Multimodal therapy and use of adjunctive therapies to BoNT-A in spasticity management: defining terminology to help enhance spasticity treatment.

Spasticity management should be provided within the context of a comprehensive person-centered rehabilitation program. Furthermore, active goal setting for specific spasticity interventions is also important, with a well-established "more is better" approach. It is critical to consider adjunctive therapy and multimodal approaches if patients are not attaining their treatment goals. Often used interchangeably, there may be confusion between the terms adjunctive and multimodal therapy. Yet it is imperative to understand the differences between these approaches to achieve treatment goals in spasticity management. Addition of a secondary pharmacologic or non-pharmacologic treatment to optimize the efficacy of the initial modality, such as adding electrical stimulation or casting to BoNT-A, is considered an adjunctive therapy. Adjunctive therapy is time-specific and requires the added therapy be initiated within a specific period to enhance the primary treatment; usually within 2 weeks. Multimodal therapy is an integrated, patient-centric program of pharmacologic and non-pharmacologic strategies utilized in a concurrent/integrated or sequential manner to enhance the overall treatment effect across a variety of spasticity-associated impairments (e.g., neural and non-neural components). Moreover, within a multimodal approach, adjunctive therapy can be used to help enhance the treatment effect of one specific modality. The objectives of this paper are to clarify the differences between adjunctive and multimodal therapies, provide a brief evidence-based review of such approaches, and highlight clinical insights on selecting multimodal and adjunctive therapies in spasticity management.

Botulinum Neurotoxin-A Injection in Adult Cervical Dystonia and Spastic Paresis: Results From the INPUT (INjection Practice, Usage and Training) Survey.

Botulinum toxin-A (BoNT-A) is an effective treatment for cervical dystonia (CD) and spastic paresis (SP), but it requires in-depth knowledge of anatomy and injection techniques. The Ixcellence Network® is an educational programme to provide neurology, neuropaediatrics, and physical medicine and rehabilitation (PMR) specialists with access to best clinical practices and innovations regarding SP and CD management with BoNT-A. To assess the benefits of such educational programmes and identify unmet needs, a multidisciplinary scientific committee designed INPUT (INjection Practice, Usage & Training), an international multicentric survey describing training and practices among this trained and experienced population. A self-completed questionnaire was sent online to 553 trainees and 14 trainers from the Ixcellence Network®. Among the 131 respondents, 92% specialized in PMR (48%) or neurology (44%), with a mean experience of 15.5 years in their clinical fields and 10.9 years of BoNT-A injection. Most of them (98%) reported having received training before performing their first BoNT-A injection and attending specific courses on how to perform it without any instrumental guidance (76%), and with ultrasound (73%), electrical stimulation (44%) or electromyography (41%). In terms of practices, 92% of respondents reported using at least one guidance technique while injecting, with ultrasound being the most used technique (48%). Attending specific courses was significantly associated with greater self-confidence and use, e.g. for injection with ultrasound, mean self-confidence, on a scale from 1 (not confident) to 10 (fully confident), was 7.9 for trained respondents (vs 4.0 for untrained respondents, p < 0.001) of whom 70% stated that they used this technique regularly or systematically (vs. 11% of untrained healthcare professionals (HCPs), p < 0.0001). Moreover, 84% of respondents reported having trained colleagues, residents or fellows through theoretical (70%) or practical teaching in individuals (80%) or in small groups (65%). Overall, 86% of respondents reported a notable increase over the past 5 years of the number of patients treated with BoNT-A. INPUT is the first international survey describing training and practices in SP and CD management of physicians who attended a dedicated educational programme. The results highlighted the importance of training for self-confidence, and the use of specific techniques and new approaches.

Efficacy and Safety of AbobotulinumtoxinA for the Treatment of Hemiparesis in Adults with Lower Limb Spasticity Previously Treated With Other Botulinum Toxins: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA. DESIGN: Secondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study. SETTING: Fifty-two centers (11 countries). PATIENTS: Adults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb. MAIN OUTCOME MEASUREMENTS: Muscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented. RESULTS: Of 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA. CONCLUSIONS: Patients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT-A products.

Management of Spastic Paresis and Cervical Dystonia: Access to Therapeutic Innovations Through an International Program of Practical Courses.

PURPOSE: Our purpose was to determine satisfaction and confidence of the Ixcellence Network training program on health care practitioners using botulinum toxin A (BoNT-A) for neurologic disorders, including spastic paresis and cervical dystonia. METHODS: The Ixcellence Network training program was designed by a scientific committee of 6 experts and then tested at centers in Europe, and Latin America. The training, provided by 16 experienced neurologists and rehabilitation specialists, consisted of theoretic and practical sessions that covered the different stages of the patient's journey from diagnosis to tailored treatment and rehabilitation. Trainees' feedback and the impact on participants' practice were evaluated by 2 individual questionnaires, at the end of the session (T0) and at 6 months (T6). Trainers' feedback was also collected through an individual questionnaire. FINDINGS: Between September 2012 and December 2017, 728 trained physicians participated in training programs with 48%, 23%, and 29% of attendees participating in training sessions dedicated to adult spastic paresis, child spastic paresis, and cervical dystonia, respectively. At T0, 93% of attendees thought that they had been given new information and 90% thought that the training would change their daily practice. This was confirmed at T6 by 93% of respondents. Trainees were highly satisfied with the program, in particular with the practical sessions. Trainers expectations were met for attendees' level of expertise, motivation, language, and participation. IMPLICATIONS: In this descriptive study, we show that the Ixcellence Network program represents a new educational approach to promote consistency in care practices and dissemination of expertise on the use of BoNT-A for neurologic disorders.

Ixcellence Network®: an international educational network to improve current practice in the management of cervical dystonia or spastic paresis by botulinum toxin injection.

Botulinum toxin is a well-established treatment for a number of conditions involving muscle hyperactivity, such as focal dystonia and spastic paresis. However, current injection practice is not standardized and there is a clear need for structured training. An international group of experts in the management of patients with cervical dystonia (CD) and spastic paresis created a steering committee (SC). For each therapeutic area, the SC developed a core slide set on best practice, based on the literature. International sites of expertise were identified for training and courses were designed to include lectures and casebased learning. Where possible, courses received accreditation from the European Union of Medical Specialists (UEMS). Each course was peer reviewed by the SC, the UEMS accreditation board and the attendees themselves (through evaluation questionnaires). Attendees' feedback was shared with the SC and the trainers to tailor future training sessions. From the program launch in 2012 to December 2014, 328 physicians from 34 countries were trained in a total of 58 courses; 67% of the courses focused on spastic paresis and 33% on CD. Of the 225 (69%) physicians who completed feedback forms, 95% rated their course as 'above average/excellent' in meeting the preset learning objectives. Most (90%) physicians declared that attending a course would lead them to change their practice. The development of the 'Ixcellence Network' for continuous medical education in the fields of spastic paresis and CD has provided a novel and interactive way of training physicians with previous experience in botulinum toxin injection.

Botulinum Neurotoxin Type A in Neurology: Update.

This paper reviews the current and most neurological (central nervous system, CNS) uses of the botulinum neurotoxin type A. The effect of these toxins at neuromuscular junction lends themselves to neurological diseases of muscle overactivity, particularly abnormalities of muscle control. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical purpose, and they have proved to be safe and effective for the treatment of dystonia, spasticity, headache, and other CNS disorders in which muscle hyperactivity gives rise to symptoms. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neuro-transmitters involved in pain regulation. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to the dose, allowing individualized treatment of patients and disorders. It may also prove to be useful in the control of autonomic dysfunction and sialorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy.