Doses Of Botulinum Toxin Type Research Articles

Low‐Dose Botulinum Toxin Type A for the Treatment of Refractory Piriformis Syndrome

To evaluate the efficacy of a single, low-dose injection of botulinum toxin type A in relieving pain in Korean patients with piriformis syndrome resistant to conventional therapy, and to assess the drug's influence on these patients' quality of life. Prospective, single-site, open-label trial. Rehabilitation medicine clinic in Seoul, Korea. Twenty-nine patients with a confirmed diagnosis of chronic piriformis syndrome and 82 age- and sex-matched healthy subjects were enrolled from April 1, 2003-February 28, 2004. Intervention. In 20 of the patients, botulinum toxin type A 150 U was injected using computed tomographic guidance into the affected unilateral piriformis muscle. The other nine patients served as active controls and received an injection of dexamethasone 5 mg and 1% lidocaine. The healthy subjects did not receive any injection. The patients' pain at baseline and at 4, 8, and 12 weeks after treatment was rated by using a numeric rating scale. Health-related quality of life was assessed by using the validated Korean version of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) at baseline and at 4 weeks of treatment. Healthy subjects also completed the SF-36 at baseline. Pain intensity scores were significantly lower at 4, 8, and 12 weeks after treatment than at baseline (p<0.0001). Baseline scores from the SF-36 subscales, including those for physical functioning (p<0.0001), role physical (p<0.0001), bodily pain (p<0.0001), general health (p<0.0001), vitality (p<0.0001), and social functioning (p<0.002), were significantly lower in the patients than in the healthy subjects. Four weeks after treatment, physical functioning (p=0.003), role physical (p=0.021), bodily pain (p=0.016), general health (p=0.013), vitality (p=0.031) and social functioning (p=0.035) improved significantly from baseline in the patients. However, at 4 weeks, patients in the active control group were withdrawn from the study because their pain did not improve, and continuation without further medical care was considered unethical. A low dose of botulinum toxin type A relieved pain and improved quality of life in patients with refractory piriformis syndrome.

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Reliability and Validity of the Incontinence Quality of Life Questionnaire in Patients With Neurogenic Urinary Incontinence

Schurch B, Denys P, Kozma CM, Reese PR, Slaton T, Barron R. Reliability and validity of the Incontinence Quality of Life questionnaire in patients with neurogenic urinary incontinence. Objective To assess the reliability, validity, responsiveness, and minimally important difference (MID) of the Incontinence Quality of Life (I-QOL) questionnaire in patients with urinary incontinence due to neurogenic detrusor overactivity. Design Randomized, double-blind, multicenter, placebo-controlled study. Setting Eight centers across Belgium, France, and Switzerland. Participants Patients with urinary incontinence due to neurogenic detrusor overactivity inadequately managed on oral anticholinergics. Fifty-nine patients (spinal cord injury, n=53; multiple sclerosis, n=6) were enrolled. Intervention Single dose of botulinum toxin type A (Botox) (200 or 300U) or placebo. Main Outcome Measures I-QOL questionnaire completed at screening and over a 24-week post-treatment period. Results The Cronbach α ranged from .79 to .93, indicating that I-QOL is a reliable measure of QOL in neurogenic urinary incontinence patients. No item had more than 5.1% missing or out of range values. With the exception of 2 items, questions showed acceptable item-scale correlation and scaling success results varied by domain. Post-treatment correlations indicated acceptable construct validity. The I-QOL was responsive to improvements in symptoms. MID values ranged from 4 to 11 points. Conclusions Results suggest that I-QOL is a reliable, valid, and responsive measure of incontinence-related QOL in neurogenic patients.

Low-dose subcutaneous injection of botulinum toxin type A for facial synkinesis and hyperlacrimation

To investigate the efficacy of low dose of botulinum toxin type A (BTX-A) for facial synkinesis and hyperlacrimation. Eleven patients suffering from facial synkinesis after Bell's palsy or facial nerve injury were treated with a low dose of BTX-A, 0.5-1.25 U per point into several points. One patient showing hyperlacrimation was also treated with BTX-A. The whole observational period was 43 months. On average, 5.76 U of BTX-A, which was lower than that of previous reports, was injected per treatment. In seven cases, synkinesis disappeared completely after three or fewer sessions of BTX-A injection. The mean interval between treatments was 14.5 weeks. Hyperlacrimation was completely suppressed after a single subcutaneous injection of BTX-A. Only mild subcutaneous hemorrhage was observed as adverse reactions. Facial synkinesis can be treated with a lower dose of BTX-A without relevant adverse reactions.

Skeletal Muscle Atrophy Induced by Intramuscular Repeated Dose of Botulinum Toxin Type A in Rats

Botulinum toxin type A was intramuscularly administered to Sprague–Dawley rats once a day for 28 days at doses of 1, 3, and 9 ng kg−1 day−1 to investigate the possibility of unanticipated toxicity of repeated dose. A dose-related decrease in body weight gain was noted and lasted throughout the 4-week recovery period. Paralytic gait was a common clinical sign observed in the animals dosed at ≥3 ng kg−1 day−1 and muscle atrophy at 9 ng kg−1 day−1. Decreased creatinine was monitored in both males and females treated at 9 ng kg−1 day−1. Microscopic examination of the quadriceps femoris muscle, the test article application site, confirmed the muscle atrophy with a decrease in myofiber diameter and an increase of myofiber nuclei and intermyofiber connective tissue. Although antibody against botulinum toxin type A was detected in the sera from both males and females at 9 ng kg−1 day−1, no immunogenicity-related changes or lesions were noted. In conclusion, no other side effects of the botulinum toxin type A injection except the decrease in body weight gain and the muscle atrophy at the administration site were noted in the 28-day intramuscular repeated dose study.

Utilisation de fortes doses de toxine botulique de type A chez l'enfant: intérêt et sécurité en pratique clinique

The purpose of this article is to examine the current state of administering high doses botulinum toxin type A for the treatment of chidhood spasticity, particularly Cerebral Palsy. The inter-relationship between the Cerebral Palsy neurological maturation and the early management is discussed, including identification of common gait patterns and the choice of target muscles for focal or multi focal spasticity management. High doses of botulinum toxin type A, when multilevel and integrated management approach is indicated, appear to be a safe, efficacious treatment for multi focal Cerebral Palsy spasticity. A review of literature guides the clinician about necessary adaptation of botulinum toxin doses and found no evidence that higher doses result in a increase of complications. Further studies would be interesting in order to evaluate long term safety and efficacy of this therapy in Cerebral Palsy.

A Series of Three Sequential, Randomized, Controlled Studies of Repeated Treatments With Botulinum Toxin Type A for Migraine Prophylaxis

We examined the effects of multiple treatments with low doses of botulinum toxin type A (BoNTA; BOTOX®, Allergan Inc., Irvine, CA) versus placebo for prophylaxis of episodic migraine. This was a series of 3 sequential, randomized, controlled studies of 418 patients with a history of 4 to 8 moderate to severe migraines per month. In study I, patients were randomized to treatment with placebo or BoNTA (7.5 U, 25 U, or 50 U) in predetermined fixed injection sites on the front and sides of the head only. In study II, patients continued to receive, or were randomized to, 2 consecutive treatments with 25 U or 50 U. In study III, patients were randomized to placebo or continuation of 25 U or 50 U. Injection cycles were each 4 months long. BoNTA and placebo produced comparable decreases from baseline in the frequency of migraines at each time point examined ( P ≥ .201). No consistent, statistically significant differences were observed for any efficacy variable. Adverse events were similar among the groups within each study. In these exploratory studies of episodic migraine patients, repeated injections of low doses of BoNTA into fixed frontal, temporal, and glabellar sites were not more effective than placebo. BoNTA was safe and well tolerated. Perspective Beneficial effects of BoNTA in the treatment of migraine have been reported, but positive results are not universal, possibly because the optimal patient population and regimen are not yet definitively established. This study explores the effects of multiple injections of low BoNTA doses into fixed sites for episodic migraine.

Prospective, Double-Blind, Randomized, Parallel-Group, Dose-Ranging Study of Botulinum Toxin Type A in Men with Glabellar Rhytids

The effective dose for treating glabellar lines with botulinum toxin type A in men has not been studied adequately. To compare the safety, efficacy, and duration of response of four doses of botulinum toxin type A on glabellar rhytids in men. Eighty men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (BOTOX, BOTOX Cosmetic, or Vistabel, Allergan, Inc., Irvine, CA, USA) in the glabellar area. Glabellar lines were assessed at rest and maximum frown by a trained observer at baseline, 2 and 4 weeks, and monthly thereafter. Patients provided self-evaluations at the same visits. Adverse events were monitored throughout. The 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose (duration, peak response rate, improvement from baseline). There was a dose-dependent increase in both the response rate at maximum frown and the duration of effect assessed by the trained observer. In addition, the participants reported a dose-dependent reduction in the ability to frown, improvement in their global assessment, and increased feelings of attractiveness, self-confidence, and satisfaction. The incidence of adverse events was not increased with higher doses. Male participants with glabellar rhytids benefit from starting doses of at least 40 U of botulinum toxin type A.

Effects of Botulinum Toxin Type A on Contouring of the Lower Face

Masseteric muscle hypertrophy is an uncommon dition represented as a swelling of the masseter muscle. Recent reports have demonstrated the successful use of botulinum in the treatment of masseteric hypertrophy. This study was a prospective trial to evaluate the effectiveness of botulinum toxin type A (Botox) in the treatment of masseteric muscle hypertrophy according to doses of 10, 20, and 30 U. Twenty-two patients were referred to the dermatologic clinic for the management of masseteric muscle hypertrophy. Ultrasonographic measurements of the thickness of the masseter muscle were performed, and clinical photographs were taken before treatment and 1, 2, 3, 4, 6, and 9 months after the treatment. RESULTS. The median values of percentage reduction of muscle mass were 10.3%, 16.5%, 23.7%, 24.7%, 21.6%, 16.5% in the 10 U group; 11.9%, 18.8%, 24.8%, 27.7%, 26.7%, and 21.8% in the 20 U group; and 12.0%, 19.4%, 25.0%, 27.8%, 37.8%, and 24.1% in the 30 U group. CONCLUSION. The adequate dose of botulinum toxin type A for treatment of masseteric muscle hypertrophy should be above 20 U. The effect of botulinum toxin type A is maintained for at least 9 months as the treatment of masseteric muscle hypertrophy.

Dose-Ranging Study of Botulinum Toxin Type A in the Treatment of Glabellar Rhytids in Females

To compare the efficacy, safety, and duration of effect of four doses of botulinum toxin type A in the treatment of glabellar rhytids in females. Double-blind, randomized, parallel-group, dose-ranging trial followed by an open-label extension. Private dermatologic clinic. Eighty female subjects with moderate to severe wrinkles at maximum frown entered the study. The first 40 subjects completing the double-blind phase entered the open-label extension. Random administration of 10, 20, 30, or 40 U botulinum toxin type A in divided doses. Open-label trial: 30 U botulinum toxin type A at the same sites in divided doses. Trained observer and subject assessments of wrinkle severity at maximum frown and repose using the Facial Wrinkle Scale (0 = none to 3 = severe), subject satisfaction, and adverse events. Follow-up monthly for up to 1 year postinjection. Relapse rates and responder rates revealed benefits lasting 3 to 6 months or longer. Objectively, 10 U of botulinum toxin type A was significantly less effective than 20, 30, or 40 U. The relapse rate at 4 months was significantly higher in the 10 U group (83%) versus 40, 30, or 20 U (28%, 30%, and 33%, respectively). Subject satisfaction was high in all groups. Duration of effect and response rates were sustained during the open-label extension. Adverse effects were mild and infrequent. Twenty to 40 U botulinum toxin type A doses were significantly more effective at reducing glabellar lines than 10 U. Most subjects experienced benefits for 3 to 4 months; some subjects demonstrated effect for up to 12 months.

Poster 239: Resource Utilization, Productivity, and Caregiver Burden Impact in a Trial of Repeated Doses of Botulinum Toxin Type A for the Treatment of Focal Upper-Limb Poststroke Spasticity: A Multicenter Open-Label Study

Poster 239: Resource Utilization, Productivity, and Caregiver Burden Impact in a Trial of Repeated Doses of Botulinum Toxin Type A for the Treatment of Focal Upper-Limb Poststroke Spasticity: A Multicenter Open-Label Study

BOTULINUM TOXIN TYPE A IS A SAFE AND EFFECTIVE TREATMENT FOR NEUROGENIC URINARY INCONTINENCE: RESULTS OF A SINGLE TREATMENT, RANDOMIZED, PLACEBO CONTROLLED 6-MONTH STUDY

We determined the safety and efficacy of each of 2 doses of botulinum toxin type A (BTX-A) (200 or 300 U BOTOX) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin. A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity (due to spinal cord injury in 53 and multiple sclerosis in 6) requiring clean intermittent self-catheterization were randomized to receive a single dose into the detrusor of BTX-A (200 U or 300 U) or placebo. Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks. Key urodynamic assessments (maximum cystometric capacity, reflex detrusor volume and maximum detrusor pressure during bladder contraction) were used to provide objective measures of the treatment effect on bladder function. The impact of treatment on quality of life was assessed using the Incontinence Quality of Life questionnaire. There were significant posttreatment decreases in incontinence episodes from baseline in the 2 BTX-A groups (p </=0.05) but not in the placebo group. In addition, more patients who received BTX-A reported no incontinence episodes during at least 1 posttreatment evaluation period. Positive treatment effects were also reflected by significant improvements in bladder function in the BTX-A groups, as assessed by urodynamics and in patient quality of life. Benefits were observed from the first evaluation at week 2 to the end of the 24-week study. No safety concerns were raised. Intramuscular injections of BTX-A into the detrusor can provide rapid, well tolerated, clinically significant decreases in the signs and symptoms of urinary incontinence caused by neurogenic detrusor overactivity during a 24-week study period.

Efficacy and safety of repeated doses of botulinum toxin type B in type A resistant and responsive cervical dystonia

Efficacy of botulinum toxin type B (BoNT B) for the treatment of type A-resistant (AR) and non-A-resistant (NAR) cervical dystonia (CD) has been demonstrated in several single injection studies. There is little data available on long-term therapy with repeated injection sessions and it is unknown if AR and NAR patients respond in a similar manner over time. To evaluate the long-term efficacy and safety of BoNT B in AR and NAR CD patients, we carried out a prospective, open-label study examining 10 repeated dosing sessions of BoNT B in 34 patients with CD (15 AR and 19 NAR). Dosing was started at 10,000 units and could be increased to 25,000. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and a patient global assessment at each baseline (injection) and Week 4 (peak effect) visit. Change in TWSTRS total was the primary efficacy end point. Data was analyzed using repeated-measures analysis of variance. BoNT B therapy resulted in an overall significant improvement of CD (P<0.001) and improvement was seen in all 10 individual sessions (2.5 years). The magnitude of response decayed over time (P<0.001). There was no difference between AR and NAR patients with regard to dose, treatment effect, or decay in response. The AR group perceived (patient global) treatment as being less effective (P=0.047). Dry mouth frequency decreased with each session despite increasing doses whereas flu-like syndrome and weakness increased. BoNT B therapy provides long-term benefit for CD patients but the magnitude of response diminishes over time. The cause of this decay is probably multifactorial. AR and NAR CD patients respond in a similar fashion.

A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot

Botulinum toxin A (BTX) injections have been used successfully in the treatment of post-stroke foot spasticity, but the optimal dose-response relationship for selected muscles has yet to be established. The aim of this study was to outline beneficial and unwanted effects of three different doses of BTX in the treatment of spastic foot. In this randomised, double-blind, dose-ranging study, 45 spastic feet were randomly allocated to one of three groups, each of which was treated with a different dosage of BTX. The doses were decided on the basis of suggestions in the literature. Outcome measures (Modified Ashworth Scale, Medical Research Council Scale, gait assessment, presence of Achilles tendon clonus, Visual Analogue Scales for Gait Function and Pain, Adverse Effects scale) were applied at baseline, 4 weeks and 4 months after treatment. All the groups showed significant scales scores improvements after treatment with BTX. Group II (mean BTX total dose: 322 U) and Group III (mean BTX total dose: 540 U) showed a greater and more prolonged response than Group I (mean BTX total dose: 167 U). Group III showed the highest rate of adverse effects 4 weeks post-treatment. BTX injections constitute a useful and safe method of improving post-stroke foot spasticity, associated pain, gait speed and function. In particular, the medium BTX dosages (320 UI spread over 2-5 muscles) were found to be both safe and effective in producing long-lasting improvement of spastic foot dysfunction.

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity. Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000 U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS). Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500 U and the peak improvement was at week 8 after injection. A dose of 1000 U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication. Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500 U.

Proper Dose, Preparation, and Storage of Botulinum Neurotoxin Serotype A

The proper dose, preparation, and storage of the formulation of botulinum neurotoxin serotype A (botulinum toxin type A) that is available in the United States (Botox) are described. The recommended dose of botulinum toxin type A varies widely from 1.25 Units to 100 Units, depending on the site. Small initial doses are used for patients without previous treatment with botulinum toxin. Repeat injections often are required, and subsequent doses should be individualized based on response. Larger repeat doses often are used when the response to initial doses is insufficient. An antitoxin is available in the event of accidental poisoning. Botulinum toxin type A is reconstituted with preservative-free 0.9% sodium chloride. Therefore, it should be stored in a refrigerator and discarded if more than four hours elapse after reconstitution. The safe and effective use of botulinum toxin type A requires the proper dose, preparation, and storage by trained personnel only.

A four-month randomized, double-masked evaluation of the efficacy of botulinum toxin type a for the treatment of glabellar lines in women with skin types V and VI

Histologic differences (eg, dermal thickness, collagen fiber) among skin types of different racial/ethnic groups may affect wrinkle formation and response to treatment with botulinum toxin type A. This phase 4 study was designed to evaluate the degree and duration of effect of 20U and 30U of botulinum toxin type A for the treatment of glabellar lines in females with skin types V and VI. Females between the ages of 18 and 65 with a glabellar rhytid score of ≥2 at maximum frown on an investigator-rated, 4-point facial wrinkle scale (0 = none to 3 = severe) were eligible for the study. Patients meeting all inclusion and exclusion criteria were randomized to receive 20U or 30U botulinum toxin type A in the glabellar region. A thorough medical history was conducted at BL. The severity of wrinkles at maximum frown and repose was graded by the investigator and patient on the same 4-point scale at BL and on days 30, 60, 90, and 120. Botulinum toxin type A was administered at the assigned dose, divided among 5 equal injections, into the procerus muscle, each corrugator muscle, and each of 2 sites above the midpupillary line. Adverse events (AEs) and patient satisfaction on a 5-point scale (1 = very satisfied, 5 = very dissatisfied) were also evaluated at each visit. The primary outcome measure was the investigator’s assessment of wrinkle severity at maximum frown and repose. Responder rates were defined as the percentage of subjects with a rating of none (0) or mild (1) on the wrinkle scale. Relapse rates were the percentage of patients who returned to BL wrinkle severity at maximum frown and repose for 2 consecutive visits. Secondary outcome measures were patient assessments of wrinkle severity at maximum frown and repose, patient satisfaction, and AEs. Statistical evaluations were performed on the intent-to-treat population, and included Chi-square tests for homogenicity and linear trend. The incidence, severity, and relationship of AEs to study treatment were analyzed. Preliminary findings indicate that both 20U and 30U doses of botulinum toxin type A are safe in women with skin types V and VI. Results of this study will be reported in detail.

Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy.

To determine the effect of botulinum toxin type A on calcitonin gene-related peptide secretion from cultured trigeminal ganglia neurons. The ability of botulinum toxins to cause muscle paralysis by blocking acetylcholine release at the neuromuscular junction is well known. Previous studies and clinical observations have failed to demonstrate sensory changes related to botulinum toxins or the disease of botulism. Recent studies, however, have suggested that botulinum toxin type A injected into pericranial muscles may have a prophylactic benefit in migraine. This observation has renewed the debate of a mechanism of sensory inhibition mediated by botulinum toxin type A. Primary cultures of rat trigeminal ganglia were utilized to determine whether botulinum toxin type A could directly decrease the release of calcitonin gene-related peptide, a neuropeptide involved in the underlying pathophysiology of migraine. Untreated cultures or cultures stimulated with a depolarizing stimulus (potassium chloride) or capsaicin, an agent known to activate sensory C fibers, were treated for 3, 6, or 24 hours with clinically effective doses of botulinum toxin type A or a control vehicle. The amount of calcitonin gene-related peptide secreted into the culture media following the various treatments was determined using a specific radioimmunoassay. A high percentage (greater than 90%) of the trigeminal ganglia neurons present in 1- to 3-day-old cultures was shown to express calcitonin gene-related peptide. Treatment with depolarizing stimuli (potassium chloride), a mixture of inflammatory agents, or capsaicin caused a marked increase (4- to 5-fold) in calcitonin gene-related peptide released from the trigeminal neurons. Interestingly, overnight treatment of trigeminal ganglia cultures with therapeutic concentrations of botulinum toxin type A (1.6 or 3.1 units) did not affect the amount of calcitonin gene-related peptide released from these neurons. The stimulated release of calcitonin gene-related peptide following chemical depolarization with potassium chloride or activation with capsaicin, however, was greatly repressed by the botulinum toxin, but not by the control vehicle. A similar inhibitory effect of overnight treatment with botulinum toxin type A was observed with 1.6 and 3.1 units. These concentrations of botulinum toxin type A are well within or below the range of tissue concentration easily achieved with a local injection. Incubation of the cultures with toxin for 24, 6, or even 3 hours was very effective at repressing stimulated calcitonin gene-related peptide secretion when compared to control values. These data provide the first evidence that botulinum toxin type A can directly decrease the amount of calcitonin gene-related peptide released from trigeminal neurons. The results suggest that the effectiveness of botulinum toxin type A in the treatment of migraine may be due, in part, to its ability to repress calcitonin gene-related peptide release from activated sensory neurons.

A Prospective, Double-Blind, Randomized, Parallel- Group, Dose-Ranging Study of Botulinum Toxin Type A in Female Subjects With Horizontal Forehead Rhytides

BACKGROUND Botulinum toxin type A is used cosmetically to improve facial lines, but it has not been thoroughly investigated for the treatment of horizontal forehead rhytides. OBJECTIVE To compare the efficacy and safety of three doses of botulinum toxin type A in females with horizontal forehead rhytides and to establish whether the response rate and the duration of response are dose dependent. METHODS Fifty-nine female patients with horizontal forehead rhytides scoring 2 (moderate) or 3 (severe) on the facial wrinkle scale (FWS) were randomly assigned to receive 16, 32, or 48 U of botulinum toxin type A (Botox, Botox Cosmetic; Allergan, Irvine, CA), which was administered to eight injection sites. Half of the dose was administered to the brow depressors and the other half to the elevators. Wrinkle severity was assessed by the investigator and patient using the FWS at baseline, at Weeks 2 and 4, and then every 4 weeks for 48 weeks. RESULTS Improvements in horizontal rhytides were observed in all dosage groups. Significant dose–response trends were observed for rate of improvement at maximum brow elevation (53% in the 48-U group vs. 15% in the 16-U group at 16 weeks) and rate of relapse to baseline (35% in the 48-U group vs. 75% in the 16-U group at 16 weeks) by a trained observer. CONCLUSION Higher botulinum toxin type A doses resulted in greater efficacy and longer duration of effect in the reduction of horizontal rhytides.

A Double-Blind Randomised Placebo-Controlled Evaluation of Three Doses of Botulinum Toxin Type A (Dysport®) in the Treatment of Spastic Equinovarus Deformity after Stroke

Background/Objectives: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport^®) in post-stroke calf spasticity. Methods: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. Results: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002–0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators’ and patients’ assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. Conclusion: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed.