Mixtures of Intrinsically Disordered Neuronal Protein Tau and Anionic Liposomes Reveal Distinct Anionic Liposome-Tau Complexes Coexisting with Tau Liquid-Liquid Phase-Separated Coacervates.

Tau, an intrinsically disordered neuronal protein and polyampholyte with an overall positive charge, is a microtubule (MT) associated protein that binds to anionic domains of MTs and suppresses their dynamic instability. Aberrant tau-MT interactions are implicated in Alzheimer's and other neurodegenerative diseases. Here, we studied the interactions between full-length human protein tau and other negatively charged binding substrates, as revealed by differential interference contrast (DIC) and fluorescence microscopy. As a binding substrate, we chose anionic liposomes (ALs) containing either 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS, -1e) or 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG, -1e) mixed with zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) to mimic anionic plasma membranes of axons where tau resides. At low salt concentrations (0 to 10 mM KCl or NaCl) with minimal charge screening, reaction mixtures of tau and ALs resulted in the formation of distinct states of AL-tau complexes coexisting with liquid-liquid phase-separated tau self-coacervates arising from the polyampholytic nature of tau containing cationic and anionic domains. AL-tau complexes (i.e. tau-lipoplexes) exhibited distinct types of morphologies. This included large ∼20-30 µm tau-decorated giant vesicles with additional smaller liposomes with bound tau attached to the giant vesicles and tau-mediated finite-size assemblies of small liposomes. As the salt concentration was increased to near and above 150 mM for 1:1 electrolytes, AL-tau complexes remained stable, while tau self-coacervate droplets were found to dissolve, indicative of the breaking of (anionic/cationic) electrostatic bonds between tau chains due to increased charge screening. The findings are consistent with the hypothesis that distinct cationic domains of tau may interact with anionic lipid domains of the lumen-facing monolayer of the axon's plasma membrane, suggesting the possibility of transient yet robust interactions near relevant ionic strengths found in neurons.

Mixtures of Intrinsically Disordered Neuronal Protein Tau and Anionic Liposomes Reveal Distinct Anionic Liposome-Tau Complexes Coexisting with Tau Liquid-Liquid Phase Separated Coacervates.

Tau, an intrinsically disordered neuronal protein and polyampholyte with an overall positive charge, is a microtubule (MT) associated protein, which binds to anionic domains of MTs and suppresses their dynamic instability. Aberrant tau-MT interactions are implicated in Alzheimer's and other neurodegenerative diseases. Here, we studied the interactions between full length human protein tau and other negatively charged binding substrates, as revealed by differential-interference-contrast (DIC) and fluorescence microscopy. As a binding substrate, we chose anionic liposomes (ALs) containing either 1,2-dioleoyl-sn-glycero-3-phosphatidylserine (DOPS, -1e) or 1,2-dioleoyl-sn-glycero-3-phosphatidylglycerol (DOPG, -1e) mixed with zwitterionic 1,2dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) to mimic anionic plasma membranes of axons where tau resides. At low salt concentrations (0 to 10 mM KCl or NaCl) with minimal charge screening, reaction mixtures of tau and ALs resulted in the formation of distinct states of AL-tau complexes coexisting with liquid-liquid phase separated tau self-coacervates arising from the polyampholytic nature of tau containing cationic and anionic domains. AL-tau complexes exhibited distinct types of morphologies. This included, large ≈20-30 micron tau-decorated giant vesicles with additional smaller liposomes with bound tau attached to the giant vesicles, and tau-mediated finite-size assemblies of small liposomes. As the ionic strength of the solution was increased to near and above physiological salt concentrations for 1:1 electrolytes (≈150 mM), AL-tau complexes remained stable while tau self-coacervate droplets were found to dissolve indicative of breaking of (anionic/cationic) electrostatic bonds between tau chains due to increased charge screening. The findings are consistent with the hypothesis that distinct cationic domains of tau may interact with anionic lipid domains of the lumen facing monolayer of the axon plasma membrane suggesting the possibility of transient yet robust interactions at physiologically relevant ionic strengths.

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.

Clinical presentation of patients with lower limb spasticity undergoing routine treatment with botulinum toxin: baseline findings from an international observational study.

OBJECTIVE: Describe how people with lower limb spasticity present for treatment in routine clinical practice. METHODS: Prospective, observational study (Clinicaltrials.gov: NCT04050527) of ambulatory adult patients (≥ 18 years) with unilateral lower limb spasticity (able to take ≥ 5 steps with or without assistance) presenting for routine spasticity management, including treatment with abobotulinumtoxinA. RESULTS: The study population included 430 adults with lower limb spasticity. Despite their relatively young age (mean ± standard deviation 53.7 ± 13.9 years), only 20% of patients were employed. Most patients had an acquired brain injury due to cerebrovascular disease; 84.1% reported having concomitant upper limb spasticity. Using the Leg Activity Measure, most patients reported no or only mild difficulties in performing hygiene/positioning tasks, while 80.7% had at least mild difficulty with indoor ambulation and 90.5% had at least mild difficulty with walking outdoors. Sensory, communication and/or cognitive impairments were also common. At the first treatment cycle, 50.7% of patients set active function primary goals, including locomotion transferring or standing. CONCLUSION: These observations highlight the complexity of presentation that must be considered when setting treatment goals for lower limb spasticity and emphasize the types of impairment and activity (functional) limitations that treating teams may expect to encounter in their patients and should cover in their initial and follow-up assessments.

Improvement in quality of life of transfemoral amputees: Comparison between 2 types of transfemoral sockets and their influence on functionality and user comfort - A case report.

Among the components of lower limb prostheses, a perfectly adapted prosthetic socket is crucial to a successful rehabilitation process. Thus, developing a more comfortable socket could improve the quality of life for transfemoral (TF) amputees. The objective of this case report was to compare 2 TF sockets by evaluating the relationship between socket stiffness and user comfort and their influence on functionality to improve the quality of life of TF amputees. The participant received 2 different sockets: (A) flexible Flixt® socket; (B) conventional socket. He used each socket for 90 days, and after that was submitted to an evaluation at the Gait Laboratory (kinematic and dynamic analyses), completed the Prosthesis Evaluation Questionnaire, and performed Timed Up and Go test, 6-Minute March Test (6MWT), 10-Meter Walk Test, and Amputee Mobility Predictor test. After results were analyzed, the socket that obtained the best degree of satisfaction was assigned to the amputee participant. Combined measures showed that socket B does not considerably change the kinematic parameters neither dynamics parameters namely at stance phase. At Prosthesis Evaluation Questionnaire results, socket A had a better rating than socket B. The results of the Timed Up and Go test, 6MWT, 10-Meter Walk Test, and Amputee Mobility Predictor test obtained identical values, except for the 6MWT. This case report shows evidence of participant satisfaction improvement when using the flexible socket. The study also demonstrates that both sockets are quite effective.

A practical guide to botulinum neurotoxin treatment of shoulder spasticity 2: Injection techniques, outcome measurement scales, and case studies.

Introduction: Botulinum neurotoxin type A (BoNT-A) is a first-line treatment option for post-stroke spasticity, reducing pain and involuntary movements and helping to restore function. BoNT-A is frequently injected into the arm, the wrist, the hand, and/or the finger muscles but less often into the shoulder muscles, despite clinical trials demonstrating improvements in pain and function after shoulder BoNT-A injection. Methods: In part 2 of this two-part practical guide, we present an experts' consensus on the choice of outcome measurement scales and goal-setting recommendations for BoNT-A in the treatment of shoulder spasticity to increase awareness of shoulder muscle injection with BoNT-A, alongside the more commonly injected upper limb muscles. Expert consensus was obtained from five European experts with a cumulative experience of more than 100 years of BoNT-A use in post-stroke spasticity. Case studies are included as examples of approaches taken in the treatment of shoulder spasticity. Results: Although the velocity-dependent increase in muscle tone is often a focus of patient assessment, it is only one component of spasticity and should be assessed as part of a wider range of measurements. For outcome measurement following BoNT-A injection in shoulder muscles, shoulder-specific scales are recommended. Other scales to be considered include Pain Numerical Rating and/or global functioning, as well as the quality of life and global perception of benefit scores.Goal setting is an essential part of the multidisciplinary management process for spasticity; goals should be patient-centric, realistic, and achievable; functional-focused goal statements and a mixture of short- (3-6 month) and long-term (9-18 month) goals are recommended. These can be grouped into symptomatic, passive function, active function, involuntary movement, and global mobility.Clinical evaluation tools, goal setting, and outcome expectations for the multipattern treatment of shoulder spasticity with BoNT-A should be defined by the whole multidisciplinary team, ensuring patient and caregiver involvement. Discussion: These recommendations will be of benefit to clinicians who may not be experienced in evaluating and treating spastic shoulders.

A practical guide to botulinum neurotoxin treatment of shoulder spasticity 1: Anatomy, physiology, and goal setting.

Botulinum neurotoxin type A (BoNT-A) is a first-line treatment option for post-stroke spasticity, reducing pain and involuntary movements and helping to restore function. BoNT-A is frequently injected into the arm, wrist, hand and/or finger muscles, but less often into the shoulder muscles, despite clinical trials demonstrating improvements in pain and function after shoulder BoNT-A injection. In part 1 of this two-part practical guide, we present an experts' consensus on the use of BoNT-A injections in the multi-pattern treatment of shoulder spasticity to increase awareness of shoulder muscle injection with BoNT-A, alongside the more commonly injected upper limb muscles. Expert consensus was obtained from five European experts with a cumulative experience of more than 100 years of BoNT-A use in post-stroke spasticity. A patient-centered approach was proposed by the expert consensus: to identify which activities are limited by the spastic shoulder and consider treating the muscles that are involved in hindering those activities. Two patterns of shoulder spasticity were identified: for Pattern A (adduction, elevation, flexion and internal rotation of the shoulder), the expert panel recommended injecting the pectoralis major, teres major and subscapularis muscles; in most cases injecting only the pectoralis major and the teres major is sufficient for the first injection cycle; for Pattern B (abduction or adduction, extension and internal rotation of the shoulder), the panel recommended injecting the posterior part of the deltoid, the teres major and the latissimus dorsi in most cases. It is important to consider the local guidelines and product labels, as well as discussions within the multidisciplinary, multiprofessional team when deciding to inject shoulder muscles with BoNT-A. The choice of shoulder muscles for BoNT-A injection can be based on spastic pattern, but ideally should also firstly consider the functional limitation and patient expectations in order to establish better patient-centered treatment goals. These recommendations will be of benefit for clinicians who may not be experienced in evaluating and treating spastic shoulders.

Experiences of patients with poststroke spasticity throughout a botulinum toxin treatment cycle: Results from a prospective ethnographic study.

This study was conducted to capture the experience of patients with poststroke spasticity (PSS) throughout one botulinum neurotoxin A (BoNT-A) treatment cycle. The REBOT study (NCT03995524) was a prospective, observational ethnographic study conducted in France, Italy, the UK, and the USA. It combined a mixed-method ethnography (including semi-structured qualitative interviews within a week of a BoNT-A injection) with completion of a longitudinal quantitative patient-reported outcome questionnaire and sharing of video and images, both reported weekly over a 12-14-week period throughout the BoNT-A treatment cycle. The study recruited 30 adult patients with PSS who were receiving BoNT-A treatment. The most commonly used BoNT-A product was onabotulinumtoxinA (Botox®), which was administered to 21 patients (70%), whereas two patients (6.7%) received abobotulinumtoxinA (Dysport®) and seven patients (23.3%) did not specify the BoNT-A medication that they received. Patients reported a high, continuous burden of PSS, with spasms, sleeping difficulties, stiffness, and pain being the most commonly reported symptoms. In line with an observed waning effect of BoNT-A injections, spasticity symptoms initially were improved at Weeks 4-6 after injection but reemerged after 9-11 weeks. Treatment satisfaction levels decreased over the BoNT-A treatment cycle, as reflected by the worsening of symptoms and the need to self-medicate and consult a physician. The psychological impact of PSS was high. Patients acknowledged the benefits of BoNT-A treatment but wished for more individualized treatment plans with flexible dosing and injection intervals. Additionally, only 10% of patients reported that they had a trusting relationship with their physician and believed that their needs were considered by those managing their PSS. To our knowledge, this was the first ethnographic study in patients with PSS who were treated with BoNT-A. This ethnographic approach to patient surveys complements traditional research methods and allows improved identification of patients' unmet needs by capturing their weekly experience of treatment. The findings of this study confirm previous observations of the diminishing effectiveness of BoNT-A injections between treatment sessions, highlighting the need for agents with a longer duration of action and/or a more flexible treatment pattern that allows for more frequent injections.

Worldwide Survey of Clinician Practice on use of Adjunctive Therapies Following Botulinum Toxin Injection for Spasticity.

OBJECTIVE: Non-pharmacological adjunctive therapies can be used alongside botulinum toxin injection to enhance its efficacy. The objective of this global study was to determine the current practice and perception among clinicians of the use of adjunctive therapies after botulinum toxin injections for the treatment of limb spasticity. METHODS: A questionnaire with 22 questions on clinical practice demographics, self-reported use and clinician opinion on barriers to the use of complementary therapies, and priorities for future research was translated into 7 languages and distributed worldwide through national and international professional associations concerning (neuro)rehabilitation. RESULTS: A total of 527 clinicians from 52 countries responded to the survey. Most commonly used physical interventions were: active exercise programmes at home (81%), stretching programmes at home (81%), and splinting (70%), followed by active movement exercises (65%) and within 30 min of botulinum toxin injection and constraint induced movement therapy (63%). The main barriers reported by clinicians to provision of these interventions were clinicians' lack of time, limited financial resources, and lack of evidence. Future research should focus primarily on immediate active movement exercises and passive stretching. CONCLUSION: Worldwide, clinicians often recommend adjunctive therapies after a botulinum toxin injection to reduce spasticity. The most commonly used physical interventions among clinicians were active exercises at home, stretching at home, and splinting. Lack of evidence, time and financial constraints were identified as barriers to providing these interventions.

The spasticity-related quality of life 6-dimensions instrument in upper-limb spasticity: Part I Development and responsiveness.

OBJECTIVE: To describe the development of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D) and its sensitivity to clinical change (responsiveness). DESIGN: Multicentre, prospective, longitudinal cohort study at 8 UK sites (NCT03442660). PATIENTS: Adults (n = 104) undergoing focal treatment of upper limb spasticity. METHODS: No condition-specific health-related quality of life tool is available for upper-limb spasticity of any aetiology. The SQoL-6D was developed to fulfil this need, designed to complement the Upper Limb Spasticity Index (which incorporates the Goal Attainment Scaling evaluation of upper limb spasticity [GASeous] tool) with targeted standardised measures. The 6 dimensions of the SQoL-6D (score range 0-4) map onto common treatment goal areas identified in upper-limb spasticity studies. A Total score (0-100) provides overall spasticity-related health status. To assess responsiveness, the SQoL-6D, Global Assessment of Benefit scale and "GASeous" were administered at enrolment and 8 weeks. RESULTS: Significant differences in mean SQoL-6D Total score change and effect sizes across patients rating "some benefit" (0.51) and "great benefit" (0.88) supported responsiveness. CONCLUSION: The SQoL-6D is a promising new measure of health status in upper limb spasticity, that enables systematic assessment of the impact of this condition in relation to patients' priority treatment goals. A psychometric evaluation of SQoL-6D is presented separately.

The spasticity-related quality of life 6-dimensions instrument in upper-limb spasticity: Part II A first psychometric evaluation.

OBJECTIVE: Psychometric evaluation of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D). DESIGN: A clinimetric evaluation conducted in a multicentre, prospective, longitudinal cohort study at 8 UK sites. PATIENTS: Adult patients (n=104) undergoing focal treatment of upper-limb spasticity. METHODS: The SQoL-6D was administered in the clinic at enrolment and at 8 weeks, then 1-4 days later at home to assess test-retest reliability. RESULTS: The SQoL-6D demonstrated adequate construct validity and unidimensionality of the scale, allowing the calculation of a Total score. Cronbach's alpha (0.74) supported the internal consistency reliability, while the intraclass correlation coefficient supported test-retest reliability (0.82). Correlation coefficients with established instruments supported convergent validity, while significant differences between known-groups (of differing clinical severity) in SQoL-6D Total score confirmed its sensitivity to both cross-sectional and longitudinal differences. CONCLUSION: The SQoL-6D is a promising new measure to assess health status for patients with upper-limb spasticity of any aetiology. Further investigation and exploration of the allocation of weights to convert the SQoL-6D to a health-related quality of life utility index, are required.

Botulinum Toxin Services for Neurorehabiliation: Recommendations for Challenges and Opportunities during the COVID-19 Pandemic.

The COVID-19 pandemic severely impacted the function of medical facilities and rehabilitation services worldwide, including toxin services delivering Botulinum toxin treatments for neuromuscular conditions such as spasticity, dystonia, and sialorrhea. The aim of this paper is to understand how toxin services have dealt with the situation and what strategies have been adopted to continue services. The recommendations are based on a virtual round table held with toxin services experts from different European countries who shared their experiences and discussed the best practices. The challenges for toxin services were reviewed based on the experts' experiences and on relevant literature from 2020 and 2021. A set of recommendations and best practices were compiled, focusing firstly on guidance for clinical practice, including assessing patients' health and risk status and the urgency of their treatment. Secondly, it was discussed how patients on botulinum toxin therapy can be cared for and supported during the pandemic, and how modern technology and tele-medicine platforms can be generally used to optimize effectiveness and safety of toxin treatments. The technological advances prompted by the COVID-19 crisis can result in better and more modern patient care in the future.

Longitudinal goal attainment with integrated upper limb spasticity management including repeat injections of botulinum toxin A: Findings from the prospective, observational Upper Limb International Spasticity (ULIS-III) cohort study.

OBJECTIVE: To assess the longitudinal effects of integrated spasticity management incorporating repeated cycles of botulinum toxin A type A (BoNT-A) over 2 years. METHODS: The Upper Limb International Spasticity study was a prospective, observational, cohort study following adult patients over 2 years of integrated upper-limb spasticity management including repeat botulinum toxin (BoNT-A) treatment (any commercially-available product). RESULTS: A total of 1,004 participants from 14 countries were enrolled, of which 953 underwent ≥ 1 BoNT-A injection cycle (median 4 cycles) and had ≥ 1 goal attainment scaling assessment. Most participants (55.9-64.6% across cycles 1-6) saw a therapist after BoNT-A treatment; the most frequent therapy intervention was passive stretch (70.1-79.8% across cycles 1-6). Patients achieved their goals as expected over repeated cycles; mean cumulated goal attainment scaling T-score at 2 years was 49.5 (49.1, 49.9). Mean goal attainment scaling change scores of ≥ 10 were maintained across up to 7 cycles. Higher rates of goal achievement were seen for primary goals related to passive vs active function (86.6% vs 71.4% achievement). Standardized measures of spasticity, pain, involuntary movements, active and passive function improved significantly over the study. CONCLUSION: This large, international study provides evidence for benefit of repeated cycles of BoNT-A, over 2 years captured through person-centred goal attainment and standardized measures.

A practical guide to optimizing the benefits of post-stroke spasticity interventions with botulinum toxin A: An international group consensus.

This consensus paper is derived from a meeting of an international group of 19 neurological rehabilitation specialists with a combined experience of more than 250 years (range 4-25 years; mean 14.1 years) in treating post-stroke spasticity with botulinum toxin A. The group undertook critical assessments of some recurring practical challenges, not yet addressed in guidelines, through an exten-sive literature search. They then discussed the results in the light of their individual clinical experience and developed consensus statements to present to the wider community who treat such patients. The analysis provides a comprehensive overview of treatment with botulinum toxin A, including the use of adjunctive therapies, within a multidisciplinary context, and is aimed at practicing clinicians who treat patients with post-stroke spasticity and require further practical guidance on the use of botulinum toxin A. This paper does not replicate information published elsewhere, but instead aims to provide practical advice to help optimize the use of botulinum toxin A and maximize clinical outcomes. The recommendations for each topic are summarized in a series of statements. Where published high-quality evidence exists, the recommendations reflect this. However, where evidence is not yet conclusive, the group members issued statements and, in some cas-es, made recommendations based on their clinical experience.

Assessing the effectiveness of upper-limb spasticity management using a structured approach to goal-setting and outcome measurement: First cycle results from the ULIS-III Study.

OBJECTIVE: To describe the utility of a structured approach to assessing effectiveness following injection with botulinum toxin-A alongside physical therapies, within the first cycle of the Upper Limb International Spasticity-III (ULIS-III) study. METHODS: ULIS-III (registered at clinicaltrials.gov as NCT02454803) is a large international, observation-al, longitudinal study of adults treated for upper-limb spasticity. It introduces novel methods for the structured evaluation of person-centred goal attainment alongside targeted standardized outcome measures: the Upper limb Spasticity Index, and the Upper Limb Spasticity Therapy Recording Schedule. RESULTS: A total of 953/1,004 enrolled patients (95%) completed cycle 1. Mean overall goal attainment scaling (GAS) T scores were 49.8 (95% confidence interval 49.2-50.3; 67.1% of patients met their primary goal, with highest achievement rates for goals related to involuntary movement, (75.6%) and range of movement (74.4%). Standardized measures of spasticity, pain, involuntary movements, active and passive function, all improved significantly over the treatment cycle. Overall, 59.7% of patients saw a therapist following botulinum toxin-A injection. Interventions varied, as expected, with the set treatment goals. After controlling for concomitant therapies using the upper limb spasticity therapy recording schedule, significant differences in injection intervals (p < 0.001) were seen between the commercially-available botulinum toxin-A agents. CONCLUSION: The results of this study confirm the utility of the Upper Limb Spasticity Index and Upper Limb Spasticity Therapy Recording Schedule as a structured approach to capturing goal-setting, therapy inputs and outcomes assessment.

Velocity Determinants in Spastic Patients after Stroke-A Gait Analysis Study.

INTRODUCTION: Gait velocity in spastic patients after stroke is both a life quality and mortality predictor. However, the precise biomechanical events that impair a faster velocity in this population are not defined. This study goal is to find out which are the gait parameters associated with a higher velocity in stroke patients with spastic paresis. METHODS: The registries of a Gait analysis laboratory were retrospectively analyzed. The inclusion criteria were: trials of adult stroke patients with unilateral deficits. The exclusion criteria were: trials when patients used an external walking device, an orthosis, or support by a third person. Of the 116 initial patients, after the application of the exclusion criteria, 34 patients were included in the cohort, all with spatiotemporal, static and dynamic kinematic and dynamometric studies. RESULTS: There was a correlation of velocity with cadence, stride length of the paretic (P) limb, stride length, and time of the P and non-paretic (NP) limb, double support time, all the parameters related to hip extension during stance phase, knee flexion during swing phase, and parameters related to ankle plantarflexion during stance phase. CONCLUSIONS: The main gait analysis outcomes that have a correlation with speed are related to the formula velocity = step length × cadence or are related to stance phase events that allow the anterior projection of the body. The only swing phase outcome that has a correlation with speed is knee flexion. More studies are needed from gait analysis laboratories in order to point out the most relevant goals to achieve with gait training in spastic stroke patients.

Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity.

Background: Botulinum toxin-A (BoNT-A) injections are first-line treatment for adult spasticity. Prior patient surveys have reported that BoNT-A treatment improves quality of life but that symptoms usually recur before the next injection. We aimed to explore, in-depth, patient perceptions of the impact of spasticity and the waning of BoNT-A therapeutic effects. Methods: An internet-based survey was conducted through Carenity, an online patient community, from May to September 2019 in France, Germany, Italy, UK and USA. Eligible respondents were adult patients with spasticity due to stroke, traumatic brain injury (TBI) or spinal cord injury (SCI) who had ≥2 previous BoNT-A injections. Results: Two hundred and ten respondents (mean 47.2 years) met screening criteria and had their responses analyzed. Overall, 43% of respondents had spasticity due to stroke, 30% due to TBI and 27% due to SCI. The mean [95% CI] injection frequency for spasticity management was 3.6 [3.4-3.7] injections/year. Respondents described the time profile of their response to BoNT-A. The mean reported onset of therapeutic effect was 12.9 [12.1-13.7] days and the mean time to peak effect was 5.0 [4.7-5.4] weeks. Symptom re-emergence between injections was common (83%); the time from injection to symptom re-emergence was 89.4 [86.3-92.4] days. Muscle spasms usually re-emerge first (64%), followed by muscle stiffness or rigidity (40%), and limb pain (20%). Over half (52%) of respondents said they had lost their self-confidence, 46% experienced depression and 41% experienced a lack of sleep due to their spasticity symptoms in the past 12 months. Following a report of symptom re-emergence, the most common management approaches were to add adjunctive treatments (36%), increase the BoNT-A dose (28%), and wait for the next injection (26%). Seventy two percentage of respondents said they would like a longer lasting BoNT-A treatment. Conclusions: Patients with spasticity can expect a characteristic profile of BoNT-A effects, namely time lag to onset and peak effect followed by a gradual decline in the symptomatic benefits. Symptom re-emergence is common and has significant impact on quality of life. Greater patient/clinician awareness of this therapeutic profile should lead to better level of overall satisfaction with treatment, informed therapeutic discussions and treatment schedule planning.

Corrigendum: Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity.

[This corrects the article DOI: 10.3389/fneur.2020.00388.].

OrthoRehab: Development of a New Methodology for the Comparison Study Between Different Types of Ankle-Foot Orthoses in Foot Dysfunction.

Foot dysfunction is one of the most likely consequences of rheumatoid arthritis and stroke. It is characterized by severe changes in the gait pattern due to a significant increase in the plantar flexion. Some of these dysfunctions can be compensated by using an ankle-foot orthosis. However, the clinical decision about which orthosis best suits the patient creates a real problem for physicians/therapists. Purpose: The main goal of this paper is to present a quantitative support tool that can assist the physicians/therapists in deciding which orthosis is most suitable for each subject. Methodology: In order to achieve such goal, a platform named OrthoRehab was developed, and it was tested in three conditions: without any orthosis and with two different ankle-foot orthoses. The data were acquired in the Gait Laboratory of Rehabilitation Medicine Center of Alcoitão using a VICON NEXUS 1.8.5® motion capture system that allows the capturing of kinematic and kinetic data. Results: The results reveal that OrthoRehab is a user-friendly, easy to apply tool that analyzes very relevant data for the clinical staff. Conclusion: The developed decision support tool, OrthoRehab, offers a quantitative analysis and provides insight to which orthosis achieves the best performance in comparison with the patient's gait pattern with no orthosis.

Analysis of a 15-years' experience in including shoulder muscles, when treating upper-limb spasticity post-stroke with botulinum toxin type A.

Background Botulinum toxin type-A (BoNTA) is a recognized treatment for upper limb spasticity (ULS) after stroke, but there aren't many studies analyzing its effect in shoulder muscles. Objective To evaluate the efficacy of BoNTA injections for ULS, when shoulder muscles are included. Methods A cross-sectional study. Data from clinical forms of outpatients, treated at a Rehabilitation Center (2001-2016). Analyzes: goals of treatment; demographic characteristics/goal; treatment success, using Goal Attainment Scaling. Results Eighty-six stroke-patients, submitted to 547 BoNTA treatment sessions. The most injected shoulder muscles were subscapularis (SC) 35%, pectoralis major (PM) 31%, deltoideus 14%. The most selected goals for treatment were: involuntary movements (IM) 33%, pain/discomfort (PD) 26%, and mobility (MOB) 18%. Patients achieved or overachieved the IM goal in 76%, PD in 78%, and MOB in 79%. Patients with IM goal were younger (p < 0.01), than those setting other goal types; PD patients, were older (p < 0.019), treated half a year earlier (p < 0.01), and had more spasticity (MAS ≠ 0.15); MOB patients were younger (p = 0.04) and less spastic (MAS ≠ 0.12). Achieving PD goal impacted positively in improving MOB (p = 0.042) and passive function (p = 0.018). Conclusion When treating ULS, including shoulder muscles, the most frequent goals were IM, PD e MOB. The most injected muscles were SC and PM. The treatment was successful in a large percentage of cases. Achieving the PD goal was associated with greater success at other goals of treatment. BoNTA demonstrated a positive effect in controlling symptoms and improving function.