Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial. Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disorders. Efficacy of forced-use therapy in hemiplegic cerebral palsy. Randomized trial of botulinum toxin to prevent pes cavus progression in pediatric Charcot-Marie-Tooth disease type 1A. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Effects of modified constraint induced therapy on upper limb function in subacute stroke patients. Intra-articular botulinum toxin A for refractory shoulder pain: a randomized, double-blinded, placebo-controlled trial. Cyclic functional electrical stimulation does not enhance gains in hand grasp function when used as an adjunct to onabotulinumtoxinA and task practice therapy: a single-blind, randomized controlled pilot study. Response to upper-limb robotics and functional neuromuscular stimulation following stroke.
To investigate the clinical effectiveness of botulinum neurotoxin type A (BoNT) to reduce drooling in children with cerebral palsy (CP).
                A controlled clinical trial was performed in which the results of single-dose BoNT injections in the submandibular glands were compared with treatment with scopolamine. Forty-five children who had CP and experienced severe drooling were enrolled. Drooling severity was measured at baseline, during application of scopolamine, and at different intervals after BoNT injections up to 24 weeks, using the Drooling Quotient (DQ), the Teacher Drooling Scale (TDS), and Visual Analog Scales (VAS).
                Drooling was reduced during scopolamine application as well as after BoNT injections. Compared with baseline, the mean DQ showed a significant decrease throughout the study. Greatest reductions were achieved 2 to 8 weeks after BoNT injection. No significant differences were found between scopolamine measurements and those up to 24 months after BoNT injection. Using VAS, parents recorded the effect on drooling in which significant differences were found between baseline VAS score and all follow-up assessments. According to our definition of "success to therapy," demanding a 2-point decrease on the TDS, 61.5% of patients responded to BoNT injections. Analysis of the DQ demonstrated a response rate of 53% of the patients to scopolamine and 48.7% to BoNT until 24 weeks after BoNT injections, the actual duration of this study. As a reaction to scopolamine, 71.1% of the patients had moderate to severe side effects. Only nonsevere, incidental side effects were reported after BoNT injections.
                During scopolamine application as well as after intraglandular BoNT injections, a clinically relevant reduction in drooling was achieved in children with CP, demonstrating maximum effect 2 to 8 weeks after injections. This is the first controlled clinical trial that confirmed a significant effect of BoNT injections in the treatment of drooling. General anesthesia was needed for all children. BoNT injections show fewer and less serious side effects than transdermal scopolamine treatment. 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 determine the efficacy of forced-use therapy (FUT) on the improvement of upper-extremity function in children with hemiplegic cerebral palsy (CP).
                Prospective case series.
                Outpatient ambulatory clinic in South Korea.
                Thirty-one patients with hemiplegic CP were assigned to the FUT group (n=18) or to the control group (n=13). The mean age of the patients in the FUT group was 33.2 months and in the control group it was 43.2 months.
                The FUT group wore a short-arm Scotchcast on the unaffected arm for 6 weeks and also participated in a conventional rehabilitation program that included stretching exercises and functional occupational therapy for the upper extremity. The control group underwent the conventional rehabilitation program only.
                Hand function tests, including the box and block test (BBT), Erhardt Developmental Prehension Assessment (EDPA), and WeeFIM instrument taken before and after 6 weeks of treatment.
                Before treatment, there was no significant difference between groups in the BBT, EDPA, and WeeFIM scores. After 6 weeks of treatment, however, the FUT group showed significant improvement in the affected arm in the BBT and EDPA scores, compared with the control group (P<.05). The self-care score on the WeeFIM was also significantly improved in the FUT group (P<.05).
                FUT combined with a conventional rehabilitation program appears to be more effective than a rehabilitation program alone in improving affected hand function in children with hemiplegic CP. Pes cavus in Charcot-Marie-Tooth disease type 1A (CMT1A) is thought to be due to muscle imbalance of the lower leg. Botulinum toxin type A (BoNT-A) can modify foot deformity in other conditions of muscle imbalance. We tested the safety and effectiveness of BoNT-A on pes cavus progression in pediatric CMT1A. A 24-month, randomized, single-blind trial of BoNT-A was undertaken in 10 affected children (20 legs), aged 3-14 years. The treated leg received intramuscular BoNT-A injections at 6-month intervals in the tibialis posterior and peroneus longus. The control leg received no injections. Primary outcome was radiographic alignment at 24 months. Secondary outcomes were foot posture, ankle flexibility, and strength, assessed every 6 months. Radiographically, BoNT-A produced a small non-significant reduction in cavus progression. There was no effect of BoNT-A on secondary outcomes. There were no serious adverse events. At 24 months, the intramuscular BoNT-A injections proved safe and well-tolerated but did not affect the progression of pes cavus in CMT1A. 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. To examine the feasibility and efficacy of a modified constraint induced therapy protocol on stroke patients.
                This study was carried out during the period from August 2001 to January 2002 at the Riyadh Medical Complex, Riyadh, Kingdom of Saudi Arabia. Six stroke patients with subacute cerebrovascular accident (<6 months) were included in the study. Three male and 3 female patients with a mean age of 54.3+/-6.9 years (range 45-67 years), and mean duration of hemiparesis of 4.7 months (range 2.3-5.8 months). They were divided randomly into 3 groups of 2 patients. The first 2 patients (constraint induced therapy group) participated in half an hour of physical and occupational therapy sessions 3 times per week for 10 weeks. During the same period, their unaffected arms and hands were restrained 5 days per week for 5 hours identified as times of frequent use. The second 2 patients (traditional therapy group) received regular therapy administered after 10 weeks. The last 2 patients (control group) received no therapy. The Fugl-Meyer Assessment of Motor Recovery After Stroke (Fugl), Action Research Arm Test (ARA), Wolf Motor Function Test (WMFT), and Motor Activity Log (MAL) were administered to the patients.
                Patients receiving modified constraint induced therapy exhibited substantial improvement on the Fugl, ARA, and WMFT, as well as increases in amount and quality of use of the limb using the MAL. While patients receiving traditional physical and occupational therapy, and no therapy patients exhibited few improvements.
                Modified constraint induced therapy may be an efficacious method of improving function and use of the affected arms in stroke patients exhibiting learned nonuse. We compared the short-term efficacy and safety of intra-articular (IA) botulinum toxin A (BoNT/A) to IA-placebo in patients with chronic, refractory shoulder joint pain. Forty-three shoulder joints in patients with moderate-to-severe shoulder arthritis pain were randomized to receive (1) 100 units IA-BoNT/A + lidocaine or (2) IA-saline + lidocaine. The following outcomes were compared using analysis of covariance: (1) primary: change in pain severity on a visual analog scale at 1 month (VAS, 0 cm to 10 cm); (2) secondary: Shoulder Pain and Disability Index (SPADI) disability subscale, quality of life on short-form (SF)-36 subscales, percent of patients who achieved at least a 30% decrease or a 2-point reduction in VAS pain (clinically meaningful pain relief), and safety. Both BoNT/A (n = 21) and placebo (n = 22) groups were comparable at baseline. At 1 month post-injection, the VAS pain reduction was significantly more in the BoNT/A group versus the placebo group (-2.4 vs -0.8; P-value = 0.014). When comparing BoNT/A with the placebo group at 1 month, it was observed that 5 SF-36 subscale scores improved significantly (P </= 0.035), and the SPADI disability improved more with a trend toward significance (51.5 +/- 4.4 vs 64.9 +/- 3.9; P = 0.083). In addition, clinically meaningful pain relief occurred in 61% versus 36% patients (P = 0.22). The total number of adverse events was similar, which included 50 events in the BoNT/A group versus 46 events in the placebo group. A single injection of BoNT/A produced statistically significant and clinically meaningful pain relief and improvement in quality of life in patients with chronic refractory moderate/severe shoulder arthritis pain at 1 month. These data provide evidence to support the efficacy of this novel neurotoxin therapy that needs to be confirmed in a multicenter, randomized trial. To determine whether onabotulinumtoxinA injections and task practice training with or without functional electrical stimulation (FES) improve upper limb motor function in chronic spastic hemiparesis.
                Randomized controlled trial.
                Outpatient spasticity clinic.
                Participants (N=23) had chronic spastic hemiparesis with moderate-severe hand impairment based on Chedoke-McMaster Assessment greater than or equal to 2.
                OnabotulinumtoxinA injections followed by 12 weeks of postinjection task practice. Participants randomly assigned to FES group were also fitted with an orthosis that provided FES.
                Motor Activity Log (MAL)-Observation was the primary outcome. Secondary outcomes were Action Research Arm Test (ARAT) and MAL-Self-Report.
                For the entire cohort, MAL-Observation mean item scores improved significantly from baseline to week 6 (P=.005) but did not remain significant at week 12. MAL-Self-Report mean item scores improved significantly (P=.009) from baseline to week 6 and remained significantly higher (P=.014) at week 12. ARAT total scores also improved significantly from baseline to week 6 (P=.018) and were sustained at week 12 (P=.032). However, there were no significant differences between the FES and no-FES groups for any outcome variable over time.
                Rehabilitation strategies that combine onabotulinumtoxinA injections and task practice therapy are feasible and effective in improving upper-limb motor function and reducing spasticity in patients with chronic spastic hemiparesis. However, the cyclic FES protocol used in this study did not increase gains achieved with the combination of onabotulinumtoxinA and task practice alone. Twelve moderately to severely involved chronic stroke survivors (>12 mo) were randomized to one of two treatments: robotics and motor learning (ROB-ML) or functional neuromuscular stimulation and motor learning (FNS-ML). Treatment was 5 h/d, 5 d/wk for 12 wk. ROB-ML group had 1.5 h per session devoted to robotics shoulder and elbow (S/E) training. FNS-ML had 1.5 h per session devoted to functional neuromuscular stimulation (surface electrodes) for wrist and hand (W/H) flexors/extensors. The primary outcome measure was the functional measure Arm Motor Ability Test (AMAT). Secondary measures were AMAT-S/E and AMAT-W/H, Fugl-Meyer (FM) upper-limb coordination, and the motor control measures of target accuracy (TA) and smoothness of movement (SM). ROB-ML produced significant gains in AMAT, AMAT-S/E, FM upper-limb coordination, TA, and SM. FNS-ML produced significant gains in AMAT-W/H and FM upper-limb coordination.
This systematic review found high level evidence supporting the use of BoNT-A as an adjunct to managing the upper limb in children with spastic CP. BoNT-A should not be used in isolation but should be accompanied by planned occupational therapy.
Further research is essential to identify children most likely to respond to BoNT-A injections, monitor longitudinal outcomes, determine timing and effect of repeated injections and the most effective dosage, dilution and volume schedules. The most effective adjunct therapies including frequency and intensity of delivery also requires investigation.