BTX Injections Research Articles

Quantification and Monitoring of the Effect of Botulinum Toxin A on Paretic Calf Muscles of Children With Cerebral Palsy With MRI: A Preliminary Study.

Background: Muscles from patients with cerebral palsy (CP) are often spastic and form contractures that limit the range of motion. Injections of botulinum toxin A (BTX) into the calf muscles are an important treatment for functional equinus; however, improvement in gait function is not always achieved. BTX is also used to test muscle weakening for risk evaluation of muscle lengthening surgery. Our aim was to assess the effect of BTX over time on calf muscle properties in pediatric CP patients with MRI.Material and Methods: Six toe-walking CP patients (mean age 11.6 years) with indication for lengthening surgery were prospectively enrolled and received BTX injections into the gastrocnemius and soleus muscles. MRI scans at 3T of the lower legs and clinical examinations were performed pre-BTX, 6 weeks (6w), and 12 weeks (12w) post-BTX. A fat-suppressed 2D multi-spin-echo sequence was used to acquire T2 maps and for segmentation. Fat fraction maps were calculated from 3D multi-echo Dixon images. Diffusion tensor imaging (DTI) with a 2D echo-planar imaging (EPI) sequence yielded maps of the mean apparent diffusion coefficient (ADC) and of the fractional anisotropy (FA). Hyperintense regions of interest (ROIs) on the T2-weighted (T2w) images at 6w were segmented in treated muscles. Mean values of T2, fat fraction, ADC, and FA were calculated in hyperintense ROIs and in reference ROIs in non-treated muscles.Results: Hyperintensity on T2w scans and increased T2 (group mean ± standard deviation: 35 ± 1 ms pre-BTX, 45 ± 2 ms at 6w, and 44 ± 2 ms at 12w) were observed in all patients at the injection sites. The T2 increase was spatially limited to parts of the injected muscles. FA increased (0.30 ± 0.03 pre-BTX, 0.34 ± 0.02 at 6w, and 0.36 ± 0.03 at 12w) while ADC did not change in hyperintense ROIs, indicating a BTX-induced increase in extracellular space and a simultaneous decrease of muscle fiber diameter. Fat fraction showed a trend for increase at 12w. Mean values in reference ROIs remained unchanged.Conclusion: MRI showed limited spatial distribution of the BTX-induced effects in pediatric CP patients. It could be a promising non-invasive tool for future studies to test BTX treatment protocols.

Intradetrusor botulinum toxin injections (300 units) for the treatment of poorly compliant bladders in patients with adult neurogenic lower urinary tract dysfunction.

To evaluate the therapeutic effects of intradetrusor onabotulinum toxin A (BTX) injections in patients with adult neurogenic lower urinary tract dysfunction (ANLUTD) and medically refractory poorly compliant bladders. We retrospectively evaluated patients with urodynamic studies (UDS)-proven, medically refractory impaired bladder compliance (≤20 mL/cm H2 O) secondary to spinal myelopathy treated with 300 units of BTX cystoscopically injected into the detrusor muscle. Objective improvement in compliance was defined as an increase ≥5 mL/cm H2 O on repeat urodynamics. Characteristics were compared between patients who demonstrated symptomatic and objective improvement following treatment versus those without. Seventy-one individuals were included in the final analysis. Mean patient age was 37.2 years (range: 18-78) and ANLUTD duration was 14.5 years (range: 1-34). Average pre-injection bladder compliance was 9.2 mL/cm H2 O (range: 3.0-16.7). After treatment with BTX, 37 of 71 (52%) patients reported subjective reductions in lower urinary tract symptoms. Repeat UDS demonstrated objective bladder compliance improvements in 22 of 71 (31%). Individuals with shorter time intervals since neurologic injury responded better to BTX than those with longer durations (P = .032). BTX injections significantly improved symptoms and bladder compliance in 31% of ANLUTD patients with medical refractory poorly compliant bladders.

A comparative study between sacral neuromodulation and intravesical botulinum toxin injection for patients with refractory overactive bladder

ABSTRACT Objective To compare the efficacy, safety, patient compliance and quality of life (QoL) (early and at 6 months after treatment), in a group of Iraqi female patients with refractory overactive bladder (OAB), treated with intradetrusor botulinum toxin A (BTX) injections vs sacral neuromodulation (SNM). Patients and methods A prospective, clinical interventional study of 37 female patients assessed by history, physical examination, voiding diary, ultrasonography (US), and urodynamics. The patients were assigned to one of two groups: Group 1, treated with cystoscopic BTX injections; and Group 2, treated with SNM. Response to treatment was assessed by voiding diary, the Treatment Benefit Scale, a modified Quality of Life scale, urine culture, and abdominal US. Results The mean age of the patients in Group 1 (BTX) was 43.8 years and in Group 2 (SNM) was 37.2 years. OAB-wet was diagnosed in 11 patients in Group 1 and 10 in Group 2. At the 6-month follow-up there were 14/16 and 12/15 positive responders, in groups 1 and 2, respectively; with no major complications. All the responders had a significant improvement in their overall QoL after both types of treatment. Conclusions Both BTX and SNM, in our experience, were safe and effective in managing our patients with refractory OAB after 6 months of follow-up, which was also reflected by an improvement in their QoL. Abbreviations BTX: botulinum toxin A; IPG: implantable pulse generator; OAB: overactive bladder; PVR: post-void residual urine; QoL: quality of life; SNM: sacral neuromodulation; UDS, urodynamics; UI, urinary incontinence

Botulinum toxin can help with foot symptoms in patients with pachyonychia congenita

Pachyonychia congenita (PC) is a rare genetic skin disease which is estimated to affect between 5,000 and 10,000 people worldwide. PC can cause severe pain, especially affecting weight-bearing areas, which accompanies thickening of the skin on the feet (keratoderma). Although there are options for treating the various symptoms of PC, most of them are not especially effective at improving the keratoderma and the pain. The successful use of botulinum toxin (Btx) injections for treating keratoderma in PC patients has been documented in three reports over the past decade. The injection technique, doses of Btx, and methods of anesthesia varied between the reports and the patients. In recent years, the authors, who are based in Israel, have adopted the same approach and refined the injection technique and anesthesia procedure, and have adjusted the Btx doses to improve the treatment. The purpose of this study was to describe the authors four-year experience during which they administered a total of 30 Btx injections to five PC patients following the protocol they have designed. The conclusions of the study were that Btx treatment of PC-associated keratoderma following an optimized protocol leads to a major change in patients’ quality of life. The best improvement scores concerned patients’ morning feet burning and ability of long-distance walking (> 500 m). The scores were significantly better if the intervals between Btx injections were less than 100 days. This is a summary of the study: A treatment protocol for botulinum toxin injections in the treatment of pachyonychia congenita-associated keratoderma

A treatment protocol for botulinum toxin injections in the treatment of pachyonychia congenita‐associated keratoderma

Severely debilitating plantar keratoderma pain is the most distressing clinical feature of pachyonychia congenita (PC). Several earlier publications have reported therapeutic success with plantar injections of botulinum toxin (Btx). To describe our 4-year experience during which we administered a total of 30 plantar Btx injections to five patients with PC following an optimized protocol. Five patients with PC (age 21-54 years) who were treated at our medical centre from April 2015 to June 2018 were included in the study. After an ultrasound-guided nerve block performed by an anaesthesiologist, the patients received plantar intradermal injections of Btx A. To ascertain the effect of the treatment, we used a dedicated quality-of-life questionnaire for patients with PC (PCQoL) and asked the patients to evaluate the intensity of eight parameters pertaining to their symptoms at baseline and before every treatment session. At study closure, patients were asked to evaluate the maximal improvement in the same eight parameters throughout the study period. All patients demonstrated a decrease in PCQoL scores during the follow-up period. All patients showed a significant improvement in PCQoL after the first treatment session and at the last evaluation (P = 0·043). The scores with the best improvement concerned morning feet burning and long-distance walking (> 500 m). The scores were significantly lower if the intervals between Btx injections were <100 days. Btx treatment of PC-associated keratoderma following an optimized protocol leads to a major change in patients' quality of life. What's already known about this topic? Plantar pain is considered by patients to be the most severe and debilitating manifestation of pachyonychia congenita (PC). Over the past few years, a number of reports have shown that plantar injections of botulinum toxin (Btx) reduce or even eliminate pain, blistering and callosities in patients with PC. However, the injection technique, doses of Btx and methods of anaesthesia varied between reports and patients. What does this study add? Here we report our 4-year experience in providing 30 treatments to five patients following an optimized protocol. Btx was found to provide a quantifiable improvement in all patients treated. What is the translational message? Btx treatment of PC-associated keratoderma using a structured approach, which includes the use of a sufficient dose of Btx (200-400 U of onabotulinumtoxinA or 500-1000 U of abobotulinumtoxinA), and regular intervals between treatment sessions (of < 100 days), leads to a major change in patients' quality of life.

Urinary tract infection and drug-resistant urinary tract infection after intradetrusor onabotulinumtoxinA injection versus sacral neuromodulation

Intradetrusor onabotulinumtoxinA (BTX) and sacral neuromodulation (SNM) are effective treatments for refractory urgency urinary incontinence/overactive bladder (UUI/OAB). BTX carries a risk of urinary tract infection (UTI), which is concerning for the development of multidrug resistant (MDR) UTI. We hypothesized that BTX might carry a higher risk of UTI and MDR UTI compared with SNM and that UTI and MDR UTI risk might increase after repeat BTX injection. This retrospective cohort study included women undergoing BTX or SNM for refractory UUI/OAB in 2012-2016. UTI and MDR UTI were assessed up to 1year post-treatment or until repeat treatment and compared between initial BTX and SNM and between repeat BTX injections. Univariate analyses included Chi-squared and Fisher's exact tests and generalized linear models (GLM) with logit link function. Multivariate analyses used GLM to assess the best predictor variables for any UTI. One hundred and one patients were included (28 BTX, 73 SNM). Rates of UTI (39.3% [95% CI 21.5, 59.4] BTX vs 37.0% [95% CI 26.0, 49.1] SNM) were similar in the two groups at all time intervals. One MDR UTI occurred after SNM. Risk of UTI did not increase with repeat BTX (11 out of 28 [39.3%], 6 out of 17 [35.3%], and 4 out of 7 [57.1%] after 1, 2, and ≥ 3 treatments respectively; p= 0.62). Multivariate analysis found that history of recurrent UTI (OR 2.5, 95%CI 0.98-6.39) and prolapse repair (OR 4.6, 95%CI 1.23-17.07) had increased odds of UTI. Rates of UTI were similar in patients undergoing BTX and SNM. MDR UTI was rare. Patients with prior prolapse repair or recurrent UTI may be at a higher risk of UTI after either procedure.

Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial

BackgroundUrgency urinary incontinence (UUI) is a chronic condition for which sacral neuromodulation (SNM) (InterStim/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/Allergan) are utilized. These therapies have not been compared over extended time. ObjectiveTo compare UUI episodes (UUIE) over 24 mo following SNM or BTX. Design, setting, and participantsMulticenter, open-label, randomized, extension trial (February 2012–July 2016) at nine US medical centers involving 386 women with ≥6 UUIE over 3 d inadequately managed by medications. Participants were clinical responders to treatment: ≥50% reduction in UUIEs after SNM placement or 1 mo post BTX. InterventionSNM (n=194) versus 200 U BTX (n=192). SNM reprogrammings occurred throughout the 24 mo. After 6 mo, two additional BTX injections were allowed. Outcome measurements and statistical analysisPrimary outcome: change in mean daily UUIE over 24 mo. Secondary outcomes: no UUIE, ≥75% and ≥50% UUIE reduction; Overactive Bladder Questionnaire Short Form; Urinary Distress Inventory short form; Incontinence Impact Questionnaire; Patient Global Impression of Improvement; Overactive Bladder Satisfaction of Treatment Questionnaire; and adverse events (AEs). Primary analysis used a linear mixed model. Results and limitationsOutcome data were available for 260/298 (87%) clinical responders. No difference in decreased mean UUIE was found over 24 mo (−3.88 vs −3.50 episodes/d,95% confidence interval [CI]=−0.14–0.89; p=0.15), with no differences in UUI resolution, ≥75% or ≥50% UUIE reduction. BTX group maintained higher satisfaction (mean difference=−9.14, 95% CI=−14.38–−3.90; p<0.001), treatment endorsement (mean difference=−12.16, 95% CI=−17.7–−6.63; p<0.001) through 24 mo. Other secondary measures did not differ. Recurrent urinary tract infections (UTIs) were higher after BTX (24% vs 10%; p<0.01), 6% required intermittent catheterization post second injection. SNM revision and removals occurred in 3% and 9% patients, respectively. ConclusionsBoth treatments offered sustainable UUI improvement, and higher BTX dosing had low clean intermittent catheterization rates, but with UTI risk. SNM revision/removal rates were low due to standardized lead placement with strict treatment response definitions. Patient summaryWe compared a large group of US women with severe urgency urinary incontinence (UUI) who received sacral neuromodulation (InterStim) or onabotulinumtoxinA (Botox A) therapy during a 2-yr period. We found that both therapies had similar success in reducing UUI symptoms, and adverse events were low. However, women in the BotoxA group had higher satisfaction and endorsement with their treatment, but with a higher chance of a urinary tract infection. We conclude that both therapies offer sustained reduction in daily incontinence over 2 yr.

Pharyngeal Dystonia Mimicking Spasmodic Dysphonia

The aim of this study was to describe the presentation of pharyngeal dystonia (PD), which can occur as a focal or segmental dystonia with a primarily pharyngeal involvement for the discussion of treatment methods for controlling consequent symptoms. PD is specific to speech-related tasks. A retrospective medical record review of four patients with PD was performed. All patients were initially misdiagnosed with adductor spasmodic dysphonia and failed standard treatment with botulinum toxin type A (BTX). On laryngoscopy, the patients were discovered to have segmental or focal dystonia primarily affecting the pharyngeal musculature contributing to their vocal manifestations. A novel treatment regimen was designed, which involved directing BTX injections into the muscles involved in spasmodic valving at the oropharyngeal level. After titrating to an optimal dose, all patients showed improvement in their voice and speech with only mild dysphagia. These patients have maintained favorable results with repeat injections at 6- to 12-week intervals. PD, or dystonia with predominant pharyngeal involvement, is a rare entity with vocal manifestations that are not well described. It can be easily mistaken for spasmodic dysphonia. PD is specific to speech-related tasks. A novel method of BTX injections into the involved muscles results in a significant improvement in voice without significant dysphagia.

Does Botulinum Toxin A Treatment Enhance the Walking Pattern in Idiopathic Toe-Walking?

Objective We conducted a randomized controlled trial to evaluate whether a combination of repeated botulinum toxin A (BTX-A) and conservative treatment is more effective in decreasing toe-walking than conservative treatment alone at 24 months follow-up. Patients and Methods Children between 2 and 9 years of age were randomized either into the conservative (CO) or botulinum treatment (BTX) group. The treatment in the CO group consisted of firm shoes, night splints, a home stretching program and physiotherapy. The BTX arm had all the same conservative treatments added with calf muscle BTX-A injections repeated in 6 months intervals if needed. Change in toe-walking pattern, ankle range of movement (ROM), and overall function were assessed at baseline and 6, 12, 18, and 24 months posttreatment. Results A total of 30 toe-walkers participated: 14 in CO and 16 in BTX group. At 24 months, all children in the BTX group and 85% in the CO group evaluated by the blinded physiotherapist (p = 0.065), 75% in the BTX group and 70% in the CO group graded by the research physiotherapist (p = 0.730), and 50% in the BTX group and 54% in the CO group reported by the parents ceased toe-walking (p = 0.837). The most prominent change was noted during the 1st year. The BTX group seemed to reach the goal earlier. No significant differences between the treatment groups in function or in ankle ROM ensued. Conclusion Adding BTX injections did not significantly enhance the goal to walk either flat foot or with heel strike at 24 months posttreatment.

Vertical Trabeculae are Thinned More Than Horizontal Trabeculae in Skeletal-Unloaded Rats.

Skeletal unloading results in a rapid thinning of the trabecular bone network, but it is unknown whether vertical and horizontal trabeculae are equally affected. Therefore, the purpose of the present study was to investigate whether horizontal and vertical trabeculae were thinned similarly during skeletal unloading in rats. Fifty-seven 16-week-old female Wistar rats were randomized into six groups: baseline; control 4 weeks; botulinum toxin A (BTX) 4 weeks; control 8 weeks; BTX 8 weeks; and two BTX injections 8 weeks (BTX + BTX8). The BTX animals were injected in the right hind limb with 4 IU BTX at the start of the study, while the BTX + BTX8 were also injected with 2 IU BTX after 4 weeks. The animals were killed after 0, 4, or 8 weeks. The distal femoral metaphyses were μCT scanned, and the strengths of the femoral necks, mid-diaphyses, and distal femoral metaphyses were ascertained. Disuse resulted in a significant loss of BV/TV, thinning of the trabeculae, and decrease in the degree of anisotropy, and in a significant reduced bone strength after both 4 and 8 weeks. The ratio of horizontal to vertical trabecular thickness (Tb.Th.horz/Tb.Th.vert) and the ratio of horizontal to vertical bone volume (BV.horz/BV.vert) were significantly higher in BTX animals than in control animals. In addition, the horizontal and vertical trabecular thickness probability density functions were more similar in BTX animals than in control animals. In conclusion, skeletal unloading decreased BV/TV, Tb.Th, the degree of anisotropy, and mechanical strength, while BV.horz/BV.vert and Tb.Th.horz/Tb.Th.vert were increased. This indicates that the more loaded vertical trabeculae are pronouncedly more thinned than the less loaded supporting horizontal trabeculae during unloading.

Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis

In man, botulinum toxin type A (BTX) is injected in masticatory muscles for several indications such as trismus, bruxism, or masseter hypertrophy. Bone changes in the mandible following BTX injections in adult animal have therefore became a subject of interest. The aim of this study was to analyze condylar and alveolar bone changes following BTX unilateral injections in masseter and temporal muscles in adult rats. Mature male rats (n=15) were randomized into 2 groups: control (CTRL; n=6) and BTX group (n=9). Rats of the BTX group received a single injection of BTX into right masseter and temporal muscles. Rats of the CTRL group were similarly injected with saline solution. Rats were sacrificed 4weeks after injections. Masticatory muscles examination and microcomputed tomography (microCT) were performed. A significant difference of weight was found between the 2 groups at weeks 2, 3 and 4 (p<0.05). Atrophy of the right masseter and temporal muscles was observed in all BTX rats. MicroCT analysis showed significant bone loss in the right alveolar and condylar areas in BTX rats. Decrease in bone volume reached −20% for right alveolar bone and −35% for right condylar bone. A hypertrophic bone metaplasia at the digastric muscle enthesis was found on every right hemimandible in the BTX group and none in the CTRL group. BTX injection in masticatory muscles leads to a significant and major mandible bone loss. These alterations can represent a risk factor for fractures in human. The occurrence of a hypertrophic bone metaplasia at the Mus Digastricus enthesis may constitute an etiological factor for tori.

Treatment of compensatory hyperhidrosis after sympathectomy with botulinum toxin and anticholinergics.

Compensatory hyperhidrosis (CH) is the most common adverse complication of sympathectomy. It often has a major negative impact on life quality. No efficient treatment of CH is available. We report nine cases of CH after sympathectomy, which were treated with botulinum toxin A/B (BTX) and anticholinergics. The patients responded to a dermatology life quality index (DLQI) questionnaire before injections with BTX and 3weeks after treatment. At the follow-up visit, the participants also ranked the effect of the treatment on a five-grade scale. Three patients had residual sweating after BTX treatment, and received additional anticholinergics at the follow-up visit. Those subjects eventually had a third evaluation with the DLQI. The DLQI score was, on average, 16.4 before treatment and decreased to 4.8 after BTX injections. Eight out of nine patients were satisfied with the treatment. The average DLQI score decreased to 2.2 when the patients with residual sweating (n=3) received additional anticholinergics. Adverse events from BTX were mild and temporary, but dry mouth was substantial in one patient using anticholinergics. A combination of BTX A/B and anticholinergics alleviated the hyperhidrosis with minor side-effects. We consider this treatment safe, effective, and well tolerated.

MP76-04 PREDICTING WHICH PATIENTS WILL ONLY UNDERGO A SINGLE ONABOTULINUMTOXINA INJECTION: RESULTS FROM A TERTIARY REFERRAL CENTER

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-neurogenic Voiding Dysfunction1 Apr 2014MP76-04 PREDICTING WHICH PATIENTS WILL ONLY UNDERGO A SINGLE ONABOTULINUMTOXINA INJECTION: RESULTS FROM A TERTIARY REFERRAL CENTER Rebecca Lavelle, Burhan Coskun, and Gary E. Lemack Rebecca LavelleRebecca Lavelle More articles by this author , Burhan CoskunBurhan Coskun More articles by this author , and Gary E. LemackGary E. Lemack More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2397AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES OnabotulinumtoxinA (BTX) detrusor injection is an effective treatment for patients with neurogenic detrusor overactivity (NDO) and overactive bladder (OAB). Still, not all patients request repeat injections. We sought to identify patient characteristics associated with the decision to not request repeat BTX injections. METHODS We analyzed demographic (including questionnaire) and urodynamic (UDS) data from an IRB approved database of patients with neurogenic bladder conditions and OAB. Patients were excluded for: prior inclusion in a BTX trial (n=6), deceased from unrelated causes (n=2), initial injection within the last 9 months (n=27). RESULTS From January 2009 through August 2013, 109 unique patients underwent a total of 206 injections. All patients were invited to call for repeat injection any time three months after the original injection. Of the 74 patients (59 NDO, 15 OAB) who met inclusion criteria, 56 (76%) underwent or have scheduled repeat injections (RI), and 18 (24%) had a single injection only (SI). In the SI group, the indications for injection were OAB (44.4%) and NDO (55.6%), and the corresponding values in the RI group were OAB (12.5%) and NDO (87.5%), (p=0.0065). Of the SI patients with OAB, 4 of 8 patients had secondary diagnoses: 3 with prior prostate cancer therapy, 1 with Painful Bladder Syndrome (PBS). Of the RI patients with OAB, 3 of 7 had secondary diagnoses (prior urologic surgery or pelvic radiation). The most common reasons for a SI were insufficient response (66.7%) or dissatisfaction due to de novo clean intermittent catheterization (CIC) (16.7%). Of the 12 with insufficient response, 6 required other intervention (catheterization, augmentation, cystectomy). De novo CIC was required in 27.8% of those in the SI group and 3.6% in the RI group (p=0.0079). Baseline UDS and questionnaire data, shown in Table 1, did not differ between groups. CONCLUSIONS In our experience, patients with refractory complex forms of OAB were more likely to have a SI only. Insufficient response and de novo CIC were the most common reasons for SI. Neither UDS nor questionnaire data were predictive of a single BTX injection. Table 1. Patient Characteristics and Urodynamic Data in BTX Single Injection (SI) vs. Repeat Injection (RI) SI (n=18) RI (n=56) P value Age, yrs, mean ± SD 56.5 ± 14 59.9 ± 18.5 0.42 Gender 0.82 Male, n (%) 5 (27.8%) 15 (26.8%) Female, n (%) 13 (72.2%) 41 (73.2%) Diagnosis 0.0065 NDO, n (%) 10 (55.6%) 49 (87.5%) OAB, n (%) 8 (44.4%) 7 (12.5%) De novo CIC, n (%) 5 (27.8%) 2 (3.6%) 0.0079 % Detrusor Overactivity 68.8% 77.3% 0.52 MCC, mL, mean ± SD 215 ± 173.8 238.5 ± 162.9 0.76 Reflex volume, mL, mean ± SD 136.7 ± 96.7 175 ± 160.6 0.77 pdetMax, cmH2O, mean ± SD 57.5 ± 28.5 52 ± 35.9 0.68 OABq-SF, Score (6-36), mean ± SD 21.1 ± 9.8 24.9 ± 8.4 0.25 PGIS, Score (1-4), mean ± SD 3.6 ± 0.7 3.5 ± 0.7 0.45 © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e883 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Rebecca Lavelle More articles by this author Burhan Coskun More articles by this author Gary E. Lemack More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Is an Instrumented Spasticity Assessment an Improvement Over Clinical Spasticity Scales in Assessing and Predicting the Response to Integrated Botulinum Toxin Type A Treatment in Children With Cerebral Palsy?

ObjectiveTo compare responsiveness and predictive ability of clinical and instrumented spasticity assessments after botulinum toxin type A (BTX) treatment combined with casting in the medial hamstrings (MEHs) in children with spastic cerebral palsy (CP). DesignProspective cohort study. SettingHospital. ParticipantsConsecutive sample of children (N=31; 40 MEH muscles) with CP requiring BTX injections. InterventionClinical and instrumented spasticity assessments before and on average ± SD 53±14 days after BTX. Main Outcome MeasuresClinical spasticity scales included the Modified Ashworth Scale and the Modified Tardieu Scale. The instrumented spasticity assessment integrated biomechanical (position and torque) and electrophysiological (surface electromyography) signals during manually performed low- and high-velocity passive stretches of the MEHs. Signals were compared between both stretch velocities and were examined pre- and post-BTX. Responsiveness of clinical and instrumented assessments was compared by percentage exact agreement. Prediction ability was assessed with a logistic regression and the area under the receiver operating characteristic (ROC) curves of the baseline parameters of responders versus nonresponders. ResultsBoth clinical and instrumented parameters improved post-BTX (P≤.005); however, they showed a low percentage exact agreement. The baseline Modified Tardieu Scale was the only clinical scale predictive for response (area under the ROC curve=0.7). For the instrumented assessment, baseline values of root mean square (RMS) electromyography and torque were better predictors for a positive response (area under the ROC curve=.82). Baseline RMS electromyography remained an important predictor in the logistic regression. ConclusionsThe instrumented spasticity assessment showed higher responsiveness than the clinical scales. The amount of RMS electromyography is considered a promising parameter to predict treatment response.

The Mayo Clinic Arizona Spasmodic Dysphonia Experience: 24 Years and 686 Patients

Objectives: 1) Outline onabotulinumtoxinA (onaBTX-A) injection dose and frequency trends in adductor spasmodic dysphonia (AdSD) patients. 2) Assess correlations between onaBTX-A injection dose, duration of breathiness, time to therapeutic onset, percent maximal benefit obtained, and duration of benefit. Methods: Retrospective chart review. Setting: Tertiary academic care center. Subjects and Methods: 686 patients with spasmodic dysphonia (SD) were treated with 6345 BTX injections between 1989 and 2013. This included 630 AdSD and 56 AbSD patients further subdivided into subgroups based on presence of vocal tremor (VT) and injection laterality. Injection frequency, dosing, laterality, and background demographic data were recorded in addition to subjective onaBTX-A injection responses. Results: AdSD patients’ symptom onset and injections began at an older age than AbSD patients (52.5; 60.6 years vs. 43.7; 50.0 years respectively; P = 0.0008) and had VT more frequently ( P= 0.0012). For the 380 AdSD patients (+/- VT) receiving over six injections, the average total onaBTX-A dose was 5.0 units, which remained stable up to 15 years (year 15 dose mean= 5.29, std dev= 5.07). Using Pearson’s correlation coefficients, there was no significant positive or negative correlation between onaBTX-A dose and percent maximal benefit (p=0.760), duration of breathiness ( P = 0.618), dysphagia duration ( P = 0.142), benefit duration ( P = 3622), or time to therapeutic onset ( P = 0.618). Conclusions: Spasmodic dysphonia is effectively treated according to patient subjective response; however, more refined longitudinal analysis is needed to show if any objective correlation between injection dose and outcomes are present. Treatment methods and outcomes as described should aid others in developing best practice patterns.

Botulinum Toxin A for Oral Cavity Cancer Patients: In Microsurgical Patients BTX Injections in Major Salivary Glands Temporarily Reduce Salivary Production and the Risk of Local Complications Related to Saliva Stagnation

In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection) and to reconstruct the affected area by means of free flaps. The saliva stagnation in the post-operative period is a risk factor with regard to local complications. Minor complications related to saliva stagnation (such as tissue maceration and wound dehiscence) could become major complications compromising the surgery or the reconstructive outcome. In fact the formation of oro-cutaneous fistula may cause infection, failure of the free flap, or the patient’s death with carotid blow-out syndrome. Botulinum injections in the major salivary glands, four days before surgery, temporarily reduces salivation during the healing stage and thus could reduce the incidence of saliva-related complications. Forty three patients with oral cancer were treated with botulinum toxin A. The saliva quantitative measurement and the sialoscintigraphy were performed before and after infiltrations of botulinum toxin in the major salivary glands. In all cases there was a considerable, but temporary, reduction of salivary secretion. A lower rate of local complications was observed in the post-operative period. The salivary production returned to normal within two months, with minimal side effects and discomfort for the patients. The temporary inhibition of salivary secretion in the post-operative period could enable a reduction in saliva-related local complications, in the incidence of oro-cutaneous fistulas, and improve the outcome of the surgery as well as the quality of residual life in these patients.

Botulinum toxin type A-induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder

Botulinum toxin type A (BTX) is a potent neurotoxin, which in recent years has been effectively applied in experimental treatments of many neurogenic disorders of the urinary bladder. BTX is a selective, presynaptically-acting blocking agent of acetylcholine release from nerve terminals what, in turn, leads to the cessation of somatic motor and/or parasympathetic transmission. However, application of this toxin in urological practice is still in the developmental stages and the full mechanism of its action remain elusive. Thus, the present study was aimed at investigating the neurochemical characterization of dorsal root ganglion (DRG) neurons supplying the porcine urinary bladder after BTX treatment. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall in six juvenile female pigs and three weeks later, intramural bladder injections of BTX (100 IU per animal) were carried out in all the animals. After a week, DRG from L1 to Cql were harvested from the pigs and neurochemical characterization of FB+ neurons was performed using double- labeling immunofluorescence technique on 10-microm-thick cryostat sections. BTX injections led to a significant decrease in the number of FB+ neurons containing substance P (SP), calcitonin gene-related peptide (CGRP), calbindin (CB), somatostatin (SOM) and neuronal nitric oxide synthase (nNOS) when compared with that found in the healthy animals (19% vs. 45%, 18% vs. 36%, 0.6% vs. 3%, 0.4 vs. 4% and 0.1% vs. 6%, respectively) These data demonstrated that BTX changed the chemical coding of bladder sensory neurons, and therefore this drug should be taken into consideration when it planning experimental therapy of selected neurogenic bladder disorders.

Effect of Botulinum Toxin Therapy on the Sensorimotor Feedback Loop in Cervical Dystonia (IN6-1.009)

Objective: To study the effects of botulinum toxin on intracortical inhibition and somatosensory organization. Background The cardinal manifestations of dystonia may be explained by excessive gain through a sensorimotor loop. Expanded overlapped receptor fields induce sustained, uncontrolled motor activity with co-contraction and overflow movements. There is a decreased cortical and spinal inhibition in dystonic patients. Increased motor and supplemental cortical excitability was demonstrated in trans-cranial magnetic stimulation studies. Somatosensory evoked potential studies have shown an increased sensory cortical excitability. Our group recently found synchronous (Coherent) neuronal oscillations to be higher in Epilepsy patients compared to controls which correlated with epileptogenic focus. The current study evaluated the alteration of neuroplasticity in dystonic patients treated with botulinum treatment (BTx). Design/Methods: Six patients with cervical dystonia were studied using MEG. Two MEG scans were obtained, one just prior to the Btx injections, and the second scan when patient felt maximum relief (at approximately 4 weeks). Tsui Torticollis Rating Scale (TTRS) was employed to evaluate treatment response. A whole head Neuromagnetometer (148 channel, Magnus 2500 system) was used. Spontaneous resting brain activity for Coherence (C) analysis was obtained. Somatosensory evoked field scans (SES) were obtained through sensory evoked responses to pressure tapping of the second digit. Results: All patients achieved significant improvement which corresponds to a reduction in their TTRS. Average pretreatment coherent rest values of 0.42 + 0.09 decreased to 0.38 + 0.07 after Btx. These were much higher than the resting state coherent values of normal controls of 0.17 +/-0.09 (p Conclusions: 1. Reduced Coherence values for resting brain activity indicate Btx restores intra-cortical inhibition. 2. Btx induced SES alteration modifies somatosensory processing contributing to the near normalization of dystonic posturing. Supported by: Research support from Allergan for the project : Effects of Botulinum on the Afferent Input Modulation of Neuronal Circuits Involved in Cervical Dystonia. Disclosure: Dr. Sripathi has nothing to disclose. Dr. Grover has nothing to disclose. Dr. Sidiropoulos has nothing to disclose. Dr. Bowyer has nothing to disclose.

Audit of Safety of Intramuscular Botulinum Toxin Injections among Patients Receiving Warfarin Anticoagulation Therapy

Abstract Background Botulinum toxin (BTX) intramuscular injections are an effective treatment for spasticity in acquired brain injury. Despite use since the 1980s, issues concerning technique, dose and long-term side-effects remain unresolved. For example, the safety of BTX in warfarinised patients is unclear. There are two studies reporting the risk of intramuscular injections in patients receiving anticoagulant therapy with regard to possible local haematoma formation. There is no advice on this subject in the manufacturers’ summary of product characteristics for the original brand of warfarin, Dysport, BOTOX, Xeomin or in the British National Formulary. Aim To assess the safety of BTX injections in patients receiving oral anticoagulation. Design Prospective audit of safe practice. Setting Outpatient setting in a rehabilitation centre. Population Adult population affected with spasticity with acquired brain injury and receiving concurrent warfarin anticoagulant therapy. Methods Fourteen patients who were receiving anticoagulant therapy were given regular BTX (number of injection cycles or total mean no of injections each). Patients gave written informed consent before the injections. Injection technique did not differ from that used for un-anticoagulated patients. Patients were assessed by the injector for obvious haemorrhage in the first 15 minutes after the injection resulting in swelling, bruising, tenderness or haematoma. Patients were asked to watch for appearance of local reactions like swelling, bruising or haematoma and pain in the first week. Results There were no clinically detectable local complications after intramuscular injections and no major or minor bleeding episodes after BTX injections. Conclusion In our group, BTX injections were administered intramuscularly to patients who were receiving anticoagulant therapy without significant risk of local bleeding. However, injections must be used with caution in patients with an INR above the therapeutic range. Clinical rehabilitation impact BTX can be safely given in patients on anticoagulation therapy with safety checks in place.

Reply: Does Clostridium botulinum neurotoxin A exhibit molecular mimicry with thyroid autoantigens and cause thyroid complications in predisposed persons?

We thank Atassi and Deitiker [1] for the opportunity to give some clarifications. Their references 2 and 3 (the latter published after our paper) report epitopes targeted by protective antibodies against Clostridium botulinum neurotoxin A (Btx), different from our epitopes. However, because our patient was not immunoresistant to 10-year duration of Btx injections, chances are she had non-neutralizing Btx-antibodies. Contiguity of four or more identical aminoacids is not necessary for cross-reaction, and the molecular mimicry hypothesis cannot be rejected on this basis. For example, the peptide YVLEGTLTA (aa 165–173 of Borrelia burgdorferi OspA) experimentally cross-reacts with YVIEGTSKQ (aa 332–340 of human LFA-1) [2]. We agree that only experimental evidence is definitive, but our patient did not return subsequently making impossible further tests with synthetic peptides, other Btx formulations or placebo. We could not find data on the concentration of flagellins in Dysport , nor about possible contamination of other Btx products by flagellins. It is therefore impossible to say whether administration of a different Btx product would make a difference. However, it seems unlikely that flagellins in Dysport can trigger thyroid autoimmunity. Available data [3] suggest that they interact with TLR-5, perhaps acting as adjuvants but not causing anti-flagellin response. Moreover, while many researches detected Btx antibodies, none reported flagellin antibodies following Btx injections. Statistical significance of homologies concerning short peptides not always correlates to biologic significance. For example, an E value of 23 (largely statistically insignificant) is obtained when comparing the aforementioned Borrelia epitope YVLEGTLTA against itself. Although our proposed antigen mimicry needs experimental testing, it cannot be ruled out based on statistics. We never mentioned discontinuous epitopes because we believe that, based on our analysis, they are not involved in this case. Concerning data in our Fig. 1 (left inset), in principle it is correct that the more are the data the more accurate and reliable are correlations. The graphic, based on the only three values available, is meant to show a consistent trend to decrease of TSHR-Ab across months after Btx injection. However, we could not ignore the resulting perfectly linear statistically significant inverse relationship. Finally, the mechanism of antigen presentation, detailed in literature [4], explains HLA-related predisposition to specific autoimmune diseases through molecular mimicry. Peptide binding E. Gregoric Department of Nuclear Medicine, Hospital Izola, Izola, Slovenia