Botulinum Neurotoxin Type A Injection Research Articles

Assessment of Anticholinergic Use After Fading of BTX-A Effects in Refractory Idiopathic Overactive Bladder: A Prospective Blinded Randomized Trial.

PurposeTo evaluate the efficacy and safety of re-treatment with anticholinergics on refractory idiopathic overactive bladder (OAB) previously treated with intravesical botulinum neurotoxin type A (BTX-A) injections.MethodsOne hundred patients were initially managed by intravesical injections of 100 IU of BTX-A. After the effects of BTX-A faded, patients were randomized into 2 groups: group A patients received solifenacin (10 mg) for 12 weeks (study group), while group B patients received placebo treatment for 12 weeks (control group), then subsequently received solifenacin (10 mg) for another 6 weeks. All patients underwent preoperative urodynamic testing. Patients were asked to complete the validated overactive bladder symptoms score (OABSS) and incontinence quality of life (I-QoL) instruments after the effects of intravesical BTX-A faded and at 12 weeks of follow-up. Univariate and multivariate analyses of the factors affecting treatment response were conducted.ResultsAt 12 weeks of follow-up, in group A, all OABSS items, including the total score, had improved significantly (P<0.0001). Group A had lower frequency and amplitude of detrusor overactivity and detrusor leak point pressure (P<0.0001, P=0.03, and P=0.01, respectively). Cystometric capacity also increased significantly (P=0.007), as did all I-QoL parameters. In a comparison of patients with failed treatment and patients with successful treatment, female sex, repeated intravesical BTX-A injections, and increased bladder capacity were statistically significant (P=0.001, P=0.0001, and P=0.002, respectively). Repeated intravesical BTX-A injections and increased bladder capacity were independent factors predicting treatment success.ConclusionsIn patients with refractory idiopathic OAB, reuse of anticholinergics could be an effective treatment option in patients after the effects of BTX-A fade. Repeated intravesical BTX-A injections and increased cystometric capacity could affect treatment response.

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.

The effect of intradetrusor botulinum neurotoxin type A on urinary NGF, TGF BETA-1, TIMP-2 levels in children with neurogenic detrusor overactivity due to myelodysplasia.

The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia. This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA). Urine samples of each child were collected before and after BoNT-A injections, specifically at the first and third postoperative months. Urine samples were analyzed with ELISA method and NGF, TGF-Beta-1, and TIMP-2 levels were measured. Urine marker levels and clinical findings were assessed for statistical significance with Wilcoxon Signed Ranks Test and Friedman Test. A total of 15 children (5 boys and 10 girls) were assigned as the study group. Mean age of the patients was 7.1 ± 2.5 years (range 2.5-11). A statistically significantly decline was observed in urinary TGF-Beta-1 and NGF levels following BoNT-A injections, compared to the preoperative levels (P < 0.05). TIMP-2 levels also tend to decrease following BoNT-A injections but this was not statistically significant compared to the preoperative levels. This preliminary study, suggests urinary TGF-Beta-1 and NGF as a potent marker in children with NDOA, as they decline following BoNT-A injection. Further studies are needed in identifying their special role in assessing treatment success after invasive interventions.

Botulinum neurotoxin type A alleviates mechanical hypersensitivity associated with infraorbital nerve constriction injury in rats

We investigated the effect of botulinum neurotoxin type A (BoNT-A) on mechanical allodynia and hyperalgesia associated with infraorbital nerve constriction (ION-CCI) in rats. ION-CCI rats received a subcutaneous BoNT-A injection into the whisker pad area on day 7 postoperatively and underwent pain assessment on days 14 and 21 postoperatively. Rats were assigned to one of four treatment groups (n=5 each): ION-CCI+BoNT-A 20pg (low-dose group), ION-CCI+BoNT-A 200pg (high-dose group), ION-CCI+saline, and Sham. Mechanical allodynia and hyperalgesia were evaluated preoperatively (baseline) and on days 7, 14, and 21 postoperatively. After noxious mechanical stimulation of whisker pad skin, the number and distribution pattern of the phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) neurons were analyzed in the trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). On day 21, nocifensive behavior was attenuated by high-dose but not low-dose BoNT-A administration. In addition, after noxious mechanical stimulation of whisker pad skin, the numbers of pERK-IR cells in the superficial laminae of Vc and C1-C2 were significantly lower in the high-dose BoNT-A group than in the ION-CCI+saline group. The present findings suggest that, by suppressing Vc neuronal activity, high-dose intradermal injection of BoNT-A at the site of ION innervation alleviates mechanical facial allodynia and hyperalgesia associated with ION-CCI.

Predicting Improvement in Writer's Cramp Symptoms following Botulinum Neurotoxin Injection Therapy.

IntroductionWriter’s cramp is a specific focal hand dystonia causing abnormal posturing and tremor in the upper limb. The most popular medical intervention, botulinum neurotoxin type A (BoNT-A) therapy, is variably effective for 50–70% of patients. BoNT-A non-responders undergo ineffective treatment and may experience significant side effects. Various assessments have been used to determine response prediction to BoNT-A, but not in the same population of patients.MethodsA comprehensive assessment was employed to measure various symptom aspects. Clinical scales, full upper-limb kinematic measures, self-report, and task performance measures were assessed for nine writer’s cramp patients at baseline. Patients received two BoNT-A injections then were classified as responders or non-responders based on a quantified self-report measure. Baseline scores were compared between groups, across all measures, to determine which scores predicted a positive BoNT-A response.ResultsFive of nine patients were responders. No kinematic measures were predictably different between groups. Analyses revealed three features that predicted a favorable response and separated the two groups: higher than average cramp severity and cramp frequency, and below average cramp latency.DiscussionNon-kinematic measures appear to be superior in making such predictions. Specifically, measures of cramp severity, frequency, and latency during performance of a specific set of writing and drawing tasks were predictive factors. Since kinematic was not used to determine the injection pattern and the injections were visually guided, it may still be possible to use individual patient kinematics for better outcomes.

Predicting Improvement in Writer’s Cramp Symptoms following Botulinum Neurotoxin Injection Therapy

<strong>Introduction:</strong> Writer’s cramp is a specific focal hand dystonia causing abnormal posturing and tremor in the upper limb. The most popular medical intervention, botulinum neurotoxin type A (BoNT-A) therapy, is variably effective for 50–70% of patients. BoNT-A non-responders undergo ineffective treatment and may experience significant side effects. Various assessments have been used to determine response prediction to BoNT-A, but not in the same population of patients. <strong>Methods:</strong> A comprehensive assessment was employed to measure various symptom aspects. Clinical scales, full upper-limb kinematic measures, self-report, and task performance measures were assessed for nine writer’s cramp patients at baseline. Patients received two BoNT-A injections then were classified as responders or non-responders based on a quantified self-report measure. Baseline scores were compared between groups, across all measures, to determine which scores predicted a positive BoNT-A response. <strong>Results:</strong> Five of nine patients were responders. No kinematic measures were predictably different between groups. Analyses revealed three features that predicted a favorable response and separated the two groups: higher than average cramp severity and cramp frequency, and below average cramp latency. <strong>Discussion:</strong> Non-kinematic measures appear to be superior in making such predictions. Specifically, measures of cramp severity, frequency, and latency during performance of a specific set of writing and drawing tasks were predictive factors. Since kinematic was not used to determine the injection pattern and the injections were visually guided, it may still be possible to use individual patient kinematics for better outcomes.

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.

Does Botulinum neurotoxin type A treatment for sialorrhea change oral health?

Botulinum neurotoxin type A (BNT-A) intrasalivary gland injections in patients with neurological disorders have been known to effectively treat hypersalivation. However, oral health can be compromised with increasing the dose. The aim of this study was to find out the therapeutic effect of low-dose, ultrasonography-controlled BNT-A injections into the bilateral parotid and submandibular glands on oral health in the treatment of sialorrhea. Twenty patients diagnosed with Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and other neurological disorders, including stroke or birth trauma, received BNT-A injections with salivary tests before and 1month after the injections. Drooling was evaluated using subjective scales and objective assessment of salivary flow rate and oral health (salivary composition and cariogenic bacterial counts). A significant decrease was found in salivary flow rate at 1- and 3-month follow-up in the BNT-A treated group. There was no significant change in salivary composition or cariogenic bacterial counts. BNT-A injections according to the current protocol can effectively manage sialorrhea while maintaining oral health. Oral health can be considered the mirror of general human health, as the cause of many diseases. Saliva plays a crucial role in protecting the oral cavity. The present study is of high clinical relevance because, although earlier research has proved the effect of Botulinum neurotoxin type A injections on reduction in saliva flow, data about the risks of the treatment method to the oral condition through affecting saliva composition has so far been missing.

Frequency and characteristics of goal attainment following BoNT-A injection for management of spasticity

Purpose: To determine which Goal Attainment Scale (GAS) goals are commonly achieved in patients with upper limb and/or lower limb spasticity following Botulinum Neurotoxin Type A (BoNT-A) injection.Method: Adults who attended a Spasticity Management Clinic for upper and/or lower limb BoNT-A injection were included in this prospective cohort study. Goals were set by participants and/or carers in conjunction with the therapist using the GAS, prior to injection and reviewed at one month following the injection. Three out of the five categories of goals were passive. Goals were categorised into: mobility/transfers, pain/comfort, upper limb use, hygiene, and cosmesis. The number of responders for the GAS total score, and in each of the GAS categories, was calculated.Results: Sixty-seven participants were recruited (mean age 51 ± 16 years; range 18–85), 70% had a stroke. Responders for mobility and transfer goals were further post injury or disease onset than non-responders (median 5.9 vs. 1.2 years, p = 0.03). Clients with stroke were less likely than other participants to achieve mobility and transfer goals (p = 0.02). There was a trend for those who achieved mobility and transfer goals to be younger (mean 49 years vs. 55 years, p = 0.06). Although active goals are more commonly identified, passive goals were more likely to be achieved.Conclusions: Although active goals are commonly identified by people with spasticity, passive goals were more likely to be achieved following BoNT-A injection. A long duration of spasticity does not preclude patients from achieving mobility and transfer goals. Non-stroke participants were more likely to achieve mobility and transfer goals.Implications for RehabilitationPatients with chronic spasticity should be considered for BoNT-A as clinically meaningful outcomes can be achieved.When spasticity is present in multiple muscles, the GAS can be an assistive tool to guide clinicians in determining which muscles are a priority for injection, because the client will be more motivated to improve those specific goals.Although carers and patients are more willing to set active goals, these are more difficult to achieve possibly because follow up intervention or independent practise is required.

Characterizing the Lateral Border of the Frontalis for Safe and Effective Injection of Botulinum Toxin.

The forehead is a common site for injection of botulinum neurotoxin type A (BoNT-A) to treat hyperactive facial muscles. Unexpected side effects of BoNT-A injection may occur because the anatomy of the forehead musculature is not fully characterized. The authors described the lateral border of the frontalis in terms of facial landmarks and reference lines to determine the safest and most effective forehead injection sites for BoNT-A. The hemifaces of 49 embalmed adult Korean cadavers were dissected in a morphometric analysis of the frontalis. L2 was defined in terms of FT (the most protruding point of the frontotemporal region), L0 (the line connecting the infraorbital margin with the tragus), and L1 (the line parallel to L0 and passing through FT) such that L2 was positioned 45° from L1 and passed through FT. The distance from FT to the superior margin of the orbicularis oculi was 12.3 ± 3.3 mm. The frontalis extended more than 5 cm along L2 in 49 of 49 cases (100%), more than 6 cm in 47 cases (95.9%), more than 7 cm in 34 cases (69.4%), more than 8 cm in 11 cases (22.4%), and more than 9 cm in 3 cases (6.1%). The lateral border of the frontalis ran parallel to and within 1 cm of the medial side of L2. Surface anatomy mapping can assist with predicting the lateral border of the frontalis to minimize the side effects and maximize the efficiency of BoNT-A injections into the forehead.

A Double-Blind Randomized Controlled Trial Investigating the Most Efficacious Dose of Botulinum Toxin-A for Sialorrhea Treatment in Asian Adults with Neurological Diseases.

This study aims to determine the most efficacious dose of Botulinum neurotoxin type A (BoNT-A) in reducing sialorrhea in Asian adults with neurological diseases. A prospective, double-blind randomized controlled trial was conducted over 24 weeks. Thirty patients with significant sialorrhea were randomly assigned to receive a BoNT-A (Dysport®) injection into the submandibular and the parotid glands bilaterally via an ultrasound guidance. The total dose given per patient was either BoNT-A injection of (i) 50 U; (ii) 100 U; or (iii) 200 U. The primary outcome was the amount of saliva reduction, measured by the differential weight (wet versus dry) of intraoral dental gauze at baseline and at 2, 6, 12, and 24 weeks after injection. The secondary outcome was the subjective report of drooling using the Drooling Frequency and Severity Scale (DFS). Saliva reduction was observed in response to all BoNT-A doses in 17 patients who completed the assessments. Although no statistically significant difference among the doses was found, the measured reduction was greater in groups that received higher doses (100 U and 200 U). The group receiving 200 U of Dysport® showed the greatest reduction of saliva until 24 weeks and reported the most significant improvement in the DFS score.

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.

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.

Effects of Botulinum Toxin A Injection on Healing and Tensile Strength of Ruptured Rabbit Achilles Tendons

Tendon lacerations are most commonly managed with surgical repair. Postoperative complications such as adhesions and ruptures often occur with immobilization. Early postoperative mobilization is therefore advised to minimize complications and time required to return to daily life. The aim of this study was to evaluate whether botulinum neurotoxin type-A (BoNT-A) can be used to enhance healing and prevent rupture in mobilized animals with Achilles tenotomy. Twenty-seven rabbits were divided into 3 groups, namely, I, II, and III, after surgical 1-sided Achilles tenotomy and end-to-end repair. The control group for biomechanical comparisons consisted of randomly selected contralateral (unoperated) healthy Achilles tendons. Group I received BoNT-A (4 U/kg) injection into the calf muscles. One week later, electromyographical confirmation was performed to establish the effects of injection. Surgery was then performed. Animals in the second group (n = 9, group II) were immobilized with a cast postoperatively. The third group (n = 9, group III) was mobilized immediately with no cast or BoNT-A. Tendons were harvested and gap formation or ruptures as well as strength of the repaired tendon were assessed 6 weeks after surgery. Achilles tendons healed in all animals injected with BoNT-A, whereas all were ruptured in group III. All Achilles tendons of animals in groups I and II healed. However, group I repaired tendons were biomechanically equivalent to healthy tendons, whereas group II repaired tendons demonstrated significantly decreased tensile strength (P = 0.009). The present study suggests that local injection of BoNT-A can be used for treatment of tendon rupture and may replace the use of cast for immobilization. However, further studies are needed to determine whether BoNT-A injection can have a beneficial effect on the healing of tendon repairs in humans.

Clinical outcomes of individualized botulinum neurotoxin type A injection techniques in patients with essential blepharospasm.

PurposeTo assess the clinical outcomes following botulinum neurotoxin type A (BoNT-A) treatment with an individualized injection technique based on the types of spasms and to compare the results of the individualized injection technique with those of the conventional injection technique in the same patients.MethodsFrom November 2011 to July 2013, 77 BoNT-A injections were performed in 38 patients. Eighteen patients were treated with conventional BoNT-A injections before 2011, and 20 patients were referred to our hospital for unsatisfactory results after a conventional injection technique. We classified the patients by spasm-dominant sites: the lateral orbital area, representing the orbital orbicularis-dominant group (ODG); the glabella, representing the corrugator-dominant group (CDG); and the ptosis, representing the palpebral part of the orbicularis-dominant group (PDG). We increased the injection dose into the spasm-dominant sites of the blepharospasm groups. We assessed subjective symptom scores (functional disability score, FDS) after treatment.ResultsThis study included 38 patients (26 women, 12 men; mean age, 60.6 ± 10.9 years). There were 21 patients in the ODG, 10 patients in the CDG, and 7 patients in the PDG. Mean ages were 59.7 ± 12.6, 59.8 ± 8.5, and 66.8 ± 9.0 years, and mean BoNT-A injection dose was 38.8 ± 11.2, 38.8 ± 11.2, and 38.8 ± 10.8 U in each group, respectively (p = 0.44, 0.82 Kruskal-Wallis test). Mean FDS after injection was 1.7 ± 0.7 in the ODG, 1.4 ± 0.8 in the CDG, and 1.2 ± 0.3 in the PDG. There were significant differences in reading and job scale among the three groups. In a comparison between the conventional and individualized injection techniques, there was a significant improvement in mean FDS and in the reading scale in the PDG with the individualized injection technique. The success rate was 92.1% in the conventional injection group and 94.1% in the individualized injection group.ConclusionsThe individualized injection technique of BoNT-A according to the spasm-dominant site is an effective and safe treatment method for essential blepharospasm patients.

Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats.

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

116. Functional connectivity between cortical speech network and primary motor cortex is abnormal in spasmodic dysphonia

In healthy humans, the execution of linguistic tasks modifies the excitability of the hand area of the dominant primary motor cortex (M1), as tested by TMS. Our aim was to investigate the effect of linguistic tasks on the excitability of the M1 in patients with adductor type-spasmodic dysphonia (ASD), before and after Botulinum Neurotoxin Type A (BoNT-A) injections. We studied 10 patients with ASD and 10 age-matched healthy subjects. All participants were right handed. The excitability of either M1 hand area was evaluated at the baseline and during different linguistic and non-linguistic tasks: (1) reading aloud of single words; (2) silent reading; (3) looking at meaningless non-letter strings; (4) oral movements without vocalization; (5) producing simple syllabic phonation. In healthy controls, the motor evoked potential (MEP) elicited by TMS of the dominant M1 were significantly larger during reading aloud. In ASD patients, MEP enhancement in the dominant hand emerged not only during reading aloud but also during syllabic phonation. BoNT-A injections restored the neurophysiologic abnormalities. We conclude that ASD is characterized by an abnormal excitability of the hand area of the dominant M1 during specific linguistic tasks. This likely reflects an altered functional connectivity between cortical speech network and M1.

Use of Botulinum Toxin Type A in the Management of Neonatal Brachial Plexus Palsy

To evaluate functional outcomes and the impact on surgical interventions after the use of botulinum neurotoxin type A (BoNT-A) for muscle imbalance, cocontractions, or contractures with neonatal brachial plexus palsy. A retrospective cohort study. A brachial plexus center in a tertiary children's hospital. Fifty-nine patients with neonatal brachial plexus palsy (75 injection procedures, 91 muscles and/or muscle groups) received BoNT-A injections (mean age at injection, 36.2 months; range, 6-123 months; 31 boys; 30 right-sided injuries, 28 left-sided injuries, 1 bilateral injury). Data collected retrospectively from medical records, from procedure notes andclinic visits before BoNT-A use, at≤6 months follow-up (BoNT-A active [BA]) andat≥7 months follow-up (BoNT-A not active [BNA]) included demographics, injection indication, side, and site(s), previous surgical history, occupational therapy and/or physical therapy plan, and outcome measurements. Outcomes assessed before and after injections included active and passive range of motion, Mallet and Toronto scores, parent comments about arm function, preinjection surgical considerations, and postinjection surgical history. Injection procedures included 51 to shoulder internal rotators, 15 triceps, 15 pronator teres, 9 biceps, and 1 flexor carpi ulnaris. Active and passive shoulder external rotation (SER) range of motion improved after shoulder internal rotator injections (P=.0003 and P= .002, respectively), as did Mallet scores with BA; the latter were sustained with BNA. Surgical intervention was averted, modified, or deferred after BoNT-A in 45% (n= 20) under surgical consideration before BoNT-A. Active elbow flexion improved in 67% (P= .005), sustained BNA (P= .004) after triceps injections; 2 of 7 patients averted surgery. Active supination improved with BA (P= .002), with gains sustained BNA (P=.016). Passive elbow extension improved after biceps injections by an average 17° (P= .004) BA, although not sustained BNA. BoNT-A is an effective adjunct to therapy and surgery in managing muscle imbalance, cocontractions, and contractures in neonatal brachial plexus palsy. Use of BoNT-A can result in averting, modifying, or deferring surgical interventions in a number of affected children.

The effects of botulinum toxin injection frequency on calf muscle growth in young children with spastic cerebral palsy: A 12-month prospective study

This study was a 12-month prospective investigation of changes in the medial gastrocnemius (MG) muscle morphology in children aged 2-5years with spastic cerebral palsy (CP) who had received no previous intramuscular injections of botulinum neurotoxin type-A (BoNT-A) and were randomised to receive either single or multiple (three) BoNT-A injections to the gastrocsoleus. MG morphological changes were compared to age-matched typically developing (TD) peers. Thirteen children with spastic CP with a mean age of 45 (15) months and 18 TD children with a mean age of 48 (14) months participated in the study. The principal outcome measures were MG muscle volume, fascicle length, pennation angle and physiological cross-sectional area (PCSA), which were obtained using 2D and 3D ultrasound. The single and multiple injection frequency groups significantly increased MG muscle volume at 12months relative to the baseline by 13 and 15%, respectively. There were no significant differences in the MG muscle volume 28.5 (12.3) versus 30.3 (3.8)ml, fascicle length 48.0 (10.4) versus 44.8 (1.2)mm or PCSA 7.0 (1.2) versus 6.6 (1.7)cm(2) between the single and multiple injection groups, respectively, at 12months follow-up. The change in MG muscle volume in the single and multiple injection groups was significantly lower than the TD peers by 66 and 60%, respectively. In young children with spastic CP, naive to BoNT-A treatment, MG muscle growth over 12months does not appear to be influenced by intramuscular BoNT-A injection frequency. However, MG muscle growth in the spastic CP groups was significantly lower than the age-matched TD peers. It is unclear whether this is an effect of intramuscular BoNT-A injections or reduced growth rates in children with spastic CP in general. Controlled investigations and longitudinal studies with multiple measurement time points are required in order to determine the influence of BoNT-A treatment on muscle physiological and mechanical growth factors in young children with spastic CP.