Post-stroke Spasticity Research Articles

Spasticity Matters: A Call to Action Following an Acute Stroke

More than half of survivors of stroke experience some degree of motor impairment, and spasticity can develop within days of the initial event. Patients with post-stroke spasticity (PSS) report a lower quality of life than those without spasticity, and they require regular long-term follow-up and monitoring within the healthcare system. This symposium supported a non-promotional discussion regarding the prevalence, burden, consequences, and need for identification of PSS. The benefits of PSS identification within 3 months of stroke were discussed by a panel of key opinion leaders, including Ted Wein, Neurologist and Assistant Professor of Neurology and Neurosurgery at McGill University, Montréal, Quebec, Canada; Ganesh Bavikatte, Consultant and Clinical Lead in rehabilitation medicine at the Walton Centre, Liverpool, and Honorary Senior Clinical Lecturer at the University of Liverpool, UK; and Sean Savitz, Professor of Neurology and Physical Medicine and Rehabilitation, Frank M. Yatsu MD Chair in Neurology, and Director of the Institute for Stroke and Cerebrovascular Diseases, University of Texas Health Science Center at Houston (UTHealth), Texas, US. These key opinion leaders explained that early prediction of PSS could be improved by increased awareness of the associated risk factors and tools, such as the Post-Stroke Checklist (PSC), the Spasticity Screening Tool, and the PSS Referral Tool. Finally, potential barriers to the early identification of PSS were presented, alongside strategies to overcome these barriers.

Analysis of neuroplasticity in post stroke spasticity: Serial MEP study

Analysis of neuroplasticity in post stroke spasticity: Serial MEP study

Analysis of MEP parameters in patients with post stroke spasticity in relation with RTMS therapy

Analysis of MEP parameters in patients with post stroke spasticity in relation with RTMS therapy

EE310 Botulinum Toxin Type a for the Treatment of Patients with Post-Stroke Focal Spasticity in Thailand: A Cost-Utility Analysis

EE310 Botulinum Toxin Type a for the Treatment of Patients with Post-Stroke Focal Spasticity in Thailand: A Cost-Utility Analysis

Selecting Goals and Target Muscles for Botulinum Toxin A Injection Using the Goal Oriented Facilitated Approach to Spasticity Treatment (GO-FAST) Tool.

The objective of this article is to introduce the GO-FAST Tool (developed by the Toxnet group) to clinicians working in the field of neurological rehabilitation, specifically post-stroke spasticity management. The concepts utilized in the Tool and described in this article can be broadly grouped into five topics: the principles of patient-centred goal-setting; an algorithm for setting SMART (specific, measurable, attainable, realistic, and timed) treatment goals; goal-related target muscles and botulinum toxin type A dose determinants; goal attainment follow-up, scoring, and interpretation; and the multimodal approach to spasticity management. The Tool can enhance clinical practice by providing guided assistance with goal-setting and target muscle selection for botulinum toxin type A treatment. It also provides support with the follow-up evaluation of goal attainment and calculation of treatment success. The Tool is designed to be used by clinicians with varying levels of expertise in the field of neurological rehabilitation and post-stroke spasticity management, from those who are new to the field to those with many years of experience. A case study is presented in the Results Section of the article to illustrate the utility of the Tool in setting SMART treatment goals in the management of patients with post-stroke spasticity.

Mirror therapy combined with neuromuscular electrical stimulation for poststroke lower extremity motor function recovery: a systematic review and meta-analysis

The combination of mirror therapy (MT) and neuromuscular electrical stimulation (NMES) has been devised as an intervention method in stroke rehabilitation; however, few studies have investigated its efficacy in lower extremity motor function recovery. In this systematic review and meta-analysis, we examined the effectiveness of combined MT and NMES therapy in improving poststroke walking speed, spasticity, balance and other gait parameters. Randomized controlled trials (RCTs) were selected from PubMed, Cochrane Library, EMBASE, and Scopus databases. In total, six RCTs which involving 181 participants were included. Our findings indicate that MT combined with NMES elicits greater improvement relative to control group in walking speed (SMD = 0.67, 95% confidence interval [CI] 0.26–1.07, P = 0.001), Berg Balance Scale (SMD = 0.72; 95% CI 0.31–1.13; P = 0.0007), cadence (SMD = 0.59, 95% CI 0.02–1.16, P = 0.04), step length (SMD = 0.94, 95% CI 0.35–1.53, P = 0.002), and stride length (SMD = 0.95, 95% CI 0.36–1.54, P = 0.002) but not in modified Ashworth scale (SMD = − 0.40, 95% CI − 1.05 to 0.26, P = 0.23). Our findings suggest that MT combined with NMES may be a suitable supplemental intervention to conventional therapy in stroke survivors.

The Improvement in Function of Poststroke Spasticity by Vibrational and Heated Stone-Needle Therapy and Meridian Dredging Exercise: A Randomized, Controlled, Preliminary Trial

Background: Poststroke spasticity (PSS) is a common complication of stroke. Current PSS treatments have been linked to high costs, lack of long-term effectiveness, and undesirable side effects. Vibrational and heated stone-needle therapy (VHS) has not been utilized to treat PSS, and its safety and effectiveness have yet to be proven by high-quality clinical research. Objective: The aim of this study was to determine the effectiveness of VHS combined with meridian dredging exercise (MDE) in patients with PSS. Methods: One hundred participants with stroke were included and randomly assigned to a treatment group (VHS plus MDEs) and a control group (MDEs alone). Patients in both groups were treated for 4 weeks. The primary outcome measures were the Modified Ashworth Scale (MAS) and Fugl-Meyer Assessment (FMA), while the secondary outcome measures were the Activity of Daily Living (ADL) Scale and Stroke-Specific Quality of Life Scale (SS-QOL). The evaluations were at baseline (T0) at 4 weeks of treatment (T1) and at 12 weeks of follow-up without treatment (T2). Results: At T1 and T2, there were significant differences in MAS between the two groups (p = 0.001). From the perspective of distribution, the VHS plus MDE group had significant changes, and the group-time interactions of upper and lower extremities in FMA, ADL, and SS-QOL were statistically significant (p < 0.001), indicating that patients’ symptoms improved after treatment. But the overall effect size is small, especially the effect size of improvement in SS-QOL at T1. Conclusion: VHS in combination with MDE can consistently alleviate PSS, enhance limb function, and improve the quality of life of patients with PSS. But we need to optimize the device further and observe the improvement of patients for a more extended period.

Testing spasticity mechanisms in chronic stroke before and after intervention with contralesional motor cortex 1 Hz rTMS and physiotherapy

BackgroundPrevious studies showed that repetitive transcranial magnetic stimulation (rTMS) reduces spasticity after stroke. However, clinical assessments like the modified Ashworth scale, cannot discriminate stretch reflex-mediated stiffness (spasticity) from passive stiffness components of resistance to muscle stretch. The mechanisms through which rTMS might influence spasticity are also not understood.MethodsWe measured the effects of contralesional motor cortex 1 Hz rTMS (1200 pulses + 50 min physiotherapy: 3×/week, for 4–6 weeks) on spasticity of the wrist flexor muscles in 54 chronic stroke patients using a hand-held dynamometer for objective quantification of the stretch reflex response. In addition, we measured the excitability of three spinal mechanisms thought to be related to post-stroke spasticity: post-activation depression, presynaptic inhibition and reciprocal inhibition before and after the intervention. Effects on motor impairment and function were also assessed using standardized stroke-specific clinical scales.ResultsThe stretch reflex-mediated torque in the wrist flexors was significantly reduced after the intervention, while no change was detected in the passive stiffness. Additionally, there was a significant improvement in the clinical tests of motor impairment and function. There were no significant changes in the excitability of any of the measured spinal mechanisms.ConclusionsWe demonstrated that contralesional motor cortex 1 Hz rTMS and physiotherapy can reduce the stretch reflex-mediated component of resistance to muscle stretch without affecting passive stiffness in chronic stroke. The specific physiological mechanisms driving this spasticity reduction remain unresolved, as no changes were observed in the excitability of the investigated spinal mechanisms.

Our Experience with rTMS in a Stroke

Background Repetitive Transcranial Magnetic Stimulation (r-TMS), a non-invasive brain stimulation method, appears promising in augmenting post-stroke recovery and requires further evaluation. Aims and Objective To study the effect of r-TMS treatment on motor function in patients with strokes of different duration and types. Methods A prospective, single center study was conducted to study the effect of bilateral motor cortex rTMS treatment in 100 consecutive patients with either ischemic or hemorrhagic stroke of any duration. Measured outcomes were changes in NIHSS, MRC grading for motor power, MAS (modified Ashworth scale) for spasticity and mRS (modified Rankin Score) from baseline to follow-up visit at 90 days. Paired T test was used for comparing the outcomes. Results 77% subjects were males, 82% had ischemic stroke, median age was 58.5 years, and median NIHSS score was 11. We observed favorable changes in outcome measures after treatment. mRS &lt; = 2 at 90 days was observed in 85.71% of patients with acute stroke, 64.51% of subacute and 55.88% of chronic strokes (p value &lt; 0.002). Acute stroke had higher rates of limb power improvement (94.28%) than subacute (70.96%) or chronic strokes (41.17%) (p value = &lt; 0.01). Post-stroke spasticity reduction was also observed after rTMS. Patients with infarcts or hemorrhages had no significant differences. No significant adverse events were seen. Conclusion rTMS appears to be safe in our study population and could be effectively delivered at different time points to augment post-stroke motor recovery.

Developments in Post-Stroke Spasticity Care with Early Use of Botulinum Toxin A: A Review

Spasticity is one of the most common and disabling complications of stroke. Most of these patients notably experience both muscle-based and non-muscle-based pain. This negatively affects their quality of life as well as aggravates caregiver burden. Post-stroke spasticity (PSS) may furthermore lead to several complications related to limited mobility, both motor (eg, contractures) and non-motor (cognitive decline, depression) if left untreated. It is thus crucial to address this with safe and effective means such as botulinum toxin therapy as early as possible. We aim to demonstrate the utility of botulinum toxin (BoNT) in PSS treatment and how early intervention may be preferable to late spasticity control for patients. Literature search and evaluation were done using the traditional evidence hierarchy. Early intervention with botulinum toxin A (BoNTA) demonstrated a more marked reduction in both spasticity and spasticity-related pain with longer required intervals to reinjection. Keywords: Botulinum Toxin, Early Use/Intervention, Poststroke Spasticity, Pain

Healthcare resource utilization and costs among patients with post-stroke spasticity before and after spasticity management including onabotulinumtoxina.

Real-world data regarding the impact of onabotulinumtoxinA on healthcare resource utilization and costs for post-stroke spasticity are scarce. To compare differences in 12-month healthcare resource utilization and costs before and after post-stroke spasticity management including onabotulinumtoxinA. This retrospective claims analysis of IBM MarketScan Commercial and Medicare Supplemental databases included adults with ≥ 1 onabotulinumtoxinA claim for post-stroke spasticity (1 January 2010 to 30 June 2018) and continuous enrolment for ≥ 12 months pre- and post-index (first onabotulinumtoxinA claim date). All-cause and spasticity-related healthcare resource utilization and costs were compared 12 months pre- and post-index (McNemar's χ2 test or paired t-test). A subgroup analysis assessed effect of stroke-to-index interval on costs. Among 735 patients, mean (standard deviation) stroke-date-to-index-date interval was 284.5 (198.8) days. Decreases were observed post-index for mean all-cause outpatient (62.9 vs 60.5; p ≤ 0.05) and emergency department visits (1.1 vs 0.8; p ≤ 0.0001), and hospital admissions (1.5 vs 0.4; p ≤ 0.0001). Increase in prescription fills (43.0 vs 53.7) was seen post-index. Post-index decreases in all-cause (-66%) and spasticity-related (-51%) costs were driven by reduced inpatient care costs. Findings were consistent regardless of stroke-date-to-index-date interval. Significant reductions in healthcare resource utilization and costs were observed after 1 year of post-stroke spasticity management including onabotulinumtoxinA. Long-term studies are needed to establish causality.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats.

To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

Clinical efficacy of ultrasound-guided stellate ganglion block combined with extracorporeal shock wave therapy on limb spasticity in patients with ischemic stroke

IntroductionTo observe the clinical efficacy of ultrasound-guided stellate ganglion block (SGB) + extracorporeal shock wave therapy (ESWT) for limb spasticity in patients with ischemic stroke.MethodsA total of 60 patients with post-stroke limb spasticity in our hospital were selected and randomly divided into four groups (n = 15). In the control group, patients received routine rehabilitation training. Based on routine rehabilitation training, SGB group patients underwent ultrasound-guided SGB, ESWT group patients received ESWT, and SGB + ESWT group patients received ultrasound-guided SGB combined with ESWT. The total treatment course was one month. The Modified Barthel Index (MBI) score, Fugl-Meyer Assessment and upper limb rehabilitation training system were applied to evaluate the activities of daily living, upper limb motor function and upper limb performance before and after treatment. Finally, the improvement after treatment was compared among different groups.ResultsAfter treatment, compared with the control group, the MBI score and the upper limb score based on Fugl-Meyer Assessment in the SGB, ESWT, and SGB + ESWT groups were significantly increased (P < 0.05). Furthermore, compared with the SGB and ESWT groups, SGB + ESWT exhibited a higher upper limb function score (P < 0.05), while the MBI score was not significantly different (P > 0.05). In terms of upper limb performance ability, patients in the SGB, ESWT and SGB + ESWT groups had better fitting degree, participation and exertion of exercise than those in the control group, and the SGB + ESWT group patients had the same movement trajectory as robots.ConclusionUltrasound-guided SGB and ESWT can reduce the muscle tension of patients, alleviate spasticity, promote the motor function of the upper limb, and improve the working performance of patients. However, the effect of SGB combined with ESWT is better.

Wet cupping with rehabilitation training for upper-limb poststroke spasticity: A systematic review and meta-analysis of randomized controlled trials

BackgroundUpper-limb poststroke spasticity (PSS) negatively impacts on patients’ quality of life. An increasing number of clinical trials have indicated that wet cupping with rehabilitation training is conductive to alleviate spastic muscle tone, thereby to improve upper-limb function. However, related evidence base is insufficient. This study systematically investigates the efficacy and safety of wet cupping with rehabilitation training on stroke patients with upper-limb spasticity. MethodsEight separate databases and two clinical trial registries were searched from their inception to December 6, 2022. Two reviewers extracted the data and assessed the quality of the literature, independently. The mean difference (MD) or risk ratio (RR) were used as measure of effect size in meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used for the certainty of evidence. ResultsEight randomized controlled trials (RCTs) were quantified for meta-analysis. The results indicated that in comparison with the control group, wet cupping with rehabilitation training was more effective in reducing modified Ashworth scale score (MD = −0.60, 95% CI: −0.74, −0.46; P < 0.00001) and the integral electromyography value of biceps muscle (MD = −4.71, 95% CI: −6.74, −2.67; P < 0.00001), but improving effective rate (RR = 1.28, 95% CI: 1.15, 1.41; P < 0.00001), Fugl-Myer Assessment score (MD = 4.84, 95% CI: 3.05, 6.64; P < 0.00001) as well as Barthel Index score (MD = 6.38, 95% CI: 2.20, 10.57; P = 0.003). However, no significant difference was found regarding the integral electromyography value of triceps muscle between groups (MD = 1.72, 95% CI: −2.05, 5.48; P = 0.37). ConclusionWet cupping with rehabilitation training should be included in a comprehensive therapeutic regimen for stroke patients with upper-limb spasticity. However, these results need to be further verified by more RCTs with rigorous design and large sample size.

Emerging theory of sensitization in post-stroke muscle spasticity.

Spasticity, characterized by a velocity-dependent increase in muscle tone and exaggerated reflexes, is a common complication in individuals with upper motor neuron syndrome, such as stroke survivors. Sensitization, the heightened responsiveness of the nervous system to sensory stimuli, has emerged as a potential cause of spasticity. This perspective article explores three emerging treatments targeting sensitization. Recent studies have investigated novel treatment modalities for spasticity, including Extracorporeal Shockwave Therapy (ESWT), repetitive peripheral magnetic stimulation (rPMS), and needling. ESWT has shown promising results in reducing spasticity in both the upper and lower extremities, potentially through mechanisms such as nitric oxide production, rheological property changes, and neuromuscular transmission dysfunction. rPMS offers a non-invasive approach that may reduce spasticity by increasing sensory input, enhancing cortical activation, and exerting tissue-softening effects. Needling has also demonstrated positive effects on spasticity reduction. The high heterogeneity observed indicates the need for more rigorous research to confirm these findings. Recently, mechanical needling and sterile water injection invented by the author is also promising for reducing spasticity through removing sensitization. In conclusion, the emerging treatment options discussed in this perspective article provide promising avenues for addressing sensitization in spasticity and improving motor function. However, further research is needed to validate their findings, optimize treatment protocols, and investigate their long-term effects on motor recovery and overall quality of life in individuals with spasticity.

Relief of post-stroke spasticity with acute vibrotactile stimulation: controlled crossover study of muscle and skin stimulus methods.

Prior work suggests that vibratory stimulation can reduce spasticity and hypertonia. It is unknown which of three predominant approaches (stimulation of the spastic muscle, antagonist muscle, or cutaneous regions) most reduces these symptoms. Determine which vibrotactile stimulation approach is most effective at reducing spastic hypertonia among post-stroke patients. Sham-controlled crossover study with random assignment of condition order in fourteen patients with post-stroke hand spasticity. All patients were studied in four conditions over four visits: three stimulation conditions and a sham control. The primary outcome measure was the Modified Ashworth Scale, and the secondary outcome measure was the Modified Tardieu Scale measured manually and using 3D motion capture. For each condition, measures of spastic hypertonia were taken at four time points: baseline, during stimulation, after stimulation was removed, and after a gripping exercise. A clinically meaningful difference in spastic hypertonia was found during and after cutaneous stimulation of the hand. Modified Ashworth and Modified Tardieu scores were reduced by a median of 1.1 (SD = 0.84, p = 0.001) and 0.75 (SD = 0.65, p = 0.003), respectively, during cutaneous stimulation, and by 1.25 (SD = 0.94, p = 0.001) and 0.71 (SD = 0.67, p = 0.003), respectively, at 15 min after cutaneous stimulation. Symptom reductions with spastic muscle stimulation and antagonist muscle stimulation were non-zero but not significant. There was no change with sham stimulation. Cutaneous vibrotactile stimulation of the hand provides significant reductions in spastic hypertonia, compared to muscle stimulation. www.ClinicalTrials.gov, identifier: NCT03814889.

Botulinum toxin use in patients with post-stroke spasticity: a nationwide retrospective study from France.

Current guidelines recommend intramuscular botulinum toxin type A (BoNT-A) injection as first-line treatment for spasticity, a frequent and impairing feature of various central nervous system (CNS) lesions such as stroke. Patients with spasticity commonly require BoNT-A injections once every 3 to 4 months. We conducted a nationwide, population-based, retrospective cohort study, using the French National Hospital Discharge Database (PMSI), to describe BoNT-A use for spasticity in clinical practice in France between 2014 and 2020. The PMSI database covers the whole French population, corresponding to over 66 million persons. We first searched the PMSI database for healthcare facility discharge of patients who received BoNT-A injections between 2014 and 2020, corresponding to the first set. For each BoNT-A-treated patient, we identified the medical condition for which BoNT-A may have been indicated. Another search of the PMSI database focused on patients admitted for acute stroke between 2014 and 2016 and their spasticity-related care pathway (second set). Overall, two subpopulations were analysed: 138,481 patients who received BoNT-A injections between 2014 and 2020, and 318,025 patients who survived a stroke event between 2014 and 2016 and were followed up until 2020. Among the 138,481 BoNT-A-treated patients, 53.5% received only one or two BoNT-A injections. Most of these patients (N = 85,900; 62.0%) received BoNT-A because they had CNS lesions. The number of patients with CNS lesions who received ≥1 BoNT-A injection increased by a mean of 7.5% per year from 2014 to 2019, but decreased by 0.2% between 2019 and 2020, corresponding to the COVID-19 outbreak. In stroke survivors (N = 318,025), 10.7% were coded with post-stroke spasticity, 2.3% received ≥1 BoNT-A injection between 2014 and 2020, and only 0.8% received ≥3 injections within the 12 months following BoNT-A treatment initiation, i.e., once every 3 to 4 months. Our analysis of the exhaustive PMSI database showed a suboptimal implementation of BoNT-A treatment recommendations in France. BoNT-A treatment initiation and re-administration are low, particularly in patients with post-stroke spasticity. Further investigations may help explain this observation, and may target specific actions to improve spasticity-related care pathway.

Immediate Effects of Anti-Spastic Epidural Cervical Spinal Cord Stimulation on Functional Connectivity of the Central Motor System in Patients with Stroke- and Traumatic Brain Injury-Induced Spasticity: A Pilot Resting-State Functional Magnetic Resonance Imaging Study.

Spinal cord stimulation (SCS) is one approach to the potential improvement of patients with post-stroke or post-traumatic spasticity. However, little is known about whether and how such interventions alter supraspinal neural systems involved in the pathogenesis of spasticity. This pilot study investigated whether epidural spinal cord stimulation at the level of the C3-C5 cervical segments, aimed at reducing spasticity, alters the patterns of functional connectivity of the brain. Eight patients with spasticity in the right limbs as a result of left cerebral hemisphere damage (due to hemorrhagic and ischemic stroke or traumatic and anoxic brain injury) were assessed with fMRI immediately before and immediately after short-term (1 to 6 days) test cervical epidural SCS therapy. Eight demographically and clinically comparable patients with spasticity in the right extremities due to a left hemisphere ischemic stroke and brain injury who received conventional therapy were examined as a control group. All patients also had paresis of one or two limbs and hyperreflexia. After the SCS therapy, there were three main findings: (1) higher functional connectivity of the brainstem to the right premotor cortex and changes in functional connectivity between cortical motor areas, (2) increased functional connectivity between the right and left lateral nodes of the sensorimotor network, and (3) a positive correlation between decreased spasticity in the right leg and increased functional connectivity within the right hemisphere sensorimotor cortex. All these changes in functional connectivity occurred with a statistically significant decrease in spasticity, as assessed using the modified Ashworth scale. The control group showed no decrease in spasticity or increase in functional connectivity in any of the seeds of interest. On the contrary, a decrease in functional connectivity of the brainstem and right postcentral gyrus was observed in this group during the observation period. We were thus able to detect intrinsic brain connectivity rearrangements that occurred during spasticity mitigation following short epidural SCS therapy. The clinical results obtained confirmed the efficacy of short-term anti-spastic SCS therapy. The obtained data on functional rearrangements of the central motor system may shed light on the mechanism of antispastic action of this procedure.

Effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on the pharmacokinetics of tolperisone.

Tolperisone, a muscle relaxant used for post-stroke spasticity, is metabolized to its main metabolite by CYP2D6 and to a lesser extent by CYP2C19 and CYP1A2. We investigated the effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on tolperisone pharmacokinetics. A 150mg oral dose of tolperisone was given to 184 healthy Korean subjects and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 3.14-fold significant increase in AUC0-∞ was observed in the CYP2D6*10/*10 group compared with the CYP2D6*wt/*wt group, whereas a 3.59-fold increasein AUC0-∞ was observed in CYP2C19PMs compared to CYP2C19EMs. Smokers had a 38.5% decrease in AUC0-∞ when compared to non-smokers. When these effects were combined, CYP2D6*10/*10-CYP2C19PM-Non-smokers had a 25.9-fold increase in AUC0-∞ compared to CYP2D6*wt/*wt-CYP2C19EM-Smokers. Genetic polymorphisms of CYP2D6 and CYP2C19 and cigarette smoking independently and significantly affected tolperisone pharmacokinetics and these effects combined resulted in a much greater impact on tolperisone pharmacokinetics.

Artículo traducido] Revisión sistemática y coste-efectividad del tratamiento con abobotulinumtoxinA para la espasticidad postictus en comparación con la fisioterapia

ObjectivePost-stroke spasticity is a common complication in stroke survivors, causing severe burden to patients living with it. The aim of this review was to conduct a cost-effectiveness analysis (CEA) of the treatment of post-stroke spasticity, in adults, with abobotulinumtoxinA compared to the best supportive care, based on results from a systematic literature review. Given that abobotulinumtoxinA (aboBoNT-A) is always accompanied by the best supportive care treatment, the CEA compared aboBoNT-A plus the best supportive care with the best supportive care alone. MethodsA systematic literature review in EMBASE (including Medline and PubMed), Scopus, and other sources (Google Scholar) was conducted. Articles of all types, providing information on the costs and/or effectiveness measures for the current treatments of post-stroke spasticity in adults were included. The synthesis of information from the review provided the parameters for the design of a CEA of the mentioned treatment of interest. The societal perspective was compared to a perspective where only direct costs were observed. ResultsIn total, 532 abstracts were screened. Full information was revised from 40 papers and 13 of these were selected as core papers for full data extraction. Data from the core publications formed the basis for the development of a cost-effectiveness model. In all the included papers physiotherapy was the best supportive care treatment. The cost-effectiveness analysis showed that even in the most conservative scenario, assuming the worst case scenario, the probability of a cost per quality-adjusted life-year (QALY) gained below €40,000, for aboBoNT-A together with physiotherapy is above 0.8, and with certainty below €50,000/QALY when either a direct costs, or a societal perspective was taken. On average, the probabilistic model obtains a negative mean incremental cost-effectiveness ratio of around −15,000 €/QALY. ConclusionThe cost-effectiveness analyses show that aboBoNT-A together with physiotherapy would be a cost-effective treatment compared with physiotherapy alone, independently of the perspective considered.