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Background: Spastic movement disorder (SMD) develops in up to 43% of cases as a sequela of stroke. In the event of a functionally relevant or daily life impairing SMD or to avoid an impending complication, the medicinal treatment of a focal, multifocal and segmental increase in muscle tone with botulinum neurotoxin A (BoNT-A) is recommended; however, treatment data reveal a lack of guideline-conform treatment with BoNT‑A in Germany., Objective: The aim of the reported expert meeting was to discuss solutions to the incorrect treatment and undertreatment of patients with SMD and to formulate consensus recommendations to improve the care situation., Methods: At a consensus meeting held in April 2022, eight experts from the fields of neurology, physical medicine and rehabilitation discussed the causes for the incorrect treatment and undertreatment and formulated consensus solution approaches., Results: Possible reasons for the current incorrect treatment and undertreatment in SMD management in Germany include insufficient awareness of SMD among physicians, a lack of treatment capacities, a lack of information transfer in discharge management as well as staff shortages in the specialized inpatient and outpatient SMD treatment centers. The committee therefore recommended a patient pathway in which affected patients with SMD are provided with correctly implemented BoNT‑A treatment in combination with physical measures., Conclusion: The recommended treatment pathway for use in stroke patients is intended to close gaps in care and thus ensure guideline-conform treatment of post-stroke SMD., (© 2023. The Author(s).)

Post-stroke spastic movement disorder (PS-SMD) is one of the main causes of severe disability in the chronic phase after stroke. The prevalence of SMD goes up with time after stroke to more than 28% in the chronic phase., Its secondary complications such as contracture, abnormal postures and/or movement patterns, spasticity-associated pain also increase with time after stroke when physical and medical management of PS-SMD have been delayed in the early stroke phase. It has been published by several controlled studies that the earlier physical and medical measures, such as botulinum toxin type A (BoNT-A) therapy are included in rehabilitative strategies for the SMD, the fewer secondary complications, especially soft tissue contractures and pain occurred. Several studies showed that goal-orientated management of PS-SMD including BoNT-A therapy, applied within a few weeks and three months - in the early subacute phase after stroke onset - prevented or reduced the development of severe or disabling SMD and its secondary complications, more effective than late application of BoNT-A therapy - in the chronic phase after stroke. In multiple prospective cohort studies, various predictors and predictive approaches for detection of patients on risk to development PS-SMD were found. Based on that information and the controlled studies that showed reduction in PS-SMD complications following early treatment with BoNT-A nowadays, early treatment of PS-SMD in the early subacute phase following stroke is recommended to avoid or reduce the development of post-stroke disability and to improve the outcome of rehabilitation. In this review, we discuss the optimal timing to apply BoNT-A therapy in patients with already present as well as those at high risk of severe PS-SMD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jörg Wissel was speaker and advisory board member with honorarium for Allergan, Ipsen, Merz, and Medtronic. Anatol Kivi was speaker and advisory board member with honorarium for Allergan and Merz. Songjin Ri was speaker and advisory board member with honorarium for Allergan., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This analysis pooled pain severity data from four phase 3 and 4 studies of incobotulinumtoxinA (incoBoNT-A) for the treatment of cervical dystonia (CD) in adults. CD-related pain severity was assessed at baseline, each injection visit, and 4 weeks after each injection of incoBoNT-A using the Toronto Western Spasmodic Torticollis Rating Scale pain severity subscale or a pain visual analog scale. Both were analyzed using a score range of 0-10 and pain was categorized as mild, moderate, or severe. Data for 678 patients with pain at baseline were assessed and sensitivity analyses evaluated pain responses in the subgroup not taking concomitant pain medication ( n = 384 at baseline). At Week 4 after the first injection, there was a mean change of -1.25 (standard deviation 2.04) points from baseline pain severity ( p < 0.0001), with 48.1% showing ≥ 30% pain reduction from baseline, 34.4% showing ≥50% pain reduction from baseline, and 10.3% becoming pain free. Pain responses were sustained over five injection cycles with a trend to incremental improvements with each successive cycle. Pain responses in the subgroup not taking concomitant pain medication demonstrated the lack of confounding effects of pain medications. These results confirmed the pain relief benefits of long-term treatment with incoBoNT-A.

Introduction: Post-stroke spastic movement disorder (PS-SMD) appears up to 20% in the first week following stroke and 40% in the chronic phase. It may create major hurdles to overcome in early stroke rehabilitation and as one relevant factor that reduces quality of life to a major degree in the chronic phase., Areas Covered: In this review, we discuss predictors,early identification, clinical assessments, goal setting, and management in multiprofessional team, including Botulinum neurotoxin A (BoNT-A) injection for early and chronic management of PS-SMD., Expert Opinion: The earlier PS-SMD is recognized and managed, the better the outcome will be. The comprehensive management in the subacute or chronic phase of PS-SMD with BoNT-A injections requires detailed assessment, patient-centered goal setting, technical-guided injection, effective dosing of BoNT-A per site, muscle, and session and timed adjunctive treatment, delivered in a multi-professional team approach in conjunction with physical treatment. Evidence-based data showed BoNT-A injections are safe and effective in managing focal, multifocal, segmental PS-SMD and its complications. If indicated, BoNT-A therapy should be accompanied with adjunctive treatment in adequate time slots. BoNT-A could be added to oral, intrathecal, and surgical treatment in severe multisegmental or generalized PS-SMD to reach patient/caregiver's goals, especially in chronic PS-SMD.

Some studies have shown that incobotulinumtoxinA reduces spasticity-associated pain, but further evidence is needed. This exploratory analysis pooled pain-relief data from six Phase 2 or 3 studies of incobotulinumtoxinA (four placebo-controlled studies) for treating upper limb spasticity in adults. Spasticity-associated pain was assessed at baseline and 4 weeks post incobotulinumtoxinA injection using the disability assessment scale (DAS) for pain. Only data for patients with pain at baseline were analysed. Overall, 544 (incobotulinumtoxinA, N = 415; placebo, N = 129) of 937 patients (58.1%) experienced pain at baseline. At Week 4, a significantly greater proportion of incobotulinumtoxinA- (52.1%) than placebo-treated patients (28.7%; Chi-square p < 0.0001) showed a response (≥1-point improvement in DAS pain score). In logistic regression analysis, incobotulinumtoxinA-treated patients were 2.6 times more likely to achieve this endpoint than placebo-treated patients. A significant difference between incobotulinumtoxinA and placebo was observed regardless of baseline pain severity. Additionally, 27.1% of incobotulinumtoxinA- versus 12.4% of placebo-treated patients reported complete pain relief at Week 4 ( p = 0.0006). Pain relief increased with multiple injection cycles. To achieve patient-centred care, pain relief may be considered a treatment goal in adults with spasticity-associated pain regardless of pain severity. This study contributes to understanding the benefits of incobotulinumtoxinA in treating limb spasticity-associated pain.

Background: Lower-limb spasticity can impair ambulation and gait, impacting quality of life., Objectives: This ancillary analysis of the TOWER study (NCT01603459) assessed the efficacy of incobotulinumtoxinA for lower-limb post-stroke spasticity including pes equinovarus., Methods: Participants received escalating incobotulinumtoxinA doses (400-800U) across 3 injection cycles. Changes were compared for those treated in the lower limb (with/without upper-limb treatment) or the upper limb only or for participants treated or untreated for pes equinovarus. Outcome measures were those used in the seminal study: resistance to passive movement scale (REPAS), Ashworth Scale (AS), functional ambulation and lower-limb goal attainment., Results: Among 132/155 (85%) participants with post-stroke spasticity, in cycles 1, 2 and 3, 99, 119 and 121 participants received lower-limb treatment with mean (SD) total limb incobotulinumtoxinA doses of 189.2 (99.2), 257.1 (115.0) and 321.3 (129.2) U, respectively. Of these, 80, 105 and 107, respectively, were treated for pes equinovarus. The mean (SD) improvement in REPAS lower-limb score was greater with treatment in the lower limb versus the upper limb only: -1.6 (2.1) versus-0.4 (1.4); -1.9 (1.9) versus -0.6 (1.6); -2.2 (2.2) versus -1.0 (0.0) (P=0.0005, P=0.0133 and P=0.3581; analysis of covariance [ANCOVA], between-group differences) in cycles 1, 2 and 3, respectively. For all cycles, the mean improvement in ankle joint AS score from injection to 4 weeks post-treatment was greater for participants treated versus not treated for pes equinovarus, with a significant between-group difference in cycle 1 (P=0.0099; ANCOVA). At the end of cycle 3, 42% of participants walked independently and 63% achieved 2 of 2 lower-limb treatment goals (baseline 23% and 34%, respectively)., Conclusions: This study supports the efficacy of incobotulinumtoxinA for treatment of pes equinovarus and other patterns of lower-limb post-stroke spasticity., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: The Titration study in lOWer and uppER-limb spasticity (TOWER) study (NCT01603459), evaluated incobotulinumtoxinA for upper- and lower-limb spasticity. This post hoc analysis assessed shoulder spasticity in patients who received injections into the shoulder., Methods: Subjects received 3 injection cycles with escalating incobotulinumtoxinA doses on the same side (400, 600, 600-800 U; ≤ 600 U per limb including optional shoulder dose, planned range 100-250 U). Joint function was assessed with the Ashworth Scale shoulder sumscore (AS-SSS) in subjects treated in the shoulder vs those who were not. Safety was assessed in subjects treated in the shoulder, and in those who had upper-limb treatment without shoulder treatment., Results: The proportion of subjects receiving shoulder treatment increased with escalating dose at each cycle (n = 84/140 (60.0%) by cycle 3; mean (standard deviation (SD)) shoulder dose 118.4 U (SD 60.2)). From baseline to 4-weeks post-injection, mean AS-SSS improved by -1.1 (SD 1.9), -1.7 (SD 1.8) and -1.7 (1.8) in cycles 1, 2 and 3, respectively, in subjects treated in the shoulder, and -0.5 (SD 1.3), -0.8 (SD 1.6) and -0.9 (SD 1.4) in subjects who were not. A significant dose effect on AS-SSS was observed in cycle 3 (p = 0.0081). No unexpected safety concerns were reported., Conclusion: The results demonstrate an improvement in shoulder spasticity and safety following incobotulinumtoxinA treatment.

Background: We evaluated quality of life among subjects with upper- and lower-limb spasticity who received escalating doses of incobotulinumtoxinA (total body doses up to 800 U) in the prospective, single-arm, dose-titration TOWER study., Methods: In this exploratory trial, subjects (N = 155; 18-80 years of age) with upper- and lower-limb spasticity due to cerebral causes who were deemed to require total body doses of up to 800 U incobotulinumtoxinA received three consecutive injection cycles of incobotulinumtoxinA (400, 600, and up to 800 U), each with 12 to 16 weeks' follow-up. QoL was assessed using the EuroQol 5-dimensions questionnaire, three-level (EQ-5D), before and 4 weeks post-injection in each injection cycle and at the end of injection cycle 3., Results: The mean EQ-5D visual analog scale scores of 155 participants continuously improved from study baseline to 4 weeks post-injection in all injection cycles (mean [standard deviation] change 6.7 [14.1], 9.6 [16.3], and 8.6 [17.0] for injection cycles 1, 2, and 3, respectively; p < 0.0001 for all, paired sample t-test). In general, among those with a change in the EQ-5D rating of their condition, the proportion of subjects with 'improvement' was greater than that with 'worsening' for individual EQ-5D dimensions across all injection cycles. At the end of injection cycle 3, the proportion of subjects rating their condition as 'normal' increased from study baseline for all dimensions, and there was a ≥ 46% reduction in the proportion of subjects with a rating of 'severe impairment'., Conclusion: These preliminary results suggest that escalating incobotulinumtoxinA doses up to 800 U are associated with improvement in quality of life ratings in subjects with multifocal upper- and lower-limb spasticity, and form a basis for future comparator studies., Trial Registration: ClinicalTrials.gov, NCT01603459. Date of registration: May 22, 2012.

Botulinum neurotoxin (BoNT) is an effective, well-tolerated, and well-established option for the treatment of dystonic and spastic movement disorders. However, a single approach does not suit all patients, even within one disease indication. The degree of flexibility in treatment protocols is determined by individual product licenses, which often lag behind real-world clinical experience. A number of patient/practitioner surveys conducted recently have highlighted a desire for greater flexibility than that currently approved, both in BoNT doses and in the intervals between consecutive doses. New evidence arising from research conducted during the last few years has opened new avenues for tailoring BoNT treatment to patients' needs. Data suggest that escalating incobotulinumtoxinA doses enables treatment of a greater number of spasticity patterns than current dose limitations allow, without compromising safety or tolerability. Similarly, in patients with cervical dystonia (CD), repeated injections of incobotulinumtoxinA at intervals as early as 6 weeks after a previous treatment, based on individual patient need, were effective and well tolerated. Here, the BoNT doses and dosing intervals currently indicated in the USA and European Union are reviewed, together with the use of BoNT for the treatment of spasticity, CD, and blepharospasm. Opportunities for tailored BoNT therapy are also discussed., (Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate safety (primary objective) and efficacy of increasing doses (400 U up to 800 U) of incobotulinumtoxinA (Xeomin, Merz Pharmaceuticals GmbH) for patients with limb spasticity., Methods: In this prospective, single-arm, dose-titration study (NCT01603459), patients (18-80 years) with spasticity due to cerebral causes, who were clinically deemed to require total doses of 800 U incobotulinumtoxinA, received 3 consecutive injection cycles (ICs) with 400 U, 600 U, and 600-800 U incobotulinumtoxinA, respectively, each followed by 12-16 weeks' observation. Outcomes included adverse events (AEs), antibody testing, Resistance to Passive Movement Scale (REPAS; based on the Ashworth Scale), and Goal Attainment Scale., Results: In total, 155 patients were enrolled. IncobotulinumtoxinA dose escalation did not lead to an increased incidence of treatment-related AEs (IC1: 4.5%; IC2: 5.3%; IC3: 2.9%). No treatment-related serious AEs occurred. The most frequent AEs overall were falls (7.7%), nasopharyngitis, arthralgia, and diarrhea (6.5% each). Five patients (3.2%) discontinued due to AEs. No patient developed secondary nonresponse due to neutralizing antibodies. Mean (SD) REPAS score improvements from each injection to 4 weeks postinjection increased throughout the study (IC1: -4.6 [3.9]; IC2: -5.9 [4.2]; IC3: -7.1 [4.8]; p < 0.0001 for all). The proportion of patients achieving ≥3 (of 4) treatment goals also increased (IC1: 25.2%; IC2: 50.7%; IC3: 68.6%)., Conclusion: Escalating incobotulinumtoxinA doses (400 U up to 800 U) did not compromise safety or tolerability, enabled treatment in a greater number of muscles/spasticity patterns, and was associated with increased treatment efficacy, improved muscle tone, and goal attainment., Clinicaltrialsgov Identifier: NCT01603459., Classification of Evidence: This study provides Class IV evidence that, for patients with limb spasticity, escalating incobotulinumtoxinA doses (400 U up to 800 U) increases treatment efficacy without compromising safety or tolerability., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To characterize patient and physician satisfaction with current standard-of-care botulinum toxin treatment regimens for symptom control in patients with post-stroke spasticity using structured interviews with patients and physicians., Research Design and Methods: Two cross-sectional surveys were conducted in Canada, France, Germany, and the US. The patient survey included patients with post-stroke spasticity who had undergone at least two botulinum toxin A injection cycles. Information on patients' current and prior botulinum toxin treatment cycles and quality of life was collected. The physician survey included physicians treating post-stroke spasticity with botulinum toxins and collected information regarding physician satisfaction with botulinum toxin treatment for post-stroke spasticity., Results: Of 79 participating patients with post-stroke spasticity, 61 (77%) received treatment with onabotulinumtoxinA, 15 (19%) with abobotulinumtoxinA, and three (4%) with incobotulinumtoxinA. Overall, 40.5% of patients were very satisfied, 48.1% were somewhat satisfied, and 11.4% were not at all satisfied with botulinum toxin treatment. Patient satisfaction was lowest just before injection and highest at the time of peak effect. The mean injection interval was 13.7 (SD = 3.5) weeks; however, 43.4% of patients expressed a preference for intervals of ≤ 10 weeks. Most of the 105 participating physicians' were moderately (57.7%) or very (36.5%) satisfied with botulinum toxin treatment. However, physicians estimated that 16.2% of their patients with post-stroke spasticity could benefit from shorter injection intervals, and that 24.6% of patients could benefit from higher doses than those permitted by current country directives., Study Limitations: Patients' responses were based on subjective recollections and physicians' responses were based on general impressions., Conclusions: These surveys indicate that patients' and physicians' satisfaction with botulinum toxin therapy for post-stroke spasticity is overall very good. However, patients' satisfaction over the treatment cycle varied with onset, peak, and trough of treatment effects and patients and physicians expressed a need for treatment individualization.

Objective: Evaluate changes in active and passive function with onabotulinumtoxinA + standard of care within goal-oriented rehabilitation programmes in adults with focal post-stroke spasticity., Methods: Prospective, 24-week double-blind study with an open-label extension. Subjects were randomized to onabotulinumtoxinA + standard of care or placebo + standard of care, at baseline and at 12 weeks, if judged appropriate, with follow-up to 52 weeks. The primary endpoint was the number of patients achieving their principal active functional goal at 24 weeks (or 10 weeks after an optional second injection). Secondary endpoints included achievement of a different active or a passive goal at this timepoint., Results: The intent-to-treat population comprised 273 patients. The proportion of patients achieving their principal active functional goal and secondary active functional goal with onabotulinumtoxinA + standard of care was not statistically different from placebo + standard of care. Significantly more patients achieved their secondary passive goal with onabotulinumtoxinA + standard of care (60.0%) vs. placebo + standard of care (38.6%) (odds ratio, 2.46; 95% confidence interval, 1.18-5.14) as well as higher Goal Attainment Scaling levels for upper limb and ankle flexor subgroups., Conclusions: Addition of onabotulinumtoxinA to standard of care as part of goal-oriented rehabilitation in post-stroke spasticity patients significantly increased passive goal achievement and was associated with higher levels of active function.

A significant percentage of patients suffering from a stroke involving motor-relevant central nervous system regions will develop a spastic movement disorder. Hyperactivity of different muscle combinations forces the limbs affected into abnormal postures or movement patterns. As muscular hyperactivity can effectively and safely be treated with botulinum toxin type A (BoNT-A), we present a classification of spastic arm movement patterns to support BoNT-A therapy of arm spasticity. A few characteristic patterns can be distinguished that may be relevant for BoNT-A treatment. On the basis of a differentiated posture and arm movement analysis, five characteristic arm spasticity patterns (ASP I-V) were defined with respect to the position of the shoulder, elbow, forearm, and wrist joints. These patterns were verified using data from a worldwide noninterventional Upper Limb International Survey. By clinical observation, spastic arm postures in 94% of 665 poststroke patients could be assigned to one of these five ASPs. The most frequent pattern of arm spasticity was ASP III (41.8%) with internal rotation and adduction of the shoulder and flexion at the elbow coupled with a neutral positioning of the forearm and wrist, not the typical Wernicke-Mann position. These five different arm position patterns (ASP I-V) form the foundation of a common terminology and facilitate quick and understandable exchange of information with other physicians. Furthermore, utilization of these patterns may improve the dosing, goal setting, and outcome of the BoNT-A treatment of arm spasticity.

A standardization of injection procedures for the various botulinum toxin (BoNT) indications has not been achieved to date. One established option to guide the therapist's needle is sonography guidance. It provides real-time visualization of the injection process, which is quick, allows perfect precision, and the procedure as such is painless. To demonstrate these qualities, we have recorded six split-screen video segments that show the handling of the probe and the needle during BoNT injections concurrently with the respective cross-sectional sonography recordings. The video sequences show differentiation of the pollicis longus muscle and individual finger flexor fascicles, needle tracking, and real-time sonography-guided injection of the gastrocnemius, rectus femoris, and iliopsoas muscles. We hope this short presentation will help to encourage a more widespread use of the technique as well as further research on sonography guidance for precise delivery of BoNT injections to various target muscles.

A group of clinicians from across Europe experienced in the use of botulinum toxin type A for the treatment of spasticity following acquired brain injury gathered to develop a consensus statement on best practice in managing adults with spasticity. This consensus table summarizes the current published data, which was collated following extensive literature searches, their assessment for level of evidence and discussion among the whole group. Published information is supplemented by expert opinion based on clinical experience from 16 European countries, involving 28 clinicians, who treat an average of approximately 200 patients annually, representing many thousand spasticity treatments with botulinum toxin per year.

Hereditary spastic paraplegia (HSP) is characterized by lower extremity spasticity. Symptomatic therapy generally includes physical therapy and oral antispastic agents, in selected cases intrathecal baclofen. Because of the positive results in other treatments of spasticity, the use of botulinum neurotoxin type A (BoNT-A) might also be considered for patients with HSP. We report the effect of BoNT-A injections in 19 unselected patients with HSP treated by the members of the German Spasticity Education Group. In 17 patients, the modified Ashworth scale had improved by one point. In one patient, it improved by three points. Most of the patients reported reduction of spasticity. BoNT-A injections were continued in 11 of 19 patients (57.9%). All of the patients with continued injections had a good or very good global subjective improvement. Patients with less pronounced spasticity and patients with accompanying physical therapy tended to exhibit a better effect. Only four patients reported adverse effects which were increased weakness in three patients and pain in one patient. BoNT-A injections appear to reduce spasticity effectively and safely, especially in patients with mild to moderate spasticity. The preliminary results of our case series should encourage larger studies of BoNT-A injections in HSP., (2007 Movement Disorder Society)

Adductor spasticity in children with cerebral palsy (CP) impairs motor function and development. In a placebo-controlled, double-blind, randomized multicentre study, we evaluated the effects of botulinum toxin A(BTX-A) in 61 children (37 males, 24 females; mean age 6 years 1 month [SD 3y 1mo]) with CP (leg-dominated tetraparesis, n=39; tetraparesis, n=22; GMFCS level I, n=3; II, n=6; III, n=17; IV, n=29; V, n=6). Four weeks after treatment, a significant superiority of BTX-A was observed in the primary outcome measure (knee-knee distance 'fast catch', p=0.002), the Ashworth scale (p=0.001), and the Goal Attainment Scale (p=0.037).