Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disorders. Treatment of sialorrhea in children with cerebral palsy: a double-blind placebo controlled trial. Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients. Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia. Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study. Results of a prospective randomized trial of botulinum toxin therapy in acute unilateral sixth nerve palsy. Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates. Esophageal achalasia: intrasphincteric injection of botulinum toxin A versus balloon dilation. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.
The primary aim of this randomized, controlled trial was to assess the effectiveness of botulinum toxin A (BoNT-A) injections into the submandibular and parotid glands on drooling in children with cerebral palsy (CP) and other neurological disorders. Secondary aims were to ascertain the duration of any such effect and the timing of maximal response. Of the 48 participants (27 males, 21 females; mean age 11y 4mo [SD 3y 3mo], range 6-18y), 31 had a diagnosis of CP and 15 had a primary intellectual disability; 27 children were non-ambulant. Twenty-four children randomized to the treatment group received 25 units of BoNT-A into each parotid and submandibular gland. Those randomized to the control group received no treatment. The degree and impact of drooling was assessed by carers using the Drooling Impact Scale questionnaire at baseline and at monthly intervals up to 6 months postinjection/baseline, and again at 1 year. Maximal response was at 1 month at which time there was a highly significant difference in the mean scores between the groups. This difference remained statistically significant at 6 months. Four children failed to respond to the injections, four had mediocre results, and 16 had good results. While the use of BoNT-A can help to manage drooling in many children with neurological disorders, further research is needed to fully understand the range of responses. To prospectively study the efficacy and safety of intraparotid gland injection of Botulinum neurotoxin serotype A (Dysport) for the treatment of sialorrhea (drooling) in children with cerebral palsy (CP).
                Twenty-four children, ages 21 months to 7 years, were recruited and randomized to receive either treatment with 100U Botulinum toxin or placebo. Rating scales for the frequency and severity of drooling were performed at the time of injection, at 1 month, and at baseline prior to the second injection. A second set of injections of either 140U of drug or placebo was given 4 months later, and the same rating scales were used. Eight patients declined the second injection. Due to high dropouts in the placebo group in second set of injections, statistical analysis was performed for the results of the initial injection only.
                Scores of the median frequency (p=0.034) and severity (p=0.026) of drooling were reduced in the treatment group. Median total score also declined in the treatment group (p=0.027). After the second injection, five out of nine patients injected with the drug showed a decline in the total score; including three patients who did not respond to the first injection. Only two patients experienced transient increase in drooling after the treatment with the drug.
                Botulinum toxin is an effective and safe treatment option for drooling in children with CP. Twenty ALS patients with sialorrhea refractory to medical therapy were enrolled in this double-blind, randomized study to receive either 2,500 U of botulinum toxin type B (BTxb) or placebo into the bilateral parotid and submandibular glands using electromyographic guidance. Patients who received BTxb reported a global impression of improvement of 82% at 2 weeks compared to 38% of those who received placebo (P < 0.05). This significant effect was sustained at 4 weeks. At 12 weeks, 50% of patients who received BTxb continued to report improvement compared to 14% of those who received placebo. There were no significant adverse events, including dysphagia, in the BTxb group, and there was no significant increase in the rate of decline of vital capacity. Intrasphincteric injection of botulinum toxin has been suggested as an alternative treatment modality in esophageal achalasia. A controlled trial comparing botulinum toxin, placebo, and pneumatic dilation is reported.
                Sixteen patients received random intrasphincteric injections of either botulinum toxin or saline. The efficacy of treatment was assessed by symptom score, esophageal manometry, and scintigraphy. In case of failure, pneumatic dilation was performed.
                One month after injection, symptoms had improved in all patients treated with botulinum toxin (symptom score, 0.9 +/- 0.6 vs. 5.5 +/- 1.4; P < 0.02). In the placebo group, symptoms were unchanged in all patients, who were all dilated. Lower esophageal sphincter pressure decreased by 49% after treatment with botulinum toxin (P < 0.03) and by 72% after dilation (P < 0.01). Similarly, esophageal retention decreased by 47% after treatment with botulinum toxin (P < 0.02) and by 59% after dilation (P < 0.02). No significant difference in symptom score and esophageal function test results was found between patients treated with botulinum toxin injections and those undergoing dilation. However, 7 of the 8 patients in the botulinum toxin group required a second injection because of recurrent dysphagia.
                Treatment of achalasia with botulinum toxin was as effective as pneumatic dilation in relieving symptoms and improving esophageal function. The effect of the first injection was temporary, but the effect of the second injection lasted longer. We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy.
                A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl. Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment.
                In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup. There were no local side effects with either treatment. Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup.
                In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin. Forty-seven patients entered a prospective randomized trial to assess the effect of early botulinum neurotoxin A treatment to the ipsilateral antagonist medial rectus on the ultimate recovery rate of acute unilateral sixth nerve palsy. Twenty-two patients received injections and 25 acted as controls. The overall etiologies were microvascular (72.3%), unknown (17%), multiple sclerosis (6%), and one case each of central nervous system (CNS) sarcoidosis and basilar artery ectasia. Eighty-three percent of the patients entered the trial within 2 weeks of the onset of symptoms and 95.7% within 3 weeks. The controls had a final recovery rate of 20/25 (80%), and the injected group had a final recovery rate of 19/22 (86%). No serious side effects were encountered. We conclude that there is no evidence for a prophylactic effect of botulinum toxin in the group that we have studied. This study was designed to assess whether addition of glyceryl trinitrate to botulinum toxin improves the healing rate of glyceryl trinitrate-resistant fissures over that achieved with botulinum toxin alone.
                Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group A) and botulinum toxin plus placebo paste (Group B). Patients were seen at baseline, four and eight weeks, and six months. The primary end point was fissure healing at eight weeks. Secondary end points were symptomatic relief, need for surgery, side effects, and reduction in maximum resting and squeeze pressures.
                Thirty patients were randomized. Two-thirds of patients had maximum anal resting pressures below or within the normal range at entry to the study. Healing rates in both treatment groups were disappointing. There was a nonsignificant trend to better outcomes in Group A compared with Group B in terms of fissure healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and resort to surgery (27 vs. 47 percent).
                There is some evidence to suggest that combining glyceryl trinitrate with botulinum toxin is superior to the use of botulinum toxin alone for glyceryl trinitrate-resistant anal fissure. The poor healing rate may reflect the fact that many of the patients did not have significant anal spasm at trial entry. In patients with esophageal achalasia, pneumatic dilation is the treatment of choice, but it bears the risk of perforation in about 4% of cases. A new nonsurgical method, intrasphincteric injection of botulinum toxin A, has shown promising initial results, and we thus undertook this study to compare the long-term outcome of these two methods.
                In a prospective randomized study, 24 patients with definitive esophageal achalasia were divided into two equal groups and underwent either balloon dilation or injection of botulinum toxin (20 U injected into each of the four quadrants in the lower esophageal sphincter). The outcome was assessed on the basis of a symptom score documented before treatment and at regular intervals for two and a half years thereafter. Complications associated with the two techniques were also documented.
                No relevant complication occurred in either of the treatment groups. Initially, dilation was successful in 10 of 12 patients (83%), and botulinum toxin injection in 9 of 12 patients (75%). The symptom scores showed no significant differences between the two groups before and one month after treatment. Over the two and a half year follow-up, however, all nine successfully treated patients in the botulinum toxin group experienced recurrence of symptoms, but only four of the ten patients (40%) in the dilation group.
                The two treatment methods initially had equal success rates, but in the long term the effect of the botulinum toxin injection was statistically significantly shorter than that of balloon dilation. As fewer risks are associated with the injection treatment, studies should be undertaken either to identify patient subgroups in whom botulinum toxin can be effective long-term or to test substances with longer-lasting effects. To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD).
                Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients.
                The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16.
                A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group.
                Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.
There is some evidence for use of botulinum toxin injections to salivary glands for the treatment of sialorrhea in MND. Further research is required on this important symptom. Data are needed on the problem of sialorrhea in MND and its measurement, both by patient self report measures and objective tests. These will allow the development of better randomized controlled trials.