Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections

Introduction: Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Methods: Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8). Results: The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber‐type grouping. Conclusions: These experiments demonstrate a disproportionately greater effect of repeated BoNT injections. Muscle Nerve 52: 649–657, 2015     

Location and severity of spasticity in the first 1–2 weeks and at 3 and 18 months after stroke

Background and purpose: There is no consensus concerning the location or severity of spasticity, or how this changes with time after stroke. The purpose was to describe: the location and severity of spasticity, in different muscle groups, during the first 1–2 weeks and at 3 and 18 months after stroke; the association between the severity of spasticity and control of voluntary movements; and the occurrence of spasticity in younger versus older patients. Methods: In a cohort of consecutive patients, the following parameters were assessed during the first 1–2 weeks (n = 109) and at 3 (n = 95) and 18 (n = 66) months after first‐ever stroke: spasticity, by the Modified Ashworth Scale in different muscle groups; plantar‐flexor clonus, by physical examination; and movement function, by the Lindmark Motor Assessment Scale. Results: During the first 1–2 weeks and at 3 months after stroke, spasticity was most common in the anti‐gravity muscles. The severity of upper extremity spasticity increased over time (P < 0.05). Upper extremity spasticity and movement scores were moderately associated (r = ?0.61, P < 0.05). At 3 months, spasticity was more common amongst the younger patients (P < 0.05). Conclusions: The results confirm that spasticity is most common in the anti‐gravity muscles and is associated with the control of voluntary movements. As the severity of spasticity also increased after 3 months, when neurally mediated spasticity is expected to have passed its peak, intrinsic muscle changes may play a larger role than neural components with the passage of time after stroke.     

Determinants of responsiveness to botulinum toxin,casting, and bracing in the treatment of spastic equinus in children with cerebral palsy

Aim The objective was to determine whether specific intrinsic (age, pattern of cerebral palsy [CP], child’s motivation) and extrinsic (number of treatments, parenting stress) characteristics were associated with responsiveness to botulinum toxin A (BoNT‐A) injections in children with CP 3 months after injection into the gastrocnemius muscle. Method Children with hemiplegia or diplegia recruited from a BoNT‐A programme were evaluated before and 3 months following injection of BoNT‐A into the gastrocnemius. Outcome measures included muscle tone, range of motion, gait pattern, level of ambulation, gross motor function, and functional independence. Determinants of responsiveness to BoNT‐A considered were age, number of treatments, distribution of CP, parenting stress, and motivation. Results Thirty‐one children were recruited (17 males, 14 females) – 22 with hemiplegia and nine with diplegia. Twenty‐eight were classified at Gross Motor Function Classification System (GMFCS) level I and three at level III. The mean age was 6 years 4 months (SD 2y 11mo). Younger age (p=0.015) and fewer number (p=0.024) of BoNT‐A treatments were associated with greater change in gross motor function. Child’s motivation and parenting stress were significantly associated with improvements in muscle tone (p=0.006–0.017), passive range of motion (p=0.008–0.033), gait pattern (p=0.005–0.042), level of ambulation (p=0.001–0.043), and functional independence (p=0.004–0.027). Interpretation The results indicate that child, family, and treatment characteristics influence the degree of responsiveness to BoNT‐A treatment. The contribution of contextual factors (personal and environmental) on responsiveness may be underappreciated in children with CP.     

The impact of botulinum toxin A and abduction bracing on long-term hip development in children with cerebral palsy

Aim To study the long‐term impact of 3 years of botulinum toxin A (BoNT‐A) injections and abduction bracing on hip development in children with bilateral spastic cerebral palsy (CP). We wanted to know if early treatment improved hip development and reduced the need for surgery. Method A long‐term review of hip morphology and surgery requirements in children who participated in a multicentre, randomized controlled trial. The trial investigated short‐term effects of BoNT‐A injections combined with an abduction brace, compared with usual care, on hip displacement in children with bilateral spastic CP. Results Forty‐six children with bilateral spastic CP (31 males, 15 females; 10 with diplegia, 36 with quadriplegia; mean age at enrolment of 3y 2mo, mean age at most recent clinical review 13y 11mo [range 10y 6mo–16y 8mo]; three children in Gross Motor Function Classification System level II, 11 in level III, 20 in level IV, 12 in level V) were followed for a mean of 10 years 10 months from recruitment to the trial. Mean migration percentage was 15.9% in the BoNT‐A group and 15.2% in the comparison group (t=0.26, p=0.79). Eighty‐nine percent of hips in the treatment group and 91% hips in the comparison group had satisfactory development, using a valid scale (Mann–Whitney U test=867.50, z=?1.59, p=0.11). Forty children had preventive surgery (21 treatment group, 19 comparison group) and 18 children had reconstructive surgery (10 treatment, 8 comparison). Interpretation In children with bilateral spastic CP, early treatment with BoNT‐A and hip abduction bracing does not reduce the need for surgery or improve hip development at skeletal maturity.     

Botulinum toxin A versus B in sialorrhea: A prospective,randomized, double‐blind,crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease

Background: Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions. Methods: Consecutive patients affected by Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD) accompanied by severe drooling were randomized to receive botulinum neurotoxin type A (BoNT‐A) or B (BoNT‐B) injections into the salivary glands. Following the first treatment, when sialorrhea returned to baseline (at least three months after the first injection), subjects were re‐treated with the other serotype. Ultrasound‐guided injections into parotid and submandibular glands were bilaterally performed: total doses were 250 U BoNT‐A (Dysport) and 2500 U BoNT‐B (Neurobloc). Objective (cotton roll weight) and subjective (ad hoc clinical scales) evaluations were performed at baseline, after 1 and 4 weeks, and every 4 weeks until drooling returned to baseline. Results: Twenty‐seven patients (15 ALS and 12 PD) were enrolled, fourteen completed the study. BoNT‐A and BoNT‐B treatments gave both subjective and objective improvements in all patients. The latency was significantly shorter after BoNT‐B treatments (3.2 ± 3.7 days) compared to BoNT‐A (6.6 ± 4.1 days; P = 0.002). The mean benefit duration was similar at 75 and 90 days for BoNT‐A and BoNT‐B, respectively (P = NS). The only toxin‐related side effect was a change to saliva thickness. Conclusions: Either 250 U Dysport or 2500 U Neurobloc have similar effectiveness and safety in controlling sialorrhea. BoNT‐B has a shorter latency and comparable duration. Cost analysis, considering the doses used in this study protocol favored BoNT‐B treatment. © 2011 Movement Disorder Society     

A randomized,double‐blind,placebo‐controlled trial of pridopidine in Huntington's disease

We examined the effects of 3 dosages of pridopidine, a dopamine‐stabilizing compound, on motor function and other features of Huntington's disease, with additional evaluation of its safety and tolerability. This was a randomized, double‐blind, placebo‐controlled trial in outpatient neurology clinics at 27 sites in the United States and Canada. Two hundred twenty‐seven subjects enrolled from October 24, 2009, to May 10, 2010. The intervention was pridopidine, either 20 (n=56), 45 (n=55), or 90 (n=58) mg daily for 12 weeks or matching placebo (n=58). The primary outcome measure was the change from baseline to week 12 in the Modified Motor Score, a subset of the Unified Huntington's Disease Rating Scale Total Motor Score. Measures of safety and tolerability included adverse events and trial completion on the assigned dosage. After 12 weeks, the treatment effect (relative to placebo, where negative values indicate improvement) of pridopidine 90 mg/day on the Modified Motor Score was ?1.2 points (95% confidence interval [CI], ?2.5 to 0.1 points; P = .08). The effect on the Total Motor Score was ?2.8 points (95% CI, ?5.4 to ?0.1 points; nominal P = .04). No significant effects were seen in secondary outcome measures with any of the active dosages. Pridopidine was generally well tolerated. Although the primary analysis did not demonstrate a statistically significant treatment effect, the overall results suggest that pridopidine may improve motor function in Huntington's disease. The 90 mg/day dosage appears worthy of further study. Pridopidine was well tolerated. © 2013 International Parkinson and Movement Disorder Society     

Effectiveness of functional progressive resistance exercise strength training on muscle strength and mobility in children with cerebral palsy: a randomized controlled trial

Aim To evaluate the effectiveness of functional progressive resistance exercise (PRE) strength training on muscle strength and mobility in children with cerebral palsy (CP). Method Fifty‐one children with spastic uni‐ and bilateral CP; (29 males, 22 females; mean age 10y 5mo, SD 1y 10mo, range 6y 0mo–13y 10mo; Gross Motor Function Classification System levels I–III) were randomized to the intervention group (n=26) or the control group (n=25, receiving usual care). The intervention group trained for 12 weeks, three times a week, on a five‐exercise circuit, which included a leg‐press and functional exercises. The training load progressively increased based on the child’s maximum level of strength, determined by the eight‐repetition maximum. Muscle strength (measured with hand‐held dynamometry and a six‐repetition maximum leg‐press test), mobility (measured with the Gross Motor Function Measure, two functional tests, and a mobility questionnaire), and spasticity (measured by the appearance of a catch) were evaluated before, during, directly after, and 6 weeks after the end of training by two blinded research assistants. Results Directly after training, there was a statistically significant effect (p<0.05) on muscle strength (knee extensors +12% [0.56N/kg; 95% confidence interval {CI} 0.13–0.99]; hip abductors +11% [0.27N/kg; 95% CI 0.00–0.54]; total +8% [1.30N/kg; 95% CI 0.56–2.54]; six‐repetition maximum +14% [14%; 95% CI 1.99–26.35]), but not on mobility or spasticity. A detraining effect was seen after 6 weeks. Interpretation Twelve weeks of functional PRE strength training increases muscle strength up to 14%. This strength gain did not lead to improved mobility.     

Effectiveness of sedation using nitrous oxide compared with enteral midazolam for botulinum toxin A injections in children

This randomized, double‐blind, placebo‐controlled study compared the efficacy of inhaled nitrous oxide (N₂O) with enteral midazolam for sedation of children with cerebral palsy (CP) undergoing botulinum toxin A (BoNT‐A) injections. Fifty children (29 males, 21 females; mean age 8y 2mo [SD 4y 5mo]; range 1–16y) were randomized to sedation with N₂O (n=25) or midazolam (n=25). Groups were similar in type of CP (diplegia, 11; triplegia, three; quadriplegia, 16; hemiplegia, 16; other, three) and Gross Motor Function Classification System level (Level I, 4; II, 24; III, 4; IV, 13; V, 5). Both groups were equally sedated at time of injection (p=0.661), but those in the midazolam group were more sedated at time of discharge (p<0.001). N₂O was more effective in reducing pain compared with midazolam as measured using the Face, Legs, Activity, Cry, Consolability (FLACC) scale (p=0.010), parental estimate of pain (p=0.009), and nursing estimate of pain (p=0.007). Parents in the N₂O group rated it better than prior sedation with midazolam for BoNT‐A injections (p=0.031). Physicians and nurses reported no difference in ease of procedure between the groups. One child in the midazolam group and eight in the N₂O group had adverse effects, all of which resolved promptly. N₂O appears to be an effective means of sedation for children undergoing outpatient BoNT‐A injections.     

Botulinum neurotoxin type A injections reduce spasticity in mild to moderate hereditary spastic paraplegia— Report of 19 cases

Hereditary spastic paraplegia (HSP) is characterized by lower extremity spasticity. Symptomatic therapy generally includes physical therapy and oral antispastic agents, in selected cases intrathecal baclofen. Because of the positive results in other treatments of spasticity, the use of botulinum neurotoxin type A (BoNT‐A) might also be considered for patients with HSP. We report the effect of BoNT‐A injections in 19 unselected patients with HSP treated by the members of the German Spasticity Education Group. In 17 patients, the modified Ashworth scale had improved by one point. In one patient, it improved by three points. Most of the patients reported reduction of spasticity. BoNT‐A injections were continued in 11 of 19 patients (57.9%). All of the patients with continued injections had a good or very good global subjective improvement. Patients with less pronounced spasticity and patients with accompanying physical therapy tended to exhibit a better effect. Only four patients reported adverse effects which were increased weakness in three patients and pain in one patient. BoNT‐A injections appear to reduce spasticity effectively and safely, especially in patients with mild to moderate spasticity. The preliminary results of our case series should encourage larger studies of BoNT‐A injections in HSP. © 2007 Movement Disorder Society     

Modified constraint-induced therapy for children with hemiplegic cerebral palsy: a randomized trial

Aim Conventional constraint‐based therapies are intensive and demanding to implement, particularly for children. Modified forms of constraint‐based therapies that are family‐centred may be more acceptable and feasible for families of children with cerebral palsy (CP)‐but require rigorous evaluation using randomized trials. The aim of this study was to determine the effects of modified constraint‐induced therapy compared with intensive occupational therapy on activities of daily living and upper limb outcomes in children with hemiplegic CP. Method In this assessor‐blinded pragmatic randomized trial, 50 children (27 males, 23 females; age range 19mo–7y 10mo) with hemiplegic CP were randomized using a concealed allocation procedure to one of two 8‐week interventions: intensive occupational therapy (n=25), or modified constraint‐induced therapy (n=25). Manual Ability Classification System (MACS) levels of the participants were, level I n=2, II n=37, III n=8, and level IV n=1; Gross Motor Function Classification System (GMFCS) levels were, level I n=33, level II n=15, and level III n=1. Participants were recruited through three specialist CP centres in Australia and randomized between January 2008 and April 2010. Children randomized to modified constraint‐induced therapy wore a mitt on the unaffected hand for 2 hours each day, during which time the children participated in targeted therapy. The primary outcome was the Canadian Occupational Performance Measure (COPM – measured on a 10‐point scale) at completion of therapy. Other outcome measures were Goal Attainment Scaling, Assisting Hand Assessment, Pediatric Motor Activity Log, Modified Ashworth Scale, Modified Tardieu Scale, and a parent questionnaire. Assessments were carried out at 10 weeks and 6 months following randomization. Results All participants were included in the analysis. Between‐group differences for all outcomes were neither clinically important nor statistically significant. The mean difference in COPM was 0.3 (95% confidence interval [CI] −0.8 to 1.4; p=0.61) and mean difference in COPM satisfaction was 0.1 (95% CI −1.1 to 1.2; p=0.90). Minor adverse events were reported by five of the 25 participants in the modified constraint‐induced therapy group and by one of the 25 in the intensive occupational therapy group. All adverse events were related to participants’ lack of acceptance of therapy. Interpretation Modified constraint‐induced therapy is no more effective than intensive occupational therapy for improving completion of activities of daily living or upper limb function in children with hemiplegic CP.     

Split‐screen video demonstration of sonography‐guided muscle identification and injection of botulinum toxin

A standardization of injection procedures for the various botulinum toxin (BoNT) indications has not been achieved to date. One established option to guide the therapist's needle is sonography guidance. It provides real‐time visualization of the injection process, which is quick, allows perfect precision, and the procedure as such is painless. To demonstrate these qualities, we have recorded six split‐screen video segments that show the handling of the probe and the needle during BoNT injections concurrently with the respective cross‐sectional sonography recordings. The video sequences show differentiation of the pollicis longus muscle and individual finger flexor fascicles, needle tracking, and real‐time sonography‐guided injection of the gastrocnemius, rectus femoris, and iliopsoas muscles. We hope this short presentation will help to encourage a more widespread use of the technique as well as further research on sonography guidance for precise delivery of BoNT injections to various target muscles. © 2010 Movement Disorder Society     

Dose response with onabotulinumtoxinA for post‐stroke spasticity: A pooled data analysis

Clinical trials demonstrate that onabotulinumtoxinA reduces upper limb post‐stroke spasticity, with therapeutic response influenced by injected dose. Individual studies provide limited insight regarding muscle group‐specific dose–response relationships. Our objective was to characterize dose–response relationships between onabotulinumtoxinA and muscle tone in specific upper limb muscles. Individual patient data from seven multicenter, randomized, double‐blind, placebo‐controlled trials were pooled. Of 544 post‐stroke patients enrolled, 362 received onabotulinumtoxinA and 182 received placebo, injected into the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and/or biceps brachii (BB). Ashworth Scale score change at week 6 (AshworthCBL) was the primary outcome measure for muscle tone. For a broader analysis of response, AshworthCBL/onabotulinumtoxinA dosage relationships were characterized using three techniques: (1) AshworthCBL plotted as a function of onabotulinumtoxinA dose in Units (U) [dose–response curve]; (2) mean AshworthCBL per onabotulinumtoxinA dose depicting the responses seen with specific dose injection clusters/groups for each specific muscle group; and (3) onabotulinumtoxinA dose estimated to produce a mean 1‐point decrease in AshworthCBL as an indicator of clinically meaningful benefit of treatment. Increasing onabotulinumtoxinA doses produced greater AshworthCBLs (muscle tone improvements). The maximal week 6 response (E_max) model indicated a saturating dose–response relationship, with mean E_max AshworthCBL values of ‐1.48, ‐1.48, ‐0.63, ‐0.77, and ‐0.61 in the FCR, FCU, FDS, FDP, and BB, respectively. OnabotulinumtoxinA doses estimated to produce a mean 1‐point decrease in AshworthCBL were: 22.5U, 18.4U, 66.3U, 42.5U in the FCR, FCU, FDS, and FDP, respectively, and not determinable in the BB. These analyses demonstrate a saturating effect of greater muscle tone improvements with increasing onabotulinumtoxinA doses in post‐stroke spasticity patients. These findings suggest potentially effective onabotulinumtoxinA doses in selected muscle groups in this study population. © 2010 Movement Disorder Society.     

No change in calf muscle passive stiffness after botulinum toxin injection in children with cerebral palsy

Aim Stiffness and shortening of the calf muscle due to neural or mechanical factors can profoundly affect motor function. The aim of this study was to investigate non‐neurally mediated calf‐muscle tightness in children with cerebral palsy (CP) before and after botulinum toxin type A (BoNT‐A) injection. Method Sixteen children with spastic CP (seven females, nine males; eight at Gross Motor Function Classification System level I, eight at level II; age range 4–10y) and calf muscle spasticity were tested before and during the pharmaceutically active phase after injection of BoNT‐A. Measures of passive muscle compliance and viscoelastic responses, hysteresis, and the gradient of the torque–angle curve were computed and compared before and after injection. Results Although there was a slight, but significant increase in ankle range of motion after BoNT‐A injection and a small, significant decrease in the torque required to achieve plantigrade and 5° of dorsiflexion, no significant difference in myotendinous stiffness or hysteresis were detected after BoNT‐A injection. Interpretation Despite any effect on neurally mediated responses, the compliance of the calf muscle was not changed and the muscle continued to offer significant resistance to passive motion of the ankle. These findings suggest that additional treatment approaches are required to supplement the effects of BoNT‐A injections when managing children with calf muscle spasticity.     

Thickened saliva after effective management of drooling with botulinum toxin A

Aim The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT‐A) injections. Method We enrolled 15 children (11 males and six females; age range 3–17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function Classification System level IV or V; and two children with intellectual disability (IQ <70) who experienced moderate to severe drooling. Salivary flow rate and drooling quotient were measured at baseline and at different times after BoNT‐A injections up to 24 weeks. The mucin concentration of saliva was analysed before and after BoNT‐A treatment. Results Both submandibular salivary flow rate (baseline 0.38mL/min; 24wks after injection 0.26mL/min) and drooling quotient (baseline 42.5%; 24wks 28.80%) were substantially reduced, with a concomitant increase in mucin concentration within 8 weeks after BoNT‐A injection (from 0.612 to 1.830U/mL). The parents of nine children observed thickened saliva. Swallowing and chewing were problematic in seven children. Two of these children needed treatment with mucolytics because of pooling of thickened saliva in the throat. Interpretation When making decisions about the use of BoNT‐A, the risk of problems with masticatory and swallowing functions as a result of thickening of saliva after BoNT‐A treatment should be taken into account.     

Salivary gland botulinum toxin injections for drooling in children with cerebral palsy and neurodevelopmental disability: a systematic review

Aim The aim of this paper was to systematically review the efficacy and safety of botulinum toxin (BoNT) injections to the salivary glands to treat drooling in children with cerebral palsy and neurodevelopmental disability. Method A systematic search of The Cochrane Central Register of Controlled Trials, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and the Physiotherapy Evidence Database (PEDro) was conducted (up to 1 October 2011). Data sources included published randomized controlled trials (RCTs) and prospective studies. Results Sixteen studies met inclusion criteria. Three outcome measures support the effectiveness of BoNT for drooling. One RCT found an almost 30% reduction in the impact of drooling on patients’ lives, as measured by the Drooling Impact Scale (mean difference ?27.45; 95% confidence interval [CI] ?35.28 to ?19.62). There were sufficient data to pool results on one outcome measure, the Drooling Frequency and Severity Scale, which supports this result (mean difference ?2.71; 95% CI ?4.82 to ?0.60; p<0.001). There was a significant reduction in the observed number of bibs required per day. The incidence of adverse events ranged from 2 to 41%, but was inconsistently reported. One trial was terminated early because of adverse events. Interpretation BoNT is an effective, temporary treatment for sialorrhoea in children with cerebral palsy. Benefits need to be weighed against the potential for serious adverse events. More studies are needed to address the safety of BoNT and to compare BoNT with other treatment options for drooling.     

Electrophysiology in chronic inflammatory demyelinating polyneuropathy with IGIV

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) received immune globulin intravenous, 10% caprylate/chromatography purified (IGIV‐C, Gamunex; n = 59) or placebo (n = 58) every 3 weeks for up to 24 weeks (first period) in a randomized, double‐blind, parallel‐group, response‐conditional, crossover study. Motor and sensory nerves were assessed at baseline and endpoint/week 24. A nonsignificant trend toward improvement in the proximal amplitude of the most severely affected motor nerve was observed with IGIV‐C (0.69 ± 1.86 mV) versus placebo (0.47 ± 2.29 mV), and a greater improvement of 1.08 ± 2.15 mV with IGIV‐C versus 0.46 ± 2.03 mV with placebo (P = 0.089) was observed with exclusion of data from Erb's point stimulation. Greater improvements from baseline favoring IGIV‐C were observed for 127/142 electrophysiologic parameters. The averaged motor amplitudes from all motor nerves significantly improved with IGIV‐C versus placebo [treatment difference, 0.62 mV; 95% confidence interval (CI), 0.05, 1.20; P = 0.035], and conduction block decreased significantly (treatment difference, ?5.54%; 95% CI, ?10.43, ?0.64; P = 0.027), particularly in the lower limbs. Overall, the data suggest that IGIV‐C improves electrophysiologic parameters in CIDP. Muscle Nerve, 2009     

Botulinum toxin versus submandibular duct relocation for severe drooling

Aim Botulinum neurotoxin type A (BoNT‐A) has been described as an effective intervention for drooling and is being increasingly adopted. However, its effectiveness compared with established treatments is still unknown. We undertook a within‐participants observational study to examine this. Method An historic cohort was formed of 19 children and young adults (10 males, nine females) with severe drooling who underwent BoNT‐A injections followed by surgical re‐routing of the submandibular duct at least 6 months later. Mean age at time of admission was 11 years 5 months (range 5–17y) and mean age at the time of surgery was 14 years (range 6–23y). Fifteen children were diagnosed with bilateral cerebral palsy (CP), three with unilateral CP, and one with non‐progressive developmental delay. Gross Motor Function Classification System levels were the following: level I, n=1; level II, n=2; level III, n=7; level IV, n=6; and level V, n=3). The primary outcome was the drooling quotient, which was assessed before each intervention and 8 and 32 weeks thereafter. A multivariate analysis of variance of repeated measures was performed, with the measurement points as the within‐participant variables. Results The drooling quotient was reduced to a greater extent after surgery than after BoNT‐A administration (p=0.001). Compared with a baseline value of 28, the mean drooling quotient 8 weeks after surgery was 10, and 32 weeks after surgery was 4 (p<0.001). Among the group treated with BoNT‐A, the drooling quotient showed a significant reduction from a baseline value of 30 to 18 after 8 weeks (p=0.02), and a continued but diminished effect after 32 weeks (drooling quotient 22; p=0.05). Interpretation Both interventions are effective, but surgery provides a larger and longer‐lasting effect.     

Rotigotine effects on early morning motor function and sleep in Parkinson's disease: A double‐blind,randomized, placebo‐controlled study (RECOVER)

In a multinational, double‐blind, placebo‐controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early‐morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early‐morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS‐2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by ?7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by ?3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS‐2 total score had decreased by ?5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by ?1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: ?3.55 [95% confidence interval (CI) ?5.37, ?1.73]; P = 0.0002) and PDSS‐2 (treatment difference: ?4.26 [95% CI ?6.08, ?2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty‐four‐hour transdermal delivery of rotigotine to PD patients with early‐morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. © 2010 Movement Disorder Society     

The relation between conduction velocity and axonal length

Motor evoked potentials (MEPs) obtained by electrical root stimulation and F waves were used to examine the proximal nerve conduction velocity (CV) to tibialis anterior (TA), extensor digitorum brevis (EDB), flexor carpi radialis (FCR), and abductor pollicis brevis (APB) muscles in 40 humans. By subtracting motor latencies obtained by stimulating the peripheral nerve at the same point from the F-wave and MEP latencies, we could measure the CV over identical proximal segments. It was found that proximal CV to TA and FCR was significantly higher than to EDB and APB, respectively. Combining the data of the proximal CV to all four muscles in relation with axonal length resulted in a highly significant inverse relationship (r² = 0.77). Thus the axonal length explained to a large extent the higher CV of the arm nerves and also the inverse relation between body height and CV. The distal CV was always lower than proximal CV; however, there was no support for an additional effect of this gradient in explaining the relationship between CV and height since it was constant for all body heights. © John Wiley & Sons, Inc.     

Levetiracetam for the management of levodopa‐induced dyskinesias in Parkinson's disease

The efficacy and safety of levetiracetam (LEV), administered for management of levodopa‐induced dyskinesias (LID) in Parkinson's disease (PD), was examined using a multicenter, double‐blind, placebo‐controlled, parallel groups, crossover trial. Because of having a period effect, data after crossover point was excluded from analysis. Levodopa‐treated PD participants with LID (n = 38) received LEV 500 mg/day, were assessed, titrated to 1,000 mg/day and reassessed, before and after crossover. The placebo group followed the same routine. Primary efficacy was defined from percent change in “On with LID” time from patient diaries. Secondary efficacy assessment used “On without LID,” “Off” time, unified PD rating scale (UPDRS), clinical global impression (CGI), and Goetz dyskinesia scale after levodopa challenge. Safety measures were also performed. On with LID time decreased 37 minutes (95% confidence interval [CI] 0.59, 7.15; P = 0.02) at 500 mg/day, 7.85% 75 minutes (95% CI 3.3, 12.4; P = 0.002) at 1,000 mg/day. On without LID time increased by 46 minutes (95% CI ?1.55, ?0.03; P = 0.04) at 500 mg/day and 55 minutes (95% CI ?10.39, ?1.14; P = 0.018) at 1,000 mg/day. UPDRS 32 showed decreased dyskinesia duration mean change 0.35 (95% CI 0.09, 0.5; P = 0.009) at 1,000 mg/day. CGI showed LID decreased by 0.7 (95% CI 0.21, 1.18; P = 0.006) at 1,000 mg/day. Patient diaries and UPDRS show no increase in Off time. This exploratory trial provides evidence that LEV in 1,000 mg/day, slowly titrated, could be useful in improving LID as was assessed with patient diaries, UPDRS, and CGI scales, safely, with minimal side effects. © 2010 Movement Disorder Society