A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin®) in cervical dystonia

IncobotulinumtoxinA (Xeomin^®, NT 201), a preparation without accessory (complexing) proteins, has shown comparable efficacy and safety to onabotulinumtoxinA in treating cervical dystonia (CD). This study evaluated the efficacy and safety of repeated incobotulinumtoxinA injections in subjects with CD. Following a ≤20-week placebo-controlled, randomized, double-blind, single-dose main period, subjects could enter a ≤68-week prospective, randomized, double-blind, repeated-dose, flexible-interval (minimum 6 weeks) extension period with 240 U or 120 U of incobotulinumtoxinA (≤5 injections). Outcome measures included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and adverse events (AEs). Of 219 subjects completing the main period, 214 were randomized in the extension period to receive incobotulinumtoxinA 240 U (n = 111) or 120 U (n = 103); 169 subjects completed the extension period, with 90 receiving five injection sessions. Both doses of incobotulinumtoxinA provided statistically significant and clinically relevant improvements in mean TWSTRS-Total, -Severity, -Disability, and -Pain scores, from each injection session to respective 4-week follow-up visits. The most frequently reported AE was dysphagia (240 U: 23.4 %; 120 U: 12.6 %), which did not result in any study withdrawals. There was no impact of injection interval on the incidence of AEs (post hoc analysis). A major limitation of this study was the fixed dose design requested by regulatory authorities, which does not reflect clinical practice. However, repeated incobotulinumtoxinA injections (240 or 120 U; flexible intervals) provided sustained efficacy and were well tolerated, with no unexpected safety risks following repeated injections. The incidence of AEs was similar in subjects requiring repeated injections at shorter intervals (≤12 weeks) compared with those treated using longer intervals (>12 weeks).     

Long-lasting benefits of botulinum toxin type B in Parkinson’s disease-related drooling

Purpose   To investigate the safety, efficacy and effectiveness of botulinum toxin type-B (BTX-B) injections into the parotid glands to reduce drooling in Parkinson’s disease (PD) subjects. Methods   A double-blind, randomised, placebo-controlled study enrolled 36 advanced phase PD subjects who complained of disabling drooling. Patients received either 4000U BTX-B or placebo. Anatomically guided injections were performed. Outcome measures were chosen to assess both the subjective feeling of improvement (i. e. the Drooling Severity and Frequency Scale, DSFS, visuo-analogic ratings of familial distress, VAS-FD, and social distress, VAS-SD) and objective saliva reduction (saliva production over five minutes was checked by weighing dental rolls). The Global Impression Score (GIS) was also applied, rating improvement from 0 to 3. Results   One month after injections, BTX-B patients showed a meaningful improvement in almost all subjective outcomes. Two-way analysis of variance gave a significant time × treatment effect, F-value being 52.5 (p < 0.0001) for DS-FS, 23.2 (p < 0.0001) for VAS-FD, 29 (p < 0.0001) for VAS-SD, and 28.9 (p < 0.0001) for UPDRSADL drooling item score. All BTX-B subjects declared sialorrhea reduction of any kind (moderate for 44.4 % cases, and dramatic for 33.3 % subjects), at variance with 61.1 % controls who denied any benefit from treatment. (Chi-square = 22.9; p < 0.0001). When present, benefits lasted on average 19.2 ± 6.3 weeks in the BTX-B group compared to 6.7 ± 1.4 weeks in controls (T-value: 26.4; p < 0.0001). Conclusions   BTXB represents a safe and efficacious tool for the management of PDrelated drooling, ensuring a longlasting waning of this disabling symptom.     

Is drooling secondary to a swallowing disorder in patients with Parkinson's disease?

Drooling is a common manifestation in Parkinson's disease (PD). It causes psychosocial difficulties and can result in aspiration and chest infection. Previous studies point to an association between swallowing problems and sialorrhea. The aim of this study was to determine if drooling is associated with dysphagia in PD patients. Sixteen PD patients with diurnal drooling were assessed using a modified barium swallowing with videofluoroscopy, and a drooling score. Changes in the oral stage of swallowing were seen in 100% of the patients; and in the pharyngeal stage, in 94% of the patients. The results showed a correlation between the drooling scale score and the level of dysphagia (−0.426; p<0.05). Patients with the worst dysphagia had the worst drooling.     

Randomized,placebo‐controlled trial of incobotulinumtoxina for upper‐limb post‐stroke spasticity

Introduction: Efficacy and safety of incobotulinumtoxinA in post‐stroke upper‐limb spasticity were studied. Methods: Subjects randomized 2:1 to incobotulinumtoxinA (fixed dose 400 U) or placebo, with fixed doses for the primary target clinical pattern (PTCP; flexed elbow, 200 U; flexed wrist, 150 U; clenched fist, 100 U). Doses for non‐primary patterns were flexible within predefined ranges. Results: At week 4, incobotulinumtoxinA led to larger improvements in PTCP Ashworth scale (AS) scores than placebo [least‐squares mean change ± standard error: –0.9 ± 0.06 (n = 171) vs. –0.5 ± 0.08 (n = 88); P < 0.001], and more subjects were PTCP AS responders (≥1‐point improvement) with incobotulinumtoxinA (69.6%) than with placebo (37.5%; P < 0.001). Investigator's Global Impression of Change confirmed superiority of incobotulinumtoxinA vs. placebo (P = 0.003). IncobotulinumtoxinA was associated with functional improvements, as demonstrated in responder rates for Disability Assessment Scale principal target at week 4 (P = 0.007). Adverse events were mainly mild/moderate, and were reported by 22.4% (incobotulinumtoxinA) and 16.8% (placebo) of subjects. Conclusions: IncobotulinumtoxinA significantly improved upper‐limb spasticity and associated disability, and was well‐tolerated. Muscle Nerve 53: 415–421, 2016     

Efficacy and safety of modafinil in patients with idiopathic hypersomnia without long sleep time: a multicenter,randomized, double-blind,placebo-controlled,parallel-group comparison study

BackgroundFew treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time.MethodsThis multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety.ResultsIn total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26–6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred.ConclusionModafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time.Clinical trial registrationJapicCTI; 142539.     

Volume matters: The influence of different botulinum toxin‐A dilutions for sialorrhea in amyotrophic lateral sclerosis

Introduction: We aimed to determine the effect of different botulinum toxin‐A (BTX‐A) dilutions on the treatment efficacy and side effects for amyotrophic lateral sclerosis (ALS) related sialorrhea. Methods: Ten patients were enrolled in the study. BTX‐A dilution for Group A was 100 U in 1 ml of saline, whereas the dilution for Group B was 100 U in 2 ml of saline. Both groups received 20 U of BTX‐A in each parotid gland, and assessments were made by means of the Drooling Impact Scale, items 1 and 3 of the ALS functional rating scale, and visual analog scales for drooling and swallowing function. Results: Although both groups exhibited a similar improvement in drooling, Group B had a mild but significant deterioration in bulbar function that was not evident in Group A. Conclusions: These results suggest that BTX‐A has a safer profile when reconstituted with 1 ml instead of 2 ml of saline. Muscle Nerve, 2013     

Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin®) injections in blepharospasm

IncobotulinumtoxinA (Xeomin^®, NT 201) is a purified botulinum toxin type A free from accessory (complexing) proteins. Previous studies evaluated single sets of incobotulinumtoxinA injections for the treatment of blepharospasm. Individualized injection intervals and other potential determinants of efficacy and safety need to be evaluated in a prospective, longitudinal study. Subjects with blepharospasm who completed a ≤20 weeks double-blind, placebo-controlled main period entered a ≤69 weeks open-label extension period (OLEX) and received ≤5 additional incobotulinumtoxinA treatments at flexible doses (≤50 U per eye) and flexible injection intervals (minimum of 6 weeks). Outcome measures included Jankovic Rating Scale (JRS) (sumscore, severity subscore and frequency subscore), Blepharospasm Disability Index, and adverse events. All 102 subjects who completed the main period entered the OLEX; 82 subjects completed the study, 56 received the maximum five injections. From each injection visit to a control visit 6 weeks later, investigator-rated JRS sumscores and subscores, and patient-rated Blepharospasm Disability Index were significantly improved (p ≤ 0.001 for all). All scores were still significantly improved at trial termination compared with the first injection visit (p < 0.05 for all). The most frequently reported adverse events were eyelid ptosis (31.4 %) and dry eye symptoms (17.6 %). The injection interval had no impact on the incidence of adverse events (post hoc analysis). No subject developed neutralizing antibodies during the study. Repeated incobotulinumtoxinA injections, administered at flexible doses and injection intervals from 6 to 20 weeks according to subjects’ needs, provide sustained efficacy in the treatment of blepharospasm with no new or unexpected safety risks.     

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     

Botulinum toxin type A for drooling in Parkinson's disease: a double-blind, randomized, placebo-controlled study.

To investigate the safety and efficacy of botulinum toxin type A (BoNTX) treatment to reduce sialorrhea in Parkinson's disease (PD), a double-blind, randomized, placebo-controlled study enrolled 32 PD patients complaining of excessive drooling. Patients received either 50 U Botox in each parotid gland or placebo without using ultrasound guidance. Subjects treated with BoNTX experienced a reduction in both drooling frequency and familial and social disability (TimexGroup effect: P<0.01), as well as in saliva production (Time x Group effect: P<0.0001). No adverse events were recorded. BoNTX injections are safe and effective treatment for the management of PD-related drooling.     

Botulinum toxin type-B improves sialorrhea and quality of life in bulbaronset amyotrophic lateral sclerosis

Background Sialorrhea is a disabling problem in bulbaronset amyotrophic lateral sclerosis (ALS). Botulinum toxin (BTX) type A and B have been proposed as alternatives to traditional treatments. Objectives To evaluate the efficacy and safety of BTX type B in the treatment of sialorrhea in patients with bulbar-onset ALS. Methods Open-label prospective study of BTX type B injections in parotids (1000 U) and submandibular (250 U) glands using anatomic landmarks. Primary outcome was rate of responders (improvement > 50% on visual analogue scales (VAS) of severity and disability of sialorrhea) 1 month post-treatment. Other outcomes included subjective (drooling and quality of daily living questionnaires) and objective (cotton roll weights and number of paper handkerchiefs used) evaluations. Safety evaluations included questionnaires regarding brain stem symptoms. Results Sixteen ALS patients were included. At 1 month the rate of responders was 75% with a mean reduction of 70% in severity and disabling VASs. Fifteen patients (94 %) reported some benefit with drooling reduction. In objective measurements there was a reduction over 60 % in saliva production and in the number of handkerchiefs used. Onset of effect occurred within 3 days. Most patients reported better quality of living. The most frequent side-effects were viscous saliva, local pain, chewing weakness and respiratory infection. There were no changes in blood pressure or cardiac rate. At 3 months, there was still a positive effect in all outcomes. All patients except one manifested their willingness to repeat treatment. Conclusions Anatomic guided BTX type B injections seem effective and safe to treat sialorrhea in bulbar-onset ALS.     

Autonomic function,as self-reported on the SCOPA-autonomic questionnaire,is normal in essential tremor but not in Parkinson's disease

ObjectiveTo compare autonomic function of subjects with Parkinson's disease (PD) and essential tremor (ET) relative to controls.BackgroundIt has been reported that patients with PD have autonomic dysfunction while no literature exists regarding autonomic function in ET.MethodsSubjects with PD, ET, and controls had autonomic function measured using the SCOPA-Autonomic questionnaire, with the total and domain scores transformed to a scale of 0–100 points.Results62 subjects with PD, 84 with ET, and 291 controls were included. Women were more prevalent in control (69%) compared to PD (44%) and ET (44%) groups, and mean age was significantly younger in PD (73 yrs) and older in ET (83) compared to controls (81). The mean SCOPA-Aut Total score in PD was significantly higher than controls, with no difference in ET. No autonomic dysfunction was found in any domain in ET but in PD there were significant abnormalities in gastrointestinal, cardiovascular, urinary, and thermoregulatory domains. Individual question data revealed a significantly higher percentage of subjects with dysfunction on 11/23 questions in the PD group but only 1 question (sialorrhea) in the ET group compared with controls.ConclusionAutonomic scores, particularly gastrointestinal, cardiovascular, urinary, and thermoregulatory were increased in patients with PD, as assessed by SCOPA-Aut. Patients with ET did not exhibit autonomic dysfunction, with the exception of sialorrhea.     

Specific adverse effects of antiepileptic drugs — A true-to-life monotherapy study

BackgroundIn patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy.MethodsAll patients ≥ 16 years of age with epilepsy for ≥ 12 months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database.ResultsOut of 841 patients, 438 (61% female, mean age: 44.7 ± 17.1 years) on monotherapy were included in this study. Levetiracetam (n = 151), lamotrigine (n = 167), valproic acid (n = 73), or controlled-release carbamazepine (n = 47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score ≥ 45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands.ConclusionIndividual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.     

Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study

IntroductionThe randomized, double-blind phase (DBP) of the TOLEDO study confirmed the efficacy of apomorphine infusion (APO) in reducing OFF time in PD patients with persistent motor fluctuations despite optimized oral/transdermal therapy. Here we report safety and efficacy results including the 52-week open-label phase (OLP).MethodsAll patients completing the 12-week DBP (including those switching early to open-label treatment) were offered OLP entry. The primary objective was the evaluation of long-term safety of APO.ResultsEighty-four patients entered the OLP (40 previously on APO, 44 on placebo) and 59 patients (70.2%) completed the study. The safety profile of APO was consistent with experience from extensive clinical use. Common treatment-related adverse events (AEs) were mild or moderate infusion site nodules, somnolence and nausea. Fourteen (16.7%) patients discontinued the OLP due to AEs, those involving >1 patient were infusion site reactions (n = 4) and fatigue (n = 2); hemolytic anemia occurred in one case. Reduction in daily OFF time and improvement in ON time without troublesome dyskinesia were sustained for up to 64 weeks. Pooled data for week 64 (n = 55) showed a mean (SD) change from DBP baseline in daily OFF time of −3.66 (2.72) hours and in ON time without troublesome dyskinesia of 3.31 (3.12) hours. Mean (±SD) daily levodopa-equivalent dose decreased from DBP baseline to week 64 by 543 mg (±674) and levodopa dose by 273 mg (±515).ConclusionsThe safety and efficacy of APO infusion were demonstrated with long-term use for persistent motor fluctuations, allowing substantial reductions in oral PD medication.     

Long-term evaluation of open-label pimavanserin safety and tolerability in Parkinson's disease psychosis

IntroductionPimavanserin is a selective 5-HT_2A inverse agonist/antagonist approved for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Results from short-term, placebo-controlled studies demonstrated a positive benefit/risk profile. This multi-year, open-label study assessed long-term safety and tolerability of pimavanserin.MethodsThis was an open-label extension (OLE) study in patients previously completing a double-blind, placebo-controlled study or a previous OLE study. Safety was evaluated from adverse events (AEs), clinical laboratory results, motor symptoms, electrocardiograms (ECG), and mortality. Durability of response was assessed from the Clinical Global Impression-Severity (CGI-S) scale and Caregiver Burden Scale (CBS).ResultsOf 459 participants treated in this OLE study (average age 71.2 years), the median duration of treatment was 454 days. Over the entire study period (approximately 11 years), ≥1 AE occurred in 392 (85.4%) patients; the majority were of mild to moderate intensity, with fall (32.0%), urinary tract infection (19.0%), and hallucination (13.7%) most common. Serious AEs occurred in 188 (41.0%) patients, and an AE leading to study termination or dose discontinuation occurred in 133 (29.0%) patients. Sixty-one patients died, 59 (12.9%) during treatment or within 30 days after the last dose of study drug; the observed mortality rate was 6.45 per 100 patient-years of exposure. Mean scores for the CGI-S scale and CBS generally remained stable for up to 192 weeks (>3.5 years).ConclusionsLong-term treatment with pimavanserin 34 mg once daily demonstrated a favorable benefit/risk profile with no unexpected safety concerns. Mortality rates suggested no increased risk following long-term treatment.     

Ultrasound-Guided Botulinum Toxin Type A Salivary Gland Injection in Children for Refractory Sialorrhea: 10-Year Experience at a Large Tertiary Children's Hospital

BackgroundSialorrhea is problematic for neurologically impaired children, and botulinum toxin A salivary gland injection has been reported as effective in reducing sialorrhea. This article assesses the success and safety of ultrasound-guided weight-based botulinum toxin A injection for the management of sialorrhea in children.MethodsA total of 111 patients (63 males; 48 females; average age 7 years) with refractory sialorrhea were treated with ultrasound-guided botulinum toxin type A salivary gland injections (144 procedures) from July 1, 2004, to July 1, 2014, using a single weight-based protocol. Patient history, procedural records, and clinical follow-up documents were retrospectively reviewed. Clinical data were compared with reported effectiveness and complications using odds ratios.ResultsA total of 144 procedures were performed in 111 patients with refractory sialorrhea. Cerebral palsy was the most common underlying etiology for sialorrhea (29%), whereas others included encephalopathy (5%), anoxic brain injury (4%), and a variety of chromosomal anomalies (5%). There was a 100% technical success rate. Overall treatment effectiveness was 68%. Repeat injections were not associated with increased clinical success. No procedure-related deaths or major complications were identified; the minor complication rate was less than 2%.ConclusionsThe protocol used for ultrasound-guided injection of botulinum toxin A proved to be safe and effective in children suffering from sialorrhea. Image guidance technique may lead to a reduction in rates of adverse events reported in other series. Subsequent procedures do not improve upon initial efficacy.     

Drooling in Parkinson’s disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins

IntroductionBotulinum toxins are a therapeutic option for drooling in Parkinson’s Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD.Methods1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models.Results1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: −0.194 ± 0.61, range: −1.28 to 0.97, 95% CI −0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen’s d: −1.32, CI −1.86 to −0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands.ConclusionsThis study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful.     

Efficacy and safety of incobotulinumtoxinA (NT 201, Xeomin) in the treatment of blepharospasm—A randomized trial

IncobotulinumtoxinA (NT 201, Xeomin) is a highly purified botulinum neurotoxin type A formulation, free from complexing proteins. A randomized, placebo‐controlled, double‐blind trial of efficacy and safety compared incobotulinumtoxinA (up to 50 U per eye) to placebo administered in a single treatment session to patients with blepharospasm. All patients had documented satisfactory response to 2 previous treatments with botulinum neurotoxin type A other than incobotulinumtoxinA and had Jankovic Rating Scale severity subscores ≥ 2. Patients (n = 109) were randomized in a 2:1 ratio to incobotulinumtoxinA or placebo and followed up to 20 weeks; 94% completed the study. A significant difference was observed in the primary efficacy variable (change in Jankovic Rating Scale severity subscore rated by an independent rater 6 weeks following treatment), favoring incobotulinumtoxinA by 1.0 point (95% CI [0.5–1.4]; P < .001). Functional impairment, as measured by the Blepharospasm Disability Index, improved by 0.5 points (95% CI [0.2–0.7]; P = .002) compared with placebo. There was a strong correlation between the 2 scale scores. In addition, all secondary outcome measures favored incobotulinumtoxinA. Patients rated the mean therapeutic effect of incobotulinumtoxinA significantly better than placebo (P < .001). Adverse events were reported in 70.3% of incobotulinumtoxinA patients and 58.8% of placebo patients. Eyelid ptosis (18.9% vs 5.9%), dry eye (18.9% vs 11.8%), and dry mouth (14.9% vs 2.9%) occurred most frequently. Tolerability was rated good/very good by 91.9% of incobotulinumtoxinA versus in 85.2% of placebo patients. In conclusion, incobotulinumtoxinA was well tolerated and was associated with statistically significant and clinically relevant reductions in blepharospasm severity and functional impairment. © 2011 Movement Disorder Society     

Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism.

Drooling is a frequent symptom in Parkinson's disease (PD), occurring in almost 75% of all patients. Although it is now well known that drooling in PD is the result of swallowing difficulties rather than excessive saliva production, few treatments have been developed to reduce it. Clinical studies suggest that botulinum toxin A (BTX) injections into salivary glands are effective in decreasing drooling in PD patients. In this double-blind, placebo-controlled study, 20 patients with parkinsonism (idiopathic PD or multiple system atrophy), were randomly assigned to receive 450 U of BTX (Dysport; Ipsen, Berkshire, UK) or 2 ml of placebo, injected into the parotids and submandibular glands under ultrasonographic guidance. Treatment efficacy and safety were assessed at baseline, 1 week and 3 months after BTX injections using clinical scales (Drooling Severity and Drooling Frequency scales) and side effects surveillance. After treatment, the average secretion of saliva in the BTX group was significantly lower than in the placebo group, as appraised by clinical measurements. No side effects were observed in either group. BTX injection into parotids and submandibular glands, under ultrasonographic guidance, is an effective and safe treatment for drooling in parkinsonism.     

Guillain-Barré syndrome in children – High occurrence of Miller Fisher syndrome in East Asian region

BackgroundGuillain-Barré syndrome (GBS) is a rare acquired immune-mediated polyneuropathy. Updated population-based data concerning paediatric GBS is needed.MethodsPaediatric patients aged below 18 years diagnosed with GBS between 2009 and 2018 in all 11 paediatric departments in Hong Kong were identified from the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. The collected data from medical health records were reviewed by paediatric neurologist from each department. Estimated incidence of paediatric GBS was calculated. We also compared our findings with other paediatric GBS studies in Asia.Results63 subjects of paediatric GBS were identified, giving an estimated annual incidence of 0.62 per 100,000 population. Half of the subjects had acute inflammatory demyelinating polyneuropathy (AIDP) (n = 31; 49.2%), one quarter had Miller Fisher Syndrome (MFS) (n = 16; 25.4%), one-fifth had axonal types of GBS (n = 12; 19.0%), and four were unclassified. Paediatric subjects with axonal subtypes of GBS compared to the other 2 subtypes, had significantly higher intensive care unit (ICU) admission rates (p = 0.001) and longest length of stay (p = 0.009). With immunomodulating therapy, complete recovery was highest in those with MFS (100%), followed by AIDP (87.1%) and axonal GBS (75%). Our study also confirms a higher MFS rate for paediatric GBS in East Asia region and our study has the highest MFS rate (25.4%).ConclusionOur population-based 10-year paediatric GBS study provides updated evidence on estimated incidence, healthcare burden and motor outcome of each subtype of paediatric GBS and confirmed a higher occurrence of paediatric MFS in East Asia.     

Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial

Sialorrhea (drooling) is a common symptom of Parkinson's disease (PD) that can significantly impair a patient's health and quality of life. Fifty-four PD subjects with troublesome sialorrhea were enrolled using a multicenter, randomized, double-blind, sequential-dose escalation design in which subjects received a single intraglandular treatment with botulinum toxin type B (doses of 1,500 Units [0.3 mL]; 2,500 Units [0.5 ml]; or 3,500 Units [0.7 ml]) or placebo. Postinjection, subjects were followed acutely for 4 weeks and long-term for up to 20 weeks. Safety/tolerability, as assessed by adverse events, was the primary outcome measure. Efficacy, as assessed by the Drooling Frequency and Severity Scale and unstimulated salivary flow rate, was secondary. Gastrointestinal-related adverse events occurred more frequently in the active groups versus placebo group (31% vs 7%), with dry mouth being most common (15%). There were no serious adverse events attributed to botulinum toxin type B or discontinuations due to adverse events from treatment. At 4 weeks postinjection, Drooling Frequency and Severity Scale scores significantly improved versus placebo (-1.3 ± 1.3) in a dose-related manner (-2.1 ± 1.2, P = 0.0191; -3.3 ± 1.4, P < 0.0001; -3.5 ± 1.1, P < 0.0001, respectively) and unstimulated salivary flow rates significantly decreased in all active groups versus placebo (P ≤ 0.0009). Furthermore, treated subjects appeared to have more sustained improvement in sialorrhea than placebo subjects. We conclude that intraglandular injection of botulinum toxin type B was safe, tolerable, and efficacious in treating sialorrhea in PD patients. Additional studies are warranted to further confirm the drug's robust efficacy, as well as evaluate its effect with repeated dosing.