Canadian Stroke Best Practice Recommendations, 7th Edition: Cerebral Venous Thrombosis, 2024.

The 7th edition of the Canadian Stroke Best Practice Recommendations (CSBPR) is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners, and intended to drive healthcare excellence, improved outcomes and more integrated health systems. This edition includes a new module on the management of cerebral venous thrombosis (CVT). Cerebral venous thrombosis is defined as thrombosis of the veins of the brain, including the dural venous sinuses and/or cortical or deep veins. Cerebral venous thrombosis is a rare but potentially life-threatening type of stroke, representing 0.5-1.0% of all stroke admissions. The reported rates of CVT are approximately 10-20 per million and appear to be increasing over time. The risk of CVT is higher in women and often associated with oral contraceptive use and with pregnancy and the puerperium. This guideline addresses care for adult individuals who present to the healthcare system with current or recent symptoms of CVT. The recommendations cover the continuum of care from diagnosis and initial clinical assessment of symptomatic CVT, to acute treatment of symptomatic CVT, post-acute management, person-centered care, special considerations in the long-term management of CVT, including pregnancy and considerations related to CVT in special circumstances such as trauma and vaccination. This module also includes supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Spasticity Management Teams, Evaluations, and Tools: A Canadian Cross-Sectional Survey.

OBJECTIVE: The objective of this study is to determine the physical evaluations and assessment tools used by a group of Canadian healthcare professionals treating adults with spasticity. METHODS: A cross-sectional web-based 19-question survey was developed to determine the types of physical evaluations, tone-related impairment measurements, and assessment tools used in the management of adults with spasticity. The survey was distributed to healthcare professionals from the Canadian Advances in Neuro-Orthopedics for Spasticity Congress database. RESULTS: Eighty study participants (61 physiatrists and 19 other healthcare professionals) completed the survey and were included. Nearly half (46.3%, 37/80) of the participants reported having an inter- or trans-disciplinary team managing individuals with spasticity. Visual observation of movement, available range of motion determination, tone during velocity-dependent passive range of motion looking for a spastic catch, spasticity, and clonus, and evaluation of gait were the most frequently used physical evaluations. The most frequently used spasticity tools were the Modified Ashworth Scale, goniometer, and Goal Attainment Scale. Results were similar in brain- and spinal cord-predominant etiologies. To evaluate goals, qualitative description was used most (37.5%). CONCLUSION: Our findings provide a better understanding of the spasticity management landscape in Canada with respect to staffing, physical evaluations, and outcome measurements used in clinical practice. For all etiologies of spasticity, visual observation of patient movement, Modified Ashworth Scale, and qualitative goal outcomes descriptions were most commonly used to guide treatment and optimize outcomes. Understanding the current practice of spasticity assessment will help provide guidance for clinical evaluation and management of spasticity.

International Recommendations to Manage Poststroke Equinovarus Foot Deformity Validated by a Panel of Experts Using Delphi.

OBJECTIVE: To establish international recommendations for the management of spastic equinovarus foot deformity. DESIGN: Delphi method. SETTING: International study. PARTICIPANTS: A total of 24 international experts (N=24) in neuro-orthopedic deformities, from different specialties (Physical and Rehabilitation Medicine physicians, neurologists, geriatricians, orthopedic surgeons, neurosurgeons, plastic surgeons). INTERVENTIONS: Experts answered 3 rounds of questions related to important aspects of diagnosis, assessment, and treatment of spastic equinovarus foot deformity. MAIN OUTCOME MEASURES: A consensus was established when at least 80% of experts agreed on a statement RESULTS: A total of 52 items reached consensus. Experts recommend assessing effect of the deformity on functional activities before treatment. Before treatment, it is crucial to differentiate spastic muscle overactivity from soft tissue contractures, identify which muscles are involved in the deformity, and evaluate the activity of antagonist muscles. Motor nerve blocks, 2-dimensional video analysis, and radiologic examinations are often required to complement a clinical examination. The treatment of equinovarus foot depends on the correctability of the deformity and the patient's ability to stand or walk. The preoperative assessment should include an interdisciplinary consultation that must finalize a formal agreement between physicians and the patient, which will define personalized attainable goals before surgery. CONCLUSION: The establishment of guidelines on managing equinovarus foot will help physicians and surgeons, specialists, and nonspecialists to diagnoses and assess the deformity and direct patients to a network of experts to optimize patient functional recovery and improve their autonomy.

Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

New View on the Canadian Burden of Stroke: Productivity Loss in Adults Who Return to Work.

An often overlooked facet of the indirect costs affecting working-age stroke survivors is the challenges experienced by those who return to work. This study quantified the productivity loss in 20 stroke survivors who returned to work which amounted to 53.0 missed work days and an average indirect cost of $10,298 (CAD) in the year following a stroke. Despite the quantified productivity loss, 75% of patients reported no significant disability and a high proportion were self-employed compared to the Canadian population, indicating that socioeconomic factors may be driving patient decisions to return to work.

Adherence to Guidelines at a Stroke Prevention Clinic: A Follow-up Study.

BACKGROUND: In 2010, we published our stroke prevention clinic's performance as compared to Canadian stroke prevention guidelines. We now compare our clinic's adherence with guidelines to our previous results, following the implementation of an electronic documentation form. METHODS: All new patients referred to our clinic (McGill University Health Center) for recent transient ischemic attack (TIA) or ischemic stroke between 2014 and 2017 were included. We compared adherence to guidelines to our previous report (N=408 patients for period 2008-2010) regarding vascular risk management and treatment. RESULTS: Three hundred and ninety-two patients were included, of which 36% had a TIA and 64% had an ischemic stroke, with a mean age of 70 years and 43% female. Although the more recent cohort has shown a higher proportion of cardioembolic stroke compared to previous (19.1% vs. 14.7%) following new guidelines regarding prolonged cardiac monitoring, increased popularity in CT angiography has not translated into greater proportion of large-artery stroke subtype (26.3% vs. 26.2%). Blood pressure (BP) targets were achieved in 83% compared with 70% in our previous report (p<0.01). Attainment of low-density lipoprotein cholesterol target was also improved in our recent study (66% vs. 46%, p<0.01). No significant difference was found in the consistency of antithrombotic use (97.7% vs. 99.8%, p=0.08). However, there was a decline in smoking cessation (35% vs. 73%, p=0.02). Overall, optimal therapy status was better attained in the present cohort compared to the previous one (52% vs. 22%, p<0.01). The male sex was associated with better attainment of optimal therapy status (odds ratio, 1.61; 95% confidence interval, 1.04-2.51). The number of follow-up visits and the length of follow-up were not associated with attainment of stroke prevention targets. CONCLUSIONS: Our study shows improvement in attainment of therapeutic goals as recommended by Canadian stroke prevention guidelines, possibly attributed in part to the implementation of electronic medical recording in our clinic. Areas for improvement include smoking cessation counseling and diabetes screening.

CONTEXTE: En 2010, nous avons rendu publics les résultats de notre clinique de prévention des AVC en ce qui regarde les lignes directrices canadiennes de prévention des AVC. Suite à la mise en place d'un formulaire d'information électronique, nous voulons maintenant comparer l'adhésion actuelle de notre clinique à ces lignes directrices à celle mesurée en 2010. MÉTHODES: Tous les nouveaux patients adressés à notre clinique (Centre universitaire de santé McGill) pour des cas récents d'ischémie cérébrale transitoire (ICT) ou d'AVC ischémique survenus entre 2014 et 2017 ont été inclus dans cette étude. Nous avons ainsi comparé l'adhésion actuelle aux lignes directrices évoquées ci-haut à celle du précédent rapport (N = 408 patients pour la période allant de 2008 à 2010), et ce, en ce qui concerne la prise en charge du risque vasculaire et les traitements nécessaires. RÉSULTATS: Au total, 392 patients ont été inclus; de ce nombre, 36 % d'entre eux avaient été victimes d'ICT tandis que 64 % avaient été victimes d'un AVC ischémique. Leur âge moyen était de 70 ans et 43 % d'entre eux étaient de sexe féminin. Bien que la cohorte la plus récente, à la suite de l'introduction de nouvelles lignes directrices portant sur la surveillance cardiaque prolongée, ait donné à voir une proportion plus élevée d'AVC d'origine cardio-embolique comparativement à la précédente (19,1 % par opposition à 14,7 %), la popularité croissante de l'angiographie par tomodensitométrie ne s'est pas traduite par une proportion plus grande de sous-types d'AVC affectant de grandes artères (26,3 % de 2014 à 2017 par opposition à 26,2 % de 2008 à 2010). Les valeurs cibles fixées en matière de pression artérielle ont été atteintes dans 83 % des cas comparativement à 70 % des cas dans notre rapport précédent (p < 0,01). L'atteinte de la valeur cible en ce qui concerne le taux de LDL-cholestérol (lipoprotéines de faible intensité) a également été améliorée dans notre plus récent rapport (66 % par opposition à 46 %; p < 0,01). Ajoutons aussi qu'aucune différence notable n'a été observée quant à une utilisation constante d'anti-thrombotiques (97,7 % par opposition à 99,8 %; p = 0,08). Fait à souligner, un déclin dans l'abandon du tabagisme a été noté (35 % par opposition à 73%; p = 0,02). Dans l'ensemble, les conditions d'une guérison optimale (optimal therapy status) ont été davantage atteintes dans la cohorte la plus récente comparativement à celle de 2008 à 2010 (52 % par opposition à 22 %; p < 0,01). Le fait d'être de sexe masculin a été associé à de meilleures conditions de guérison optimale (rapport des cotes: 1,61; IC 95 %, 1,04 ­ 2,51). Enfin, mentionnons que le nombre de consultations de suivi et la durée des suivis n'ont pas été associés à l'atteinte de valeurs cibles en matière de prévention des AVC. CONCLUSIONS: Notre étude montre une série d'améliorations dans l'atteinte des objectifs thérapeutiques recommandés par les lignes directrices canadiennes de prévention des AVC. Cela pourrait être en partie attribuable à la mise en place de dossiers médicaux informatisés au sein de notre clinique. Parmi les aspects qui méritent une amélioration, citons l'établissement d'un programme de counseling en ce qui regarde l'abandon du tabagisme et le dépistage du diabète.

Long-term Safety and Dosing of OnabotulinumtoxinA: A Prospective, Observational Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Dosage et sécurité à long terme de l'onabotulinumtoxinA : une étude prospective et observationnelle. Contexte : Bien que les traitements thérapeutiques soient destinés à soulager les symptômes associés à une maladie, il importe d'examiner avec grand soin leur sécurité et d'en assurer un suivi afin de maintenir un rapport bénéfice/risque qui soit positif. L'objectif de MOBILITY a donc été d'étudier la sécurité à long terme de l'onabotulinumtoxinA dans le traitement de plusieurs indications thérapeutiques. Méthodes : Nous avons ainsi fait appel à une étude canadienne prospective et observationnelle menée dans plusieurs centres de santé. Dans cette étude de phase IV, des patients ont été traités avec l'onabotulinumtoxinA en vertu d'indications thérapeutiques. Ce sont des médecins participants qui en avaient déterminé le dosage. De plus, tout événement indésirable a été noté en cours d'étude. Résultats : Au total 1372 patients ont été inclus dans cette cohorte (n = 1372). Ces patients étaient atteints des troubles suivants : spasticité focale chez l'adulte, blépharospasme, infirmité motrice cérébrale, dystonie cervicale, spasmes hémifaciaux, hyperhidrose, etc. On a signalé chez 83 patients, soit 6 % d'entre eux, des événements indésirables. On a aussi estimé que 44 événements indésirables ayant affecté 24 patients (2 %) étaient reliés au traitement proprement dit. Ajoutons que 38 patients (3 %) ont signalé avoir été victimes d'événements indésirables et que 10 événements indésirables ont été reliés au traitement chez 5 patients (0,4 %). Enfin, les événements indésirables les plus communément signalés ont été la faiblesse musculaire (n = 7/44) et la dysphagie (n = 6/44). Conclusions : Dans le cas de patients ayant bénéficié de six traitements ou moins avec l'onabotulinumtoxinA, des événements indésirables ont été signalés chez < 2 % d'entre eux au cours des presque cinq prochaines années. Tirés de MOBILITY, nos résultats apportent une preuve additionnelle que les traitements avec l'onabotulinumtoxinA sont à long terme sécuritaires dans le cas de nombreuses indications thérapeutiques.

A Delphi-Based Consensus Statement on the Management of Anticoagulated Patients With Botulinum Toxin for Limb Spasticity.

OBJECTIVE: To create a consensus statement on the considerations for treatment of anticoagulated patients with botulinum toxin A (BoNTA) intramuscular injections for limb spasticity. DESIGN: We used the Delphi method. SETTING: A multiquestion electronic survey. PARTICIPANTS: Canadian physicians (N=39) who use BoNTA injections for spasticity management in their practice. INTERVENTIONS: After the survey was sent, there were e-mail discussions to facilitate an understanding of the issues underlying the responses. Consensus for each question was reached when agreement level was ≥75%. MAIN OUTCOME MEASURES: Not applicable. RESULTS: When injecting BoNTA in anticoagulated patients: (1) BoNTA injections should not be withheld regardless of muscles injected; (2) a 25G or smaller size needle should be used when injecting into the deep leg compartment muscles; (3) international normalized ratio (INR) level should be ≤3.5 when injecting the deep leg compartment muscles; (4) if there are clinical concerns such as history of a fluctuating INR, recent bleeding, excessive or new bruising, then an INR value on the day of injection with point-of-care testing or within the preceding 2-3 days should be taken into consideration when injecting deep compartment muscles; (5) the concern regarding bleeding when using direct oral anticoagulants (DOACs) should be the same as with warfarin (when INR is in the therapeutic range); (6) the dose and scheduling of DOACs should not be altered for the purpose of minimizing the risk of bleeding prior to BoNTA injections. CONCLUSIONS: These consensus statements provide a framework for physicians to consider when injecting BoNTA for spasticity in anticoagulated patients. These consensus statements are not strict guidelines or decision-making steps, but rather an effort to generate common understanding in the absence of evidence in the literature.

Real-World, Long-Term Quality of Life Following Therapeutic OnabotulinumtoxinA Treatment.

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.

An open-label trial of a sumatriptan auto-injector for migraine in patients currently treated with subcutaneous sumatriptan.

OBJECTIVE: To assess the ability of patients, during an acute migraine attack, to successfully self-inject a single dose of sumatriptan using a novel sumatriptan auto-injector (Alsuma(®)), and to evaluate the safety, tolerability, and effectiveness of this sumatriptan auto-injector during an acute migraine attack. BACKGROUND: This sumatriptan auto-injector is a single-use system for the rapid subcutaneous delivery of 6 mg of sumatriptan succinate in the acute management of migraine pain. This auto-injector was developed to address the clinical need for an easy-to-use and rapid-to-administer system that did not require any assembly during the time of an ongoing attack. METHODS: This was an open-label, phase 3 trial conducted at 10 sites in the USA. Male or female adults, ages 18-60 years old, were eligible for study entry if they met International Headache Society criteria for migraine with or without aura, with at least 2 attacks per month, and if they reported use of subcutaneous injectable sumatriptan on at least 2 occasions within the previous 2 months. During the onset of a migraine attack of moderate-to-severe intensity, patients were asked to administer a 6-mg subcutaneous dose of sumatriptan using the auto-injector. Patients returned to the study site within 72 hours of the migraine for the post-treatment assessment visit. RESULTS: A total of 63 patients met entry criteria and received a dose of study medication (the intent-to-treat sample). Sixty-one patients (96.8%) reported injection in the thigh, and 2 patients (3.2%) reported injection in the arm. On the patient questionnaire, 100% of patients (95% confidence interval [CI] 94.3-100%) "agreed" or "agreed strongly" that the written instructions for the auto-injector were clear and easy to follow (30.2% "agreed"; 69.8% "agreed strongly"); 95.2% of patients (95% CI 86.7-99.0%) found that the auto-injector was easy to use (36.5% "agreed"; 58.7% "agreed strongly"), and 65.1% of patients (95% CI 52.0-76.7%) stated that they preferred the new auto-injector to the traditional auto-injector that they were using prior to study entry (42.9% "agreed"; 22.2% "agreed strongly"). Headache response rate at 2 hours was 93.7% (95% CI 84.5-98.2%), and pain-free rate at 2 hours was 60.3% (95% CI 47.2-72.4%). Pain-free rates at 2 hours were similarly high (58.3%; 95% CI 36.6-77.9%) in the subgroup of patients reporting severe baseline headache pain. Only 1 patient reported use of rescue medication after use of the auto-injector, a single oral dose of sumatriptan 100 mg on the same day. The most frequent adverse event was injection site bruising, reported by 15.9% of patients, and rated in all instance as mild in intensity. The second most frequent adverse event was injection site pain, reported by 6.3% of patients, and rated as mild by all patients except 1, who rated it as moderate in intensity. CONCLUSION: The majority of injection-experienced patients reported the pre-assembled, single-use sumatriptan auto-injector to be an easy-to-use, preferred treatment for an acute migraine attack. The study found the auto-injector to be safe and well tolerated, with levels of injection site reactions that were mild and infrequent.

Treatment of adult spasticity with Botox (onabotulinumtoxinA): Development, insights, and impact.

Upper and lower limb spasticity (ULS, LLS) often occur following a stroke or in patients with other neurological disorders, leading to difficulties in mobility and daily living and decreased quality of life. Prior to the use of onabotulinumtoxinA, antispastic medications had limited efficacy and often caused sedation. Phenol injections were difficult for physicians to perform, painful, and led to tissue destruction. The success of onabotulinumtoxinA in treating cervical dystonia led to its use in spasticity. However, many challenges characterized the development of onabotulinumtoxinA for adult spasticity. The wide variability in the presentation of spasticity among patients rendered it difficult to determine which muscles to inject and how to measure improvement. Another challenge was the initial refusal of the Food and Drug Administration to accept the Ashworth Scale as a primary endpoint. Additional scales were designed to incorporate a goal-oriented, patient-centered approach that also accounted for the variability of spasticity presentations. Several randomized, double-blind, placebo-controlled trials of post-stroke spasticity of the elbow, wrist, and/or fingers showed significantly greater improvements in the modified Ashworth Scale and patient treatment goals and led to the approval of onabotulinumtoxinA for the treatment of ULS in adult patients. Lessons learned from the successful ULS trials were applied to design an LLS trial that led to approval for the latter indication. Additional observational trials mimicking real-world treatment have shown continued effectiveness and patient satisfaction. The use of onabotulinumtoxinA for spasticity has ushered in a more patient-centered treatment approach that has vastly improved patients' quality of life.

BoNT-A for Post-Stroke Spasticity: Guidance on Unmet Clinical Needs from a Delphi Panel Approach.

There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based survey Delphi process to provide guidance that can support clinicians in the decision-making process. There was a broad consensus among physicians that BoNT-A intervention should be administered as soon as the spasticity interferes with the patients' clinical condition. Patients monitoring is needed over time, a follow-up of 4-6 weeks is considered necessary. Furthermore, physicians agreed that treatment should be offered irrespective of the duration of the spasticity. The Delphi consensus also stressed the importance of patient-centered goals in order to satisfy the clinical needs of the patient regardless of time of onset or duration of spasticity. The findings arising from this Delphi process provide insights into the unmet needs in managing post-stroke spasticity from the clinician's perspective and provides guidance for physicians for the utilization of BoNT-A for the treatment of post-stroke spasticity in daily practice.

Perspective of an International Online Patient and Caregiver Community on the Burden of Spasticity and Impact of Botulinum Neurotoxin Therapy: Survey Study.

BACKGROUND: Patient- and caregiver-reported data are lacking on the burden of spasticity, and the impact of botulinum neurotoxin type A (BoNT-A) treatment for this condition, on patients' daily lives. As recommended in recent guidance from the US Food and Drug Administration, online patient communities can represent a platform from which to gather specific information outside of a clinical trial setting on the burden of conditions experienced by patients and caregivers and their views on treatment options in order to inform evidence-based medicine and drug development. OBJECTIVE: The objective of our study is to characterize spasticity symptoms and their associated burdens on Western European and US patients and caregivers in the realms of work, daily activities, quality of life (QoL), as well as the positive and negative impacts of treatment with BoNT-A (cost, time, QoL) using Carenity, an international online community for people with chronic health conditions. METHODS: We performed a noninterventional, multinational survey. Eligible participants were 18 years old or older and had, or had cared for, someone with spasticity who had been treated with BoNT-A for at least 1 year. Patients and caregivers were asked to complete an internet-based survey via Carenity; caregivers reported their own answers and answered on behalf of their patients. Questions included the burden of spasticity on the ability to work, functioning, daily-living activities, and QoL, the impact of BoNT A therapy on patients' lives, and the potential benefits of fewer injections. RESULTS: There were 615 respondents (427 patients and 188 caregivers). The mean age of patients and caregivers was 41.7 years and 38.6 years, respectively, and the most commonly reported cause of spasticity was multiple sclerosis. Caregivers were most often the parents (76/188, 40%) or another family member (51/188, 27%) of their patients. Spasticity had a clear impact on patients' and caregivers' lives, including the ability to work and injection costs. For patients, spasticity caused difficulties with activities of daily living and reduced QoL indices. The median number of BoNT-A injections was 4 times per year, and 92% (393/427) of patients reported that treatment improved their overall satisfaction with life. Regarding the BoNT-A injection burden, the greatest patient-reported challenges were the cost and availability of timely appointments. Overall, 86% (368/427) of patients believed that a reduced injection frequency would be beneficial. Caregivers answering for their patients gave largely similar responses to those reported by patients. CONCLUSIONS: Spasticity has a negative impact on both patients' and caregivers' lives. All respondents reported that BoNT A treatment improved their lives, despite the associated challenges. Patients believed that reducing the frequency of BoNT-A injections could alleviate practical issues associated with treatment, implying that a longer-acting BoNT-A injection would be well received.

Optimal Muscle Selection for OnabotulinumtoxinA Injections in Poststroke Lower-Limb Spasticity: A Randomized Trial.

OBJECTIVE: The aim of the study was to identify optimal muscle selection patterns for onabotulinumtoxinA treatment of poststroke lower-limb spasticity. DESIGN: Adults with poststroke lower-limb spasticity (ankle Modified Ashworth Scale ≥3) were randomized to onabotulinumtoxinA (300 U, mandatory ankle plantar flexors; ≤100 U, optional lower-limb muscles) or placebo. Post hoc analysis assessed the impact of muscle selection patterns on ankle Modified Ashworth Scale and physician-assessed Clinical Global Impression of Change based on change from baseline to average of weeks 4/6 versus placebo. RESULTS: Among 468 patients randomized, onabotulinumtoxinA improved ankle Modified Ashworth Scale (-0.81 vs -0.61, P = 0.01) and Clinical Global Impression of Change (0.86 vs 0.65, P = 0.012) versus placebo. Injection of mandatory muscles alone was not sufficient in improving ankle Modified Ashworth Scale (P = 0.255) or Clinical Global Impression of Change (P = 0.576) versus placebo but was adequate 24 mos or less after stroke (Modified Ashworth Scale, -1.13 vs -0.62, P = 0.019; Clinical Global Impression of Change, 1.24 vs 0.68, P = 0.006). Additional injections into toe muscles (flexor digitorum longus, flexor hallucis longus) improved ankle Modified Ashworth Scale (-0.98 vs -0.52, P = 0.002) and Clinical Global Impression of Change (0.80 vs 0.38, P = 0.023) versus placebo regardless of time since stroke. OnabotulinumtoxinA was well tolerated, with no new safety findings. CONCLUSIONS: Post hoc analyses suggested additional injections of onabotulinumtoxinA into toe flexors improved ankle Modified Ashworth Scale and Clinical Global Impression of Change scores versus mandatory muscles alone overall and with treatment initiation more than 24 mos after stroke.

OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity: A Randomized Trial.

BACKGROUND: Poststroke distal lower limb spasticity impairs mobility, limiting activities of daily living and requiring additional caregiver time. OBJECTIVE: To evaluate the efficacy, safety, and sustained benefit of onabotulinumtoxinA in adults with poststroke lower limb spasticity (PSLLS). DESIGN: A multicenter, randomized, double-blind, phase 3, placebo-controlled trial (NCT01575054). SETTING: Sixty study centers across North America, Europe, Russia, the United Kingdom, and South Korea. PATIENTS: Adult patients (18-65 years of age) with PSLLS (Modified Ashworth Scale [MAS] ≥3) of the ankle plantar flexors and the most recent stroke ≥3 months before study enrollment. INTERVENTIONS: During the open-label phase, patients received ≤3 onabotulinumtoxinA treatments (≤400 U) or placebo at approximately 12-week intervals. Treatments were into the ankle plantar flexors (onabotulinumtoxinA 300 U into ankle plantar flexors; ≤100 U, optional lower limb muscles). MAIN OUTCOME MEASUREMENTS: The double-blind primary endpoint was MAS change from baseline (average score at weeks 4 and 6). Secondary measures included physician-assessed Clinical Global Impression of Change (CGI), MAS change from baseline in optional muscles, Goal Attainment Scale (GAS), and pain scale. RESULTS: Of 468 patients enrolled, 450 (96%) completed the double-blind phase and 413 (88%) completed the study. Small improvements in MAS observed with onabotulinumtoxinA during the double-blind phase (onabotulinumtoxinA, -0.8; placebo, -0.6, P = .01) were further enhanced with additional treatments through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, -1.2; placebo/onabotulinumtoxinA, -1.4). Small improvements in CGI observed during the double-blind phase (onabotulinumtoxinA, 0.9; placebo, 0.7, P = .01) were also further enhanced through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, 1.6; placebo/onabotulinumtoxinA, 1.6). Physician- and patient-assessed GAS scores improved with each subsequent treatment. No new safety signals emerged. CONCLUSIONS: OnabotulinumtoxinA significantly improved ankle MAS, CGI, and GAS scores compared with placebo; improvements were consistent and increased with repeated treatments of onabotulinumtoxinA over 1 year in patients with PSLLS. LEVEL OF EVIDENCE: I.