Botulinum Neurotoxin Type A Treatment Research Articles

Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions.

Botulinum neurotoxin type-A (BoNT) injections are commonly used as spasticity treatment in cerebral palsy (CP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised, and the BoNT effect on muscle stem cells remains not well defined. This study aims at clarifying the impact of BoNT on growing muscles (1) by analyzing the in vitro effect of BoNT on satellite cell (SC)-derived myoblasts and fibroblasts obtained from medial gastrocnemius microbiopsies collected in young BoNT-naïve children (t0) compared to age ranged typically developing children; (2) by following the effect of in vivo BoNT administration on these cells obtained from the same children with CP at 3 (t1) and 6 (t2) months post BoNT; (3) by determining the direct effect of a single and repeated in vitro BoNT treatment on neuromuscular junctions (NMJs) differentiated from hiPSCs. In vitro BoNT did not affect myogenic differentiation or collagen production. The fusion index significantly decreased in CP at t2 compared to t0. In NMJ cocultures, BoNT treatment caused axonal swelling and fragmentation. Repeated treatments impaired the autophagic-lysosomal system. Further studies are warranted to understand the long-term and collateral effects of BoNT in the muscles of children with CP.

Botulinum Neurotoxin Type a Injection Combined with Absorbable Punctal Plug Insertion: An Effective Therapy for Blepharospasm Patients with Dry Eye.

Blepharospasm patients often have dry eye manifestations. Botulinum neurotoxin type A (BoNT-A) injection has been the main management for blepharospasm and absorbable punctal plug (APP) insertion is shown to be effective in the treatment of dry eye. However, there have been no studies investigating the combined treatment of BoNT-A and APP in blepharospasm patients with dry eye. In this retrospective study, 17 blepharospasm patients with dry eye treated by BoNT-A injection and 12 receiving BoNT-A plus APP treatment were enrolled. The efficacy was evaluated according to the Jankovic rating scale, Ocular Surface Disease Index (OSDI), fluorescein staining (FL), fluorescein tear break-up time (FBUT) and Schirmer I test (SIT). Both BoNT-A and BoNT-A+APP treatment effectively reduced the functional impairment of blepharospasm. At baseline, all the patients had high OSDI scores (BoNT-A group: 82.48 ± 7.37, BoNT-A+APP group: 78.82 ± 4.60, p = 0.112), but relatively low degrees of FL (BoNT-A group: 3.18 ± 1.01, BoNT-A+APP group: 3.50 ± 1.24, p = 0.466), FBUT (BoNT-A group: 1.71 ± 0.77, BoNT-A+APP group: 2.17 ± 0.58, p = 0.077) and SIT (BoNT-A group: 2.53 ± 0.99, BoNT-A+APP group: 3.17 ± 1.23, p = 0.153). After treatment, OSDI, FL, FBUT and SIT were all obviously restored in the two groups. When comparing the changing rates, only OSDI (BoNT-A group: -52.23% ± 15.57%, BoNT-A+APP group: -61.84% ± 9.10%, p = 0.047) and FL (BoNT-A group: -22.55% ± 25.98%, BoNT-A+APP group: -41.94% ± 14.46%, p = 0.016) showed significant differences between the two groups. This study suggests that OSDI is not applicable in the diagnosis of dry eye among blepharospasm patients. For blepharospasm patients with severe dry eye symptoms, especially those with fluorescein staining in the cornea, the combined treatment of BoNT-A and APP is more effective than using BoNT-A alone.

1. Rare complication of nodular lesions following Botulinum neurotoxin type A injection post SARS-CoV-2 vaccination

Botulinum neurotoxin type A (BoNT-A) is a common non-surgical aesthetic procedure in the United Kingdom. The non-surgical aesthetic industry in the UK is poorly regulated. We report a case of BoNT-A treatment performed by a beautician that cascaded into a series of unfortunate events.

The Short-Term Impact of Botulinum Neurotoxin-A on Muscle Morphology and Gait in Children with Spastic Cerebral Palsy.

Children with spastic cerebral palsy (SCP) are often treated with intramuscular Botulinum Neurotoxin type-A (BoNT-A). Recent studies demonstrated BoNT-A-induced muscle atrophy and variable effects on gait pathology. This group-matched controlled study in children with SCP compared changes in muscle morphology 8–10 weeks post-BoNT-A treatment (n = 25, median age 6.4 years, GMFCS level I/II/III (14/9/2)) to morphological changes of an untreated control group (n = 20, median age 7.6 years, GMFCS level I/II/III (14/5/1)). Additionally, the effects on gait and spasticity were assessed in all treated children and a subgroup (n = 14), respectively. BoNT-A treatment was applied following an established integrated approach. Gastrocnemius and semitendinosus volume and echogenicity intensity were assessed by 3D-freehand ultrasound, spasticity was quantified through electromyography during passive muscle stretches at different velocities. Ankle and knee kinematics were evaluated by 3D-gait analysis. Medial gastrocnemius (p = 0.018, −5.2%) and semitendinosus muscle volume (p = 0.030, −16.2%) reduced post-BoNT-A, but not in the untreated control group, while echogenicity intensity did not change. Spasticity reduced and ankle gait kinematics significantly improved, combined with limited effects on knee kinematics. This study demonstrated that BoNT-A reduces spasticity and partly improves pathological gait but reduces muscle volume 8–10 weeks post-injections. Close post-BoNT-A follow-up and well-considered treatment selection is advised before BoNT-A application in SCP.

Botulinum neurotoxin type A improves vasti muscle balance, patellar tracking, and pain in patients with chronic patellofemoral pain.

The purpose of this study was to determine the effects of botulinum neurotoxin type A (BoNT-A) on vastus lateralis:vastus medialis (VL:VM) muscle balance, patellar tracking, and pain in patients with chronic patellofemoral (PF) pain. We recruited 13 participants (9 females, 4 males) with recalcitrant PF pain who underwent ultrasound-guided BoNT-A injections into the distal third of the VL muscle, followed by a 6-week home exercise program to strengthen their VM muscle. We imaged the participants in a C-arm computed tomography (CT) scanner before and after the intervention. We calculated VL:VM ratios from CT images from a supine, nonweight-bearing condition. We obtained patellar tilt and bisect offset values from CT images from an upright, weight-bearing condition. We recorded functional pain scores before, immediately after, and 2-4 years after the intervention. We classified the participants into normal tracking and maltracking groups based on their patellar tilt and bisect offset values. BoNT-A with home exercise reduced VL:VM ratio (18%; p < 0.001), patellar tilt (19%; p = 0.020), and bisect offset (5%; p = 0.025). Four participants classified as maltrackers before the intervention transitioned to normal tracking after the intervention. Functional pain scores improved immediately after the intervention (13%, p < 0.001) and remained improved at 2-year follow-up (12%, p = 0.011). Statement of Clinical Significance: This study provides new evidence in support of BoNT-A for treatment of PF pain. Classification of patients under weight-bearing conditions may identify individuals who will most benefit from a BoNT-A treatment.

The Lack of Systemic and Subclinical Side Effects of Botulinum Neurotoxin Type-A in Patients Affected by Post-Stroke Spasticity: A Longitudinal Cohort Study.

Botulinum Neurotoxin type-A (BoNT-A) is the treatment of choice for focal post-stroke spasticity (PSS). Due to its mechanism of action and the administration method, some authors raised concern about its possible systemic diffusion leading to contralateral muscle weakness and autonomic nervous system (ANS) alterations. Stroke itself is a cause of motor disability and ANS impairment; therefore, it is mandatory to prevent any source of additional loss of strength and adjunctive ANS disturbance. We enrolled 15 hemiparetic stroke survivors affected by PSS already addressed to BoNT-A treatment. Contralateral handgrip strength and ANS parameters, such as heart rate variability, impedance cardiography values, and respiratory sinus arrythmia, were measured 24 h before (T0) and 10 days after (T1) the ultrasound (US)-guided BoNT-A injection. At T1, neither strength loss nor modification of the basal ANS patterns were found. These findings support recent literature about the safety profile of BoNT-A, endorsing the importance of the US guide for a precise targeting and the sparing of “critical” structures as vessels and nerves.

Reduced Cross-Sectional Muscle Growth Six Months after Botulinum Toxin Type-A Injection in Children with Spastic Cerebral Palsy.

Botulinum Neurotoxin type-A (BoNT-A) injections are widely used as first-line spasticity treatment in spastic cerebral palsy (SCP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised. Yet, the risk of initiating BoNT-A to reduce muscle growth remains unclear. This study investigated medial gastrocnemius (MG) morphological muscle growth in children with SCP (n = 26, median age of 5.2 years (3.5)), assessed by 3D-freehand ultrasound prior to and six months post-BoNT-A injections. Post-BoNT-A MG muscle growth of BoNT-A naive children (n = 11) was compared to (a) muscle growth of children who remained BoNT-A naive after six months (n = 11) and (b) post-BoNT-A follow-up data of children with a history of BoNT-A treatment (n = 15). Six months after initiating BoNT-A injection, 17% decrease in mid-belly cross-sectional area normalized to skeletal growth and 5% increase in echo-intensity were illustrated. These muscle outcomes were only significantly altered when compared with children who remained BoNT-A naive (+4% and −3%, respectively, p < 0.01). Muscle length growth persevered over time. This study showed reduced cross-sectional growth post-BoNT-A treatment suggesting that re-injections should be postponed at least beyond six months. Future research should extend follow-up periods investigating muscle recovery in the long-term and should include microscopic analysis.

Triceps Surae Muscle Characteristics in Spastic Hemiparetic Stroke Survivors Treated with Botulinum Toxin Type A: Clinical Implications from Ultrasonographic Evaluation.

Equinovarus foot is one of the most commonly spasticity related conditions in stroke survivors, leading to an impaired gait and poor functional performances. Notably, spastic muscles undergo a dynamic evolution following typical pathophysiological patterns. Botulinum Neurotoxin Type A (BoNT-A) is the gold standard for focal spasticity treatment, and ultrasound (US) imaging is widely recommended to guide injections and monitor muscle evolution. The role of BoNT-A in influencing muscle fibroadipose degeneration is still unclear. In this study, we analyzed medial gastrocnemius (MG) and soleus (SOL) US characteristics (cross-sectional area, muscle thickness, pennation angle, and mean echo intensity) in 53 patients. MG and SOL alterations, compared to the unaffected side, depend on the spasticity only and not on the BoNT-A treatment. In functionally preserved patients (functional ambulation classification, FAC > 3; modified Ashworth scale, MAS ≤ 2), the ultrasonographic changes of MG compared to ipsilateral SOL observed in the paretic limb alone seems to be due to histological, anatomical, pathophysiological, and biomechanical differences between the two muscles. In subjects with poor walking capability and more severe spasticity, such ipsilateral difference was found in both calves. In conclusion, BoNT-A does not seem to influence muscle degeneration. Similar muscles undergo different evolution depending on the grade of walking deficit and spasticity.

Botulinum Neurotoxin Type A as an Adjuvant to Reduce Scarring After Dermatological Surgery.

Botulinum neurotoxin type A (BoNTA) is thought to have biological effects beyond muscle paralysis, including direct effects on wound healing. This provides a potential rationale for adjuvant intradermal BoNTA injection in selected patients undergoing minor dermatological surgeries, such as sebaceous cyst or intradermal naevus excision, which often lead to problematic scarring. Case studies are presented showing that BoNTA treatment may be associated with more rapid post-procedural healing and less visible scarring. These case reports of adjuvant intradermal BoNTA injection could justify the initiation of prospective trials in this setting. J Drugs Dermatol. 2021;20(6):677-680. doi:10.36849/JDD.5807.

PND37 Cost-Effectiveness of BoNT-A Products for Treatment of Pediatric Spasticity in the United Kingdom

For children with impaired motor function, pain, or other functional difficulties attributable to focal spasticity, the UK National Institute for Health and Clinical Excellence guidelines recommend treatment with botulinum neurotoxin type A (BoNT-A). Two BoNT-A products are licensed for pediatric use in the United Kingdom: abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A), but these treatments differ in terms of doses, costs, and injection frequencies. The objective of this analysis was to evaluate the average expenditure per response obtained with aboBoNT-A or onaBoNT-A for managing pediatric spasticity of the upper (ULS) and lower (LLS) limbs. Cost-effectiveness analyses were conducted for BoNT-A treatment of ULS and LLS in the UK. Effectiveness was defined as response to therapy and was based on data from systematic literature reviews and meta-analyses of randomized controlled trials. BoNT-A dose was based on product label and the average weight of a pediatric (6-year-old) patient in the UK. Injection interval was based on clinical trial data, adjusted to consider differences in use observed in real-world studies of BoNT-A use in adult spasticity. Resource use for responders and non-responders was based on a survey of UK physicians treating pediatric LLS. Unit costs were informed by UK fee schedules. AboBoNT-A resulted in lower annual costs compared with onaBoNT-A for the management of ULS (£487 saved) and LLS (£429 saved). Results were driven by differences in injection intervals and a higher treatment response rate for people receiving aboBoNT-A compared with onaBoNT-A. Total cost per responder was lower for people receiving aboBoNT-A compared with onaBoNT-A (ULS: £37,880 vs. £50,100; LLS: £46,459 vs. £66,037). Results were robust to sensitivity analyses. AboBoNT-A may be a cost-effective choice for treatment of spasticity in children. These findings could help deliver more effective and efficient healthcare in the UK.

PND18 BoNT-As for Adult Spasticity and Cervical Dystonia: Cost-Effectiveness Analysis and the Cost of Response in the United Kingdom

For adults with spasticity or cervical dystonia (CD), treatment with botulinum neurotoxin type A (BoNT-A) has been shown to improve achievement of treatment goals. Considering the costs of available BoNT-A therapies could increase the efficiency of healthcare spending. The objective of this analysis was to evaluate the average expenditures per response obtained with abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for spasticity and CD. Cost-effectiveness analyses were conducted to compare aboBoNT-A and onaBoNT-A for treatment of upper limb spasticity (ULS), lower limb spasticity (LLS), and CD, in the United Kingdom. Effectiveness was defined as response to therapy. Response rates and dosing were based on observational studies for ULS and CD. For LLS, real-world observational data were not available, so response rates were based on systematic literature reviews with meta-analysis of clinical trials and dosing based on UK product labels. BoNT-A treatment intervals were based on real-world data when available (ULS), or otherwise were assumed to follow similar patterns to those observed in clinical trials (LLS and CD). Resource use for responders and non-responders was based on a UK physician survey. Unit costs were informed by UK fee schedules. Compared with onaBoNT-A, aboBoNT-A resulted in lower annual costs per patient for the management of ULS, LLS, and CD (savings of £302, £584, and £422, respectively). Results were driven by differences in injection intervals and a higher treatment response rate for people receiving aboBoNT-A compared with onaBoNT-A. Total cost per responder was lower for patients receiving aboBoNT-A compared with onaBoNT-A (ULS: £43,266 vs £55,416; LLS: £98,962 vs £209,376; CD: £13,883 vs £21,817). Results were robust to sensitivity analyses. With high response rates and low costs, aboBoNT-A may be an efficient choice for treating adult spasticity and cervical dystonia in the UK.

Synergic use of botulinum toxin injection and radial extracorporeal shockwave therapy in Multiple Sclerosis spasticity.

Background and aim:In Multiple Sclerosis (MS) spasticity worsens the patient’s quality of life. Botulinum NeuroToxin TypeA (BoNT-A) is extensively used in focal spasticity, frequently combined with physical therapies. Radial extracorporeal shock waves (rESW) were already used in association with BoNT-A. Considering that loss of efficacy and adverse events are determinants of BoNT-A treatment interruption, this study aimed to evaluate the possibility to prolong BoNT-A’s effect by using rESW in MS focal spasticity.Methods:Sixteen MS patients with spasticity of triceps surae muscles were first subjected to BoNT-A therapy and, four months later, to 4 sections of rESWT. Patients were evaluated before, 30, 90 days after the end of the treatments, by using Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS), and kinematic analysis of passive and active ankle ROM.Results:BoNT-A determined a significant reduction of spasticity evaluated by MAS with a reduction of positive effects after 4months (p<0.05); MTS highlighted the efficacy only 90 days after injection (p<0.05). rESWT decreased MAS values at the end and 30 days later the treatment (p<0.01); MTS values showed instead a prolonged effect (p<0.01). BoNT-A determined a gain of passive and active ankle ROM, persisting along with treatment and peaking the maximum value after rESWT (p<0.05).Conclusions:rESWT can prolong BoNT-A effect inducing a significant reduction of spasticity and improvement in passive and active ankle ROM in MS patients. The use of rESWT following BoNT-A injection is useful to avoid some limitations and to prolong the therapeutic effects of BoNT-A therapy. (www.actabiomedica.it)

Long-term adherence and response to botulinum toxin in different indications.

ObjectiveThe objective of the study was the analysis of adherence and self‐perceived treatment response to long‐term botulinum neurotoxin type A (BoNT‐A) treatment in different neurological indications.MethodsIn this retrospective, monocentric, observational study, cross‐sectional and longitudinal data of 1351 patients documenting 20705 injection appointments at the BoNT outpatient clinic of Heinrich Heine University Duesseldorf between 1989 and 2014 were retrospectively analyzed. Patients had been treated with BoNT for neurological conditions, including cervical dystonia (CD), blepharospasm (BSP), other dystonia (ODT), hemifacial spasm (HFS), and spasticity (SPAS). The parameters longitudinally analyzed for the entire cohort were therapy duration as well as the mean and cumulative BoNT‐A dose. Cross‐sectionally, for subgroups of at least 721, patients’ global self‐perceived quality of health and life, global self‐perceived reduction of symptoms by BoNT‐A treatment as well as the clinical global impression were evaluated. Furthermore, mouse hemidiaphragm assay antibodies (MHDA‐ABs) were analyzed in a subgroup.ResultsThe mean treatment duration was 4.58 years (95% CI 4.32–4.84), and 678 (50.2%) therapy dropouts of 1351 patients occurred within the first 8 years. Therapy adherence and self‐perceived symptom reduction in long‐term BoNT‐A treatment over the years were significantly longer in BSP, HFS, and CD patients than in ODT and SPAS patients.InterpretationThe treatment indication determines long‐term adherence and self‐perceived symptom reduction in BoNT‐A therapy, which are better in BSP, HFS, and CD patients than in ODT and SPAS patients. MHDA‐ABs had a significant impact on global self‐perceived symptom reduction, but with only a limited degree.

Saliva changes in Parkinson\u2019s disease patients after injection of Botulinum neurotoxin type A

Patients with Parkinson’s disease (PD) are compromised by poor oral condition due to oropharyngeal bradykinesia, dysphagia, and the side effects of treatment. Intrasalivary gland injections of Botulinum neurotoxin type A (BNT-A) have been known to treat sialorrhea effectively in these patients. However, the decreased amount of saliva reduces self-cleaning ability that deteriorates oral hygiene and increases dental caries. The aim of this study was to determine the changes in the oral microflora and saliva in patients with PD treated for sialorrhea by means of sonography-controlled BNT-A injections into the bilateral parotid and submandibular glands. Altogether, 38 persons participated in the study: 12 PD patients who were injected with BNT-A for treatment of sialorrhea and passed salivary tests before and 1 month after the injections; and 13 PD patients and 13 healthy subjects who were not injected with BNT-A and passed salivary tests once. The condition of oral health was measured by the amount of saliva, salivary flow rate, and salivary composition. A good outcome with a significant decrease in salivary flow rate occurred at 1-month follow-up in the BNT-A-treated group while no significant change was found in salivary composition. BNT-A treatment did not change the Streptococcus mutans levels in saliva but there was statistically significant increase in levels of Lactobacilli. BNT-A injections can effectively treat sialorrhea while considering the change of oral microflora, and the patients should be under dentists’ care more frequently. EudraCT clinical trial number: 2015-000682-30.

INTEREST IN CD2, a global patient-centred study of long-term cervical dystonia treatment with botulinum toxin

BackgroundLongitudinal cohort studies provide important information about the clinical effectiveness of an intervention in the routine clinical setting, and are an opportunity to understand how a population presents for treatment and is managed.MethodsINTEREST IN CD2 (NCT01753349) is a prospective, international, 3-year, longitudinal, observational study following the course of adult idiopathic cervical dystonia (CD) treated with botulinum neurotoxin type A (BoNT-A). The primary objective is to document long-term patient satisfaction with BoNT-A treatment. Here we report baseline data.ResultsThis analysis includes 1036 subjects (67.4% of subjects were female; mean age was 54.7 years old; mean TWSTRS Total score was 31.7). BoNT-A injections were usually given in line with BoNT-A prescribing information. The most commonly injected muscles were splenius capitis (87.3%), sternocleidomastoid (82.6%), trapezius (64.3%), levator scapulae (40.9%) and semispinalis capitis (26.9%); 35.5% of subjects were injected using a guidance technique. Most subjects (87.8%) had been previously treated with BoNT-A (median interval between last pre-study injection and study baseline was 4 months); of these 84.8% reported satisfaction with BoNT-A treatment at peak effect during their previous treatment cycle and 51.5% remained satisfied at the end of the treatment. Analyses by geographical region revealed heterogeneity in the clinical characteristics and BoNT-A injection practice of CD subjects presenting for routine treatment.ConclusionsThese baseline analyses provide sizeable data regarding the epidemiology and clinical presentation of CD, and demonstrate an international heterogeneity of clinical practice. Future longitudinal analyses of the full 3-year study will explore how these factors impact treatment satisfaction.

Botulinum neurotoxin treatment in children with cerebral palsy: validation of a needle placement protocol using passive muscle stretching and relaxing.

To validate a detailed intramuscular needle placement protocol using passive muscle stretching and relaxing for botulinum neurotoxin type A (BoNT-A) treatment in the lower extremity of children with spastic cerebral palsy (CP), with verification by electrical stimulation. A prospective observational study was performed in 75 children with spastic CP who received regular BoNT-A treatment under general anaesthesia (52 males, 23 females; mean age 8y 9mo, SD 3y 7mo, range 4-18y; mean body mass index 16.2, SD 3.7, range 7.7-26.7). A total of 1084 intramuscular needle placements using passive muscle stretching and relaxing were verified by electrical stimulation. Primary outcome was the positive predictive value. Intramuscular needle placement in the muscles adductor brevis, adductor longus, gracilis, semimembranosus, semitendinosus, biceps femoris, rectus femoris, and lateral and medial heads of the gastrocnemius and soleus had a positive predictive value ranging from 85.7% to 100% (95% confidence interval ranging from 71.5-89.9% to 91.4-100%). This validated detailed protocol for intramuscular needle placement using passive muscle stretching and relaxing for BoNT-A treatment in the lower extremity of children with spastic CP is reliable and has a high positive predictive value.

Treatment with botulinum toxin in children with cerebral palsy: a qualitative study of parents' experiences.

In children with cerebral palsy everyday movements such as walking, standing and using one's hands can be difficult to perform because of spasticity. Botulinum neurotoxin type A (BoNT-A) are often used to reduce spasticity. The aim of this study was to describe how parents of children with cerebral palsy experienced the child's treatment with BoNT-A, how the child was affected by the treatment and how spasticity affected the child. A qualitative study in which 15 parents of children (6-13 years old) with cerebral palsy were interviewed about their experiences of the BoNT-A treatment. The children had received several BoNT-A treatments. An interview guide was used with topics: the child's functions before and after the treatment, the outcomes of the treatment and how they valued the BoNT-A treatment. Content analysis was used to analyse the interviews. The analyses resulted in two themes: 'When softness comes and goes' and 'Both want and do not want'. The reduction of spasticity - softness - was described to promote motor functions, and facilitate the next step in motor development. The children were described as being more active out of their own initiative and having a happier mood. Spasticity, described as stiffness, was described to make walking more strenuous as well as interfering with activities. The BoNT-A injection procedure was perceived as troublesome and painful for the child, and sometimes traumatic for both children and parents. Treatment with BoNT-A was described as facilitating motor development and activity. The children's and the parents' negative experiences of the injection procedure should be addressed.

SPACE: International, non-interventional study of botulinum toxin in treatment of spasticity

Intramuscular injections with botulinum neurotoxin type A (BoNT-A) have become the first-line treatment for most patients with focal and multifocal spasticity. Multiple controlled trials have demonstrated the safety and efficacy of repeated BoNT-A injections for patients with focal spasticity. However, there is a lack of data on treatment approaches in real-life clinical practice and data on which patients in this diverse population are most likely to benefit from BoNT-A treatment. The purpose of the SPAsticity in PractiCE (SPACE) study is to understand how physicians use BoNT in the long-term management of spasticity, to evaluate the safety and efficacy of treatment with BoNT-A in “real-life” clinical practice and to collect information on treating physicians and their treatment preferences and decisions. SPACE is a prospective, non-interventional, open-label, multicenter, multinational study (106 active sites in 9 countries). Participants can receive any number of treatment sessions with any BoNT-A product available in their country, at the discretion of their physician according to individual patients’ needs and physician's routine clinical practice. Internationally 756 patients aged ≥ 18 years were included with spasticity of any aetiology who require BoNT-A injections and who have not been previously treated with BoNT-A or BoNT-B for any indication. In total, 106 active sites and 230 physicians were involved. In France, 126 patients were included, 21 active sites and 24 physicians were involved. Results show that most patients (66.4% overall) had post-stroke spasticity and that the most important key treatment goals were improvements of functionality (especially “in mobility” and “in dexterity and reaching”). SPACE will help to further define the role of BoNT-A as part of a multimodal management approach for focal spasticity and to improve patient treatment according their needs. Data collected will help to identify challenges physicians face in managing patients with focal spasticity.

Multimodal Physiotherapy as an Add-On Treatment to Botulinum Neurotoxin A-Therapy in Patients with Cervical Dystonia

<b>Background:</b> The treatment of choice for cervical dystonia comprises a local injection of botulinum neurotoxin type A (BoNT-A). Whether additional physiotherapy can achieve better results is not clearly documented in the literature. The present study aims to show possible effects of physiotherapy as an add-on treatment to therapy with botulinum neurotoxin type A in terms of pain, severity of dystonia, statics and function of the cervical spine as well as the quality of life in order to optimize the treatment of cervical dystonia. <b>Design/Methods:</b> This is a prospective, single-center, interventional study of a target patient population comprising 20 participants. The study is divided into 2 phases, with each phase lasting for 3 months. During the first phase, the usual BoNT-A will be applied. In addition, the baseline values will be collected and these assessments will be repeated at an interval of 6 weeks. In the second phase, participants will undergo a physiotherapy program consisting of two 45 min sessions per week in addition to the BoNT-A treatment. The assessments will be undertaken at the same intervals as in the first phase. <b>Analysis:</b> In order to determine the effect of the add-on physiotherapy program, the following parameters will be measured for each assessment: quality of life using the SF- 36 score and the range of motion determined by the ZEBRIS measurement system which will comprise the primary endpoints. Furthermore, for each assessment the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and electrical activity from the trapezius and the sternocleidomastoid muscles measured by a surface electromyography will be recorded. Descriptive statistical analysis will be performed for all of the collected data. Possible changes in the measured values will be compared to the baseline values over the 2 periods by means of the Wilcoxon-test at a significance level of p<0.05. For the statistical analysis the software SPSS 22.0 will be used. <b>Trial registration:</b> Deutsches Register Klinischer Studien: DRKS00006562

Transurethral intraprostatic injection of botulinum neurotoxin type A for the treatment of chronic prostatitis/chronic pelvic pain syndrome: results of a prospective pilot double-blind and randomized placebo-controlled study.

To evaluate the effect of botulinum neurotoxin type-A (BoNT-A) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refractory to medical therapy. Between November 2011 and January 2013, 60 men aged ≥18 years with CP/CPPS, and with National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores ≥10 and pain subscale scores ≥8, who were refractory to 4-6 weeks' medical therapy, underwent transurethral intraprostatic injection of BoNT-A or normal saline in a prospective pilot double-blind randomized study. The patients' NIH-CPSI total and subscale scores, American Urological Association (AUA)-symptom score (SS), visual analogue scale (VAS) and quality of life (QoL) scores and frequencies of diurnal and nocturnal urination were evaluated and compared at baseline and at 1, 3 and 6 months after injection and also were compared between the two groups. A total of 60 consecutive patients were randomized to a BoNT-A (treatment) or normal saline (placebo) group. In the treatment group at the 1-, 3- and 6-month evaluation the NIH-CPSI total and subscale scores, and the AUA-SS, VAS and QoL scores, along with frequencies of diurnal and nocturnal urinations, had significantly improved compared with baseline values (P < 0.05). By contrast, in the placebo group, none of these values showed improvement and the values were significantly different from those in the treatment group. Although the differences between the two groups in AUA-SS and frequencies of nocturnal urination were not significant at 1-month follow-up, repeated-measure analysis showed significant improvement in each of these values over the entire follow-up period in the treatment group. The most prominent improvement was related to the pain subscale score, which decreased by 64.76, 75.63 and 79.97% at 1, 3 and 6 months after treatment compared with baseline, followed by the VAS score, which decreased by 62.3, 72.4 and 82.1% at each follow-up, respectively. Only two patients developed mild transient gross haematuria, which was managed conservatively. Transurethral intraprostatic BoNT-A injection maybe an effective therapeutic option in patients with CP/CPPS as it reduces pain and improves QoL.