Botulinum Toxin A Application Research Articles

Sonographic guide for botulinum toxin injections for chronic migraine headache: EURO-MUSCULUS/USPRM approach

Application of botulinum toxin A (BoNT-A) into the muscles of the head and neck area has become a widespread and reliable treatment modality for chronic migraine. The mechanism of action for BoNT-A is the inhibition of acetylcholine and local nociceptive peptide release at the terminal nerve endings. Cranial sutures have the highest concentration of nociceptive structures; therefore BoNT-A injection into the suture lines - as opposed to head and neck muscles - has been proposed for the treatment of chronic migraine. Nerve endings in sutures rapidly absorb BoNT-A and transfer it across the afferent nerve fibers in dura mater via orthodromic and antidromic transmission. In this article, ultrasound-guided BoNT-A application around the cranial sutures will be illustrated. It is noteworthy that suture injections would be safer and more efficient when applied with such guidance.

The Place of Botulinum Toxin in Spastic Hemiplegic Shoulder Pain after Stroke: A Scoping Review

Stroke is a common pathology worldwide, with an age-standardized global rate of new strokes of 150.5 per 100,000 population in 2017. Stroke causes upper motor neuron impairment leading to a spectrum of muscle weakness around the shoulder joint, changes in muscle tone, and subsequent soft tissue changes. Hemiplegic shoulder pain (HSP) is the most common pain condition in stroke patients and one of the four most common medical complications after stroke. The importance of the appropriate positioning and handling of the hemiplegic shoulder for prevention of HSP is therefore of high clinical relevance. Nevertheless, HSP remains a frequent and disabling problem after stroke, with a 1-year prevalence rate up to 39%. Furthermore, the severity of the motor impairment is one of the most important identified risk factors for HSP in literature. Spasticity is one of these motor impairments that is likely to be modifiable. After ruling out or treating other shoulder pathologies, spasticity must be assessed and treated because it could lead to a cascade of unwanted complications, including spastic HSP. In clinical practice, Botulinum toxin A (BTA) is regarded as the first-choice treatment of focal spasticity in the upper limb, as it gives the opportunity to target specifically selected muscles. It thereby provides the possibility of a unique patient tailored focal and reversible treatment for post stroke spasticity. This scoping review aims to summarize the current evidence of BTA treatment for spastic HSP. First, the clinical manifestation and outcome measures of spastic HSP will be addressed, and second the current evidence of BTA treatment of spastic HSP will be reviewed. We also go in-depth into the elements of BTA application that may optimize the therapeutic effect of BTA. Finally, future considerations for the use of BTA for spastic HSP in clinical practice and research settings will be discussed.

Botulinum toxin-A in the treatment of upper facial wrinkles: efficacy comparison of different formulations

Objective: It is suggested that different formulations of botulinum toxin-A (BoNT-A) used for the same indication might be a factor affecting patient satisfaction. This study aimed to assess patient satisfaction levels in treating upper facial wrinkles (UFW) using various BoNT-A formulations and their association with age and gender. Materials and Methods: This retrospective study included 600 UFW patients treated with different formulations of BoNT-A. The BoNT-A formulations included three different groups: onaBoNT-A (ONA, n:200), aboBoNT-A (ABO, n:200), and praBoNT-A (PRA, n:200).In the patient files or records, satisfaction levels from the BoNT-A application were scored as follows: 1: not satisfied, 2: slightly satisfied, 3: satisfied, 4: very satisfied, 5: completely satisfied. Results: The mean patient satisfaction scores were similar in the ONA and ABO groups, but higher in the PRA group (4.4±0.5 vs. 4.3±0.6 vs. 4.0±0.9, P <0.001, respectively). The mean satisfaction score of the patients aged 18-30 and those aged >60 were lower than the other age groups. Among all patients in the 41-50 age range, the patient satisfaction score was higher in the ONA group than the ABO and PRA group. In all female patients, the mean satisfaction score was lower in the PRA group compared to the ONA and ABO groups (P <0.001), Conclusions: While various BoNT-A formulations are generally associated with high patient satisfaction in the treatment of UFW, this can vary depending on age ranges and gender. Evaluating patient-related factors such as age and gender can contribute to the treatment planning for UFW and enhancing treatment adherence.

Long-term efficacy and safety of repeated botulinum toxin a applications based on function and anesthesia type in children with cerebral palsy

PurposeThis study evaluates the motor development of patients undergoing three or more repeated Botulinum toxin A (BoNT-A) applications in a tertiary pediatric hospital as well as the safety of three different types of anesthesia. MethodsSeventy-five children who underwent BoNT-A applications at least three consecutive times at six-month intervals and a total of 320 procedures were examined. Gross Motor Function Classification System (GMFCS) was employed in motor development evaluation. The three anesthesia methods (sedation analgesia, anesthesia with larengeal mask [LMA] and inhalation mask) were compared in terms of sedation, procedure, recovery, and total operation room time. ResultsFollowing the procedures, significant motor development was observed in 60 (80%) patients. In sedation analgesia group during the first three procedures, the recovery time was seen to be significantly shorter, while there was no difference between the anesthesia methods of any procedures following the fourth. Regardless of the type of anesthesia, the recovery times of those having undergone six or more procedures were longer than those with less than six procedures. ConclusionsAs repeated BoNT-A application provides motor step progress, it can be applied safely and effectively under anesthesia. Sedation analgesia provides an easier recovery compared to LMA and mask only within the first three applications. However, recovery time increases with four or more repeated applications, specifically increasing as the number of applications increases. Level of evidenceIII.

Cortical somatosensory processing after botulinum toxin therapy in post-stroke spasticity.

In dystonic and spastic movement disorders, abnormalities of motor control and somatosensory processing as well as cortical modulations associated with clinical improvement after botulinum toxin A (BoNT-A) treatment have been reported, but electrophysiological evidence remains controversial. In the present observational study, we aimed to uncover central correlates of post-stroke spasticity (PSS) and BoNT-A-related changes in the sensorimotor cortex by investigating the cortical components of somatosensory evoked potentials (SEPs). Thirty-one chronic stroke patients with PSS of the upper limb were treated with BoNT-A application into the affected muscles and physiotherapy. Clinical and electrophysiological evaluations were performed just before BoNT-A application (W0), then 4 weeks (W4) and 11 weeks (W11) later. PSS was evaluated with the modified Ashworth scale (MAS). Median nerve SEPs were examined in both upper limbs with subsequent statistical analysis of the peak-to-peak amplitudes of precentral P22/N30 and postcentral N20/P23 components. At baseline (W0), postcentral SEPs were significantly lower over the affected cortex. At follow up, cortical SEPs did not show any significant changes attributable to BoNT-A and/or physiotherapy, despite clear clinical improvement. Our results imply that conventional SEPs are of limited value in evaluating cortical changes after BoNT-A treatment and further studies are needed to elucidate its central actions.

Evaluation of Changes in Depression Levels of Bruxism Patients Treated With Botulinum Toxin-A

Aim: Bruxism is defined as the involuntary recurrent masticatory muscle activity characterized by gnashing, grinding, clenching of teeth, and/or pushing the mandible. Factors creating its etiology are peripheral (morphological) or central (physiopathological and physiological), and exogenous. Recently, among physiological factors, depression and bruxism were considered to be related. A definitive treatment method does not exist for bruxism; however, botulinum toxin-A (BT-A) application is an up-to-date and effective way of treatment. The present study is aimed to evaluate the levels of depression in bruxism patients treated with BT-A application. Materials and Methods: A total of 25 individuals (23 females and 2 males) who were diagnosed as bruxism patients were included in the study. 25 U of BT-A for each masseter muscle was injected into the patients. Patients were prospectively observed for a possible change in depression levels by using Beck’s Depression Inventory. The inventory was implemented before and six months after the BT-A application. Depression levels before and six months after the injection were compared. A paired t-test was used to compare “before” and “after” treatment values. One-way analysis of variance and post-hoc Tukey tests were used to evaluate the change in Beck’s Depression Inventory scores according to age groups. Results: The mean total score was 7.80 ± 8.10 before the treatment and 7.16 ± 6.52 six months after the treatment. The decrease in the mean score was not statistically significant ( P > .05). Conclusion: In conclusion, despite the decrease in the mean Beck’s Depression Inventory scores, a statistically significant decrease in the depression levels of patients was not observed.

Impact of botulinum toxin-A on corneal curvature assessed with Scheimpflug and Placido systems

To evaluate the effect of eyelid spasm treatment with botulinum toxin-A (BTX-A) on corneal curvature assessed with Scheimpflug (Pentacam) and Placido (Atlas) systems. Federal University of São Paulo, São Paulo, Brazil. Prospective interventional case series. Patients with hemifacial spasm were evaluated. Steep keratometry (K) and corneal astigmatism (magnitudes and treatment-induced astigmatism) obtained with the Placido and Scheimpflug systems were evaluated before BTX-A application and after 15days and 2, 3, and 4months. The study evaluated 48 eyes (24 affected and 24 normal contralateral eyes) of 24patients. The mean steep K and astigmatism values obtained with the Placido system on the affected side beforetreatment were 46.91 diopters (D)±3.57 (SD) and 2.63±2.46 D, respectively. A significant decrease in steep K (45.14±1.20 D) and astigmatism (1.01±0.58 D) was observed 2months (P=.003 and P=.0004, respectively) and 3months (45.64±1.77 D and 1.36±1.31 D, respectively) (P=.03 and P=.01, respectively) after treatment. The Scheimpflug system did not show significant changes in steep K measurements during the 4-month period. The mean astigmatism in the affected eye before treatment was 1.27±0.88 D. A significant reduction was observed at 15days (1.16±1.16 D) and at 4months (0.91±0.59 D) (P=.02 and P=.03, respectively). The Placido system was more sensitive in detecting a temporary reduction in corneal curvature after eyelid-spasm treatment. None of the authors has a financial or proprietary interest in any material ormethod mentioned.

Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects

ObjectiveTo report on the experience of injections of botulinum toxin A (BTA) in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS) level V. MethodsThis was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations), in which the basic aim was to look for adverse effects. ResultsThe mean number of application sessions per patient was three, and the mean age at the time of each injection was 4+6 years (range: 1.6–13 years). The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193U and the mean dose per weight was 12.5U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month. ConclusionThe absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia.

Tratamento focal da espasticidade com toxina botulínica A na paralisia cerebral GMFCS nível V – Avaliação de efeitos adversos

Objectiveto report on the experience of injections of botulinum toxin A (BTA) in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS) level V. Methodsthis was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations), in which the basic aim was to look for adverse effects. Resultsthe mean number of application sessions per patient was three, and the mean age at the time of each injection was 4+6 years (range: 1.6 to 13 years). The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow‐up of one month. Conclusionthe absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia.

Comment to: Chemical components separation with botulinum toxin A: a novel technique to improve primary fascial closure rates of the open abdomen by Zielinski et al.

We read with great interest the article by Dr. Zielinski et al. [1]. The authors presented a retrospective review of their experience with botulinum toxin A (BTA) (Botox , Allergan, Inc. Irvine, CA 92612) application into the lateral abdominal wall musculature of open abdomen (OA) patients, in order to describe the BTA injection technique and to determine its effects on the abdominal wall after OA, which is named by the authors ‘‘chemical components separation technique.’’ A total of 18 patients were included. Indications for OA management included bowel viability (39 %), shock (33 %), feculent contamination (17 %), and loss of abdominal domain (6 %). A median of 3 serial abdominal explorations (1–8) after the initial OA management was required. Temporary abdominal closures with negative pressure dressings were applied. A primary fascial closure rate of 83 %, partial fascial closure rate of 6 %, and planned ventral hernia rate of 11 % are reported. The authors reported a BTA injection within 24 h of the initial OA procedure in 50 % of the cases, achieving an 89 % primary fascial closure rate, and 11 % partial fascial closure rate of these patients. An overall 67 % complication rate was found, with fascial dehiscence in 11 %. The clinical effect of botulinum toxin has been demonstrated as early as day 3 after intramuscular injection with a maximum effect at 2 weeks [2]. In a prospective study of twelve patients with abdominal wall hernia secondary to OA management, the maximal effect of BTA (Dysport, IPSEN, France) was observed at 3 weeks after injection. A significant reduction in the transverse hernia defect diameter was achieved [3]. The high overall primary fascial closure rate in patients with BTA injection within 24 h of the initial OA procedure achieved by Dr. Zielinski et al. [1] is particularly interesting. We would like to ask Dr. Zielinski et al., at what time were the remaining patients injected with BTA and the time at which abdominal closure was performed. Dr. Zielinski et al. reported 6 injection sites on the abdominal wall: right/left subcostal; right/left anterior axillary; right/left lower quadrants. Injection of 16.6 units of the BTA solution for each of external oblique, internal oblique, and transverse muscles is performed at each of the 6 injection sites (50 units per injection site, total of 300 units). Our group reported BTA application at 10 sites: two sites at the middle axillary line between costal margin and iliac crest level, and three sites between anterior axillary line and middle clavicular line between costal margin and iliac crest level, with similar sites on the opposite side, for a total of 50 units per injection site dosage [3]. A considerable range of 20–75 % of surviving patients managed with OA will have the abdominal fascia closed prior to discharge, while the remaining patients may undergo abdominal wall reconstruction afterward [4]. With no doubt, BTA injection will constitute an important adjuvant to abdominal wall closure in patients under OA management, planned ventral hernia or large abdominal wall hernias. This comment refers to the article available at doi:10.1007/s10029-012-0995-1.

A close positive correlation between malodor and sweating as a marker for the treatment of axillary bromhidrosis with botulinum toxin A

Background: Botulinum toxin A (BTX-A) has been demonstrated to be only effective for some types of axillary bromhidrosis. It is necessary to explore the indications for BTX-A application. Methods: Sixty-seven consecutive outpatients with axillary bromhidrosis were recruited after informed content. Then, 50 U of BTX-A was injected intracutaneously into 20 different sites within each axilla. The follow-up was done every month and terminated when the malodor returned to the previous level. Results: Of 67 cases, 74.6% (50/67) had mild or moderate malodor, and 80.6% (54/67) experienced mild or moderate sweating. In 76.1% (51/67) of patients, there were a close correlation between malodor and sweating. After BTX-A injection, the malodor was eliminated in 73.1% (49/67) of patients. Logistic regression analysis revealed that the correlation between malodor and sweating differed significantly between the group that maintained no malodor after initial injection and the group that still exhibited malodor. Conclusion: BTX-A ameliorates malodor mainly by the inhibition of eccrine and apoeccrine sweating but no apocrine sweating. A close positive correlation between malodor and sweating is the indication for BTX-A treatment.

Preoperative botulinum toxin test injections before muscle lengthening in cerebral palsy

BackgroundMuscle weakening is a well-known side effect of muscle-tendon lengthening. Botulinum toxin A (BTX-A) weakens the muscle temporarily by blocking the neuromuscular junction. Hence application of the drug is a logical step to test whether weakness deteriorates function prior to an operation. In the present study, BTX-A application is used to test preoperatively whether the gait pattern depends on the strength of the tested muscle. Since 1999, instrumented gait analysis, including kinematic, kinetic, and dynamic electromyographic data, is routinely used to define the individual surgical program. MethodsIn our series of 110 consecutive patients with cerebral palsy (CP) considered for surgical muscle lengthening from 1999 to 2008, BTX-A was applied to identify patients at risk for functional deterioration. Gait analysis was repeated 6 weeks (maximum effect of BTX-A) and 12 weeks (follow-up) after the test injection to check for loss of joint control (excessive ankle dorsiflexion, knee flexion, increased anterior pelvic tilt). ResultsIn all, 20.9% (n = 23) showed deterioration in gait after preoperative BTX-A test injections (n = 112, two patients had two test trials) in all muscles considered for lengthening. As a consequence, their lengthening surgery was canceled. A total of 68 patients underwent surgery as planned, and in none of them did gait function deteriorate. These clinical data were compared to those of a historical group (n = 105) before this test, where 18% showed functional deterioration after surgery. The similar percentage of patients filtered out by the test suggests that there could be a context to the number of poor results in the historical group. ConclusionsWe conclude that preoperative BTX-A test injection is a reliable tool for filtering out patients with risk of deterioration after muscle lengthening surgery in patients with CP and can be helpful to avoid poor outcomes.

Prospective, Randomized, Double-Blind Study, Comparing Botulinum Toxins Type A Botox and Prosigne for Blepharospasm and Hemifacial Spasm Treatment

Botulinum toxin A (BTA) is considered an effective treatment of blepharospasm and hemifacial spasm, but there are few studies to permit a comparison of its different formulations. This prospective, randomized, double-blind study compared Prosigne, a BTA of Chinese origin, with Botox to establish safety, efficacy, and equivalence of doses between those 2 formulations in blepharospasm and hemifacial spasm treatment. Fifty-seven patients participated in this study: 21 blepharospasm (from whom 11 were treated with Botox; and 10, with Prosigne) and 36 hemifacial spasm patients (17 were treated with Botox; and 19, with Prosigne). All patients were similar in age, disease time span, number of previous shots, and time elapsed since the last BTA application. Pain and burning during the injection and the result of the treatment were similar in both groups. There were no systemic adverse events, and the local ones were observed with similar intensity and frequency for both groups. The mean effect time length was similar for both blepharospasm (11.3 weeks for both toxins) and hemifacial spasm patients (12.8 weeks for Botox and 12.9 weeks for Prosigne). In both blepharospasm groups, only the 36-Item Short-Form Health Survey emotional aspects domain showed improvement from baseline after 16 weeks. There were no differences between the 36-Item Short-Form Health Survey scores before and after the treatment of all hemifacial spasm patients. Therefore, it has been concluded that Botox and Prosigne have similar efficacy, safety, and tolerability profiles, so that a dose equivalence of 1:1 may be considered for blepharospasm and hemifacial spasm treatments.

A Prospective, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Type A Botulinum Toxins Botox and Prosigne in the Treatment of Cervical Dystonia

Botulinum toxin A (BTA) is considered an effective treatment of cervical dystonia. The aim of this prospective, randomized, double-blind study was to compare Botox and Prosigne, a BTA of Chinese origin, with a view to establish the safety, the efficacy, and the equivalence of doses of the 2 formulations in the treatment of cervical dystonia. Twenty-four patients were randomized to receive 300 U of Botox or Prosigne (12 patients in each group). The patients were assessed before the injection and after 4 and 16 weeks by the Toronto Western Spasmodic Torticollis Rating Scale and the Short-Form 36 for quality of life before and 16 weeks after the injection. All patients were comparable in age, time since onset, number of previous injections, and time since last BTA application. According to the Toronto Western Spasmodic Torticollis Rating Scale scores, the patients improved after injection and the scores increased after 16 weeks, without returning to baseline values. Both pain and burning during the injection and the treatment outcomes were similar in both groups. No systemic adverse events occurred, and the severity and frequency of local events were comparable in both groups. Average duration of effect was similar in both groups (11 weeks). The quality-of-life evaluations before and after the injections were comparable in both groups. Social aspects, pain, and vitality improved after 16 weeks in both groups. In conclusion, Botox and Prosigne were determined to have equivalent efficacy, safety, and tolerability profiles and dose equivalence for cervical dystonia treatment is 1:1.

Electromotive drug administration: a novel method for the treatment of overactive bladder with botulinum toxin a

Purpose To compare the results of cystoscopic intradetrusor injection of Botulinum Toxin A (BTX-A) with Electromotive Drug Administration(EMDA) as a minimally less invasive method and evaluate the effects of these two treatment modalities on incontinence and urodynamic parameters. Material and methods This study is a randomized controlled trial that approved by ethical committee. We selected 20 eligible children with overactive bladder (refractory to CIC and anticholinergic medications) divided into two equal groups. Group I, received the BTX-A by EMDA. Following insertion of special catheter containing a spiral silver electrode, the bladder was drained with sterile water. The preferred instillation volume based on estimated cystometeric bladder capacity results in a spherical bladder configuration. Two electrode pads were placed at paraumbilical region using contact electrode gel. The current generator which connected to the electrodes produced a pulsed direct current with a frequency of 2,500 Hz. BTX-A was administered (10U/kg) to the maximum designated current intensity (15 mA) in 15 minutes.Group II, received conventional cystoscopic BTX-A injection under general anesthesia. Clinical and urodynamic assessments were performed before and after the procedure in both groups. Results Detailed results will be reported in our presentation. According to our data it seems that using BTX-A by EMDA, improved the urinary incontinence and urodynamic parameters with higher therapeutic duration, disseminated infusion and deeper layer penetration with no invasive procedures in comparison with intaravesical injection. Conclusions To the best of our knowledge, this is the first report of BTX-A application for the treatment of pediatrics overactive bladder by EMDA as a simple and safe method, and compare its trapeutic effects with intradetrusor injection.

Predicting mobility gains among children with cerebral palsy after application of botulinum toxin A

Background: Botulinum toxin A (BTA) is commonly used to treat children with cerebral palsy (CP). However, the variables measured before BTA application and associated with motor function and independent mobility, known as predictors of functional outcomes, have not been well defined. Objective: To identify clinical predictors of gains in functional motor skills and independence of mobility among children with CP, three and six months after BTA application. Methods: This was a convenience sample of children with spastic CP (n=35). Measurements of quantitative gains in motor skills and independence of mobility were taken three and six months after BTA application. These outcomes were observed through repeated applications of two functional tests: GMFM (Gross Motor Function Measure) and PEDI (Pediatric Evaluation of Disability Inventory). These tests evaluated gross motor function while sitting or standing and during transitions between these postures, and also during dynamic activities such as walking, running and jumping, along with the children's independence in mobility tasks. The independent variables included the children's characteristics such as age, severity, topographic diagnosis, neuromuscular-skeletal parameters (range of motion and spasticity), gait quality and performance in the functional tests before BTA. Results: Four predictive models were developed (R 2 between 0.58 and 0.83; p<0.05) through the use of CART analysis: two at three months and two at six months after BTA application. The results indicated that children with better gait quality, smaller repertoire of functional motor skills, less independence of locomotion and age below four years and six months before BTA presented greater gains in motor skills and independence in mobility. Conclusion: The results identified significant clinical parameters that can predict functional outcomes of BTA applications among children with CP.