increases muscular tone, stiffness, and soreness over time. Topical TCC foam significantly attenuates these alterations and might represent an efficient strategy both to prevent and manage contractures and their consequences in professional cyclists as well in athletes from other disciplines involving similar workloads.
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Efficacy of two injection-site localisation techniques for botulinum toxin injections: a single-blind, crossover, randomised trial protocol among adults with hemiplegia due to stroke.
Morel, C, Hauret, I, Andant, N, Bonnin, A, Pereira, B, Coudeyre, E
BMJ open. 2016;(11):e011751
Abstract
INTRODUCTION Botulinum toxin injections are an effective treatment for limb spasticity following stroke. Different tracking techniques are used for this purpose: palpation, electrostimulation, electromyography and ultrasound. Yet very few studies have compared these different techniques, and none has successfully proved the superior efficacy of ultrasound-guided injections compared to another tracking method. The primary objective of our study was therefore to compare the efficacy of botulinum toxin injections depending on the tracking technique used: ultrasound versus electrostimulation. METHODS AND ANALYSIS This is a clinical, single-centre, prospective, interventional, single-blind, crossover, randomised trial. In total, 30 patients aged between 18 and 80 years presenting with triceps surae spasticity (evaluated >1 on the modified Ashworth scale) associated with hemiplegia sequelae due to stroke will be included. The patients will be selected among those who attend for consultation the Physical Medicine and Rehabilitation Department of the Clermont-Ferrand University Hospital. One group will receive the abobotulinumtoxinA (BoNT-A) injection guided by electrostimulation then ultrasound, and the second group's botulinum toxin injections will be guided by ultrasound then electrostimulation. For each patient, the duration of study participation is 5 months. The primary end point is variation in passive ankle dorsiflexion range of motion at slow and high speeds (Tardieu scale) with the knee straight. ETHICS AND DISSEMINATION This study received ethics approval form the CPP of Rhônes-Alpes region. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER NCT01935544; pre-results.
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Prolonging the duration of masseter muscle reduction by adjusting the masticatory movements after the treatment of masseter muscle hypertrophy with botulinum toxin type a injection.
Wei, J, Xu, H, Dong, J, Li, Q, Dai, C
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 2015;:S101-9
Abstract
BACKGROUND Botulinum toxin type A (BTX-A) is widely used for the clinical treatment of masseteric hypertrophy. Until now, few reports have discussed how to prolong the duration of its effectiveness. OBJECTIVE This study evaluated that purposely adjusting the masticatory movements is possible of postponing the masseter muscle rehypertrophy. METHODS Ninety-eight patients were randomly and equally divided into 2 groups, and 35 U BTX-A per side was injected into the masseters. The thickness and volume of the masticatory muscles were measured by ultrasound and computerized tomography, respectively. Patients in Group 1 were instructed to strengthen their masticatory effort during the denervated atrophic stage of the masseter (the interval was evaluated by real-time ultrasound monitoring), whereas patients in Group 2 were not given this instruction. When the masseter muscle began to recover, patients in both groups were instructed to reduce their chewing. RESULTS The duration of the masseter muscle rehypertrophy was significantly prolonged in Group 1 patients. The thickness and the volume of the other masticatory muscles were significantly increased in Group 1 but were either slightly decreased or insignificantly different in Group 2. CONCLUSION Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.