Does Motor Performance Matter in Botulinum Toxin Efficacy for Drooling?

The aim of this study was to define factors that influence therapy outcome of submandibular botulinum toxin injections for drooling in children with cerebral palsy or mental disability. We postulated that differences in response may be explained by the variation of dysfunctions in the various cerebral palsy subtypes. Prospectively collected data were evaluated of 80 spastic and 48 dyskinetic children, of whom 70% had an IQ of <70. In addition, the data of 23 fully ambulant children with mental disability only were examined. Flow and Drooling Quotient were assessed at baseline and at 8 weeks after injection. After treatment, both the Drooling Quotient and submandibular flow decreased in all children. Morbidity associated with the procedure was limited. Ninety-three children responded to botulinum. Decrease of submandibular flow in these children was associated with reduction of parotid flow. In those who did not respond to therapy, spread across all 3 diagnostic classifications, parotid flow increased after injection. Response failure is characterized by increased parotid flow after injection; however, the precise role of parotid flow in therapy failure remains unclear. We cannot predict who will respond to botulinum toxin to treat drooling.     

Use of benzhexol hydrochloride to control drooling of children with cerebral palsy

The use of benzhexol hydrochloride to control drooling was evaluated in a group of 20 children with cerebral palsy. Drooling was measured before treatment and then repeatedly until an optimal dosage of benzhexol hydrochloride was attained. 17 of the 20 children showed an improvement in drooling, and side-effects were minimal. This type of medication appears to be useful in the treatment of drooling.     

Repeat botulinum toxin-A injections in the upper limb of children with hemiplegia: a randomized controlled trial

Aim  To test the effectiveness of repeat botulinum toxin A (BoNT‐A) injections in the affected arm of 22 children with hemiplegic cerebral palsy (19 males, three females), aged 1 year 10 months to 4 years 10 months (mean 3y 8mo, SD 9mo) in a randomized controlled trial. Method  Children received either three series of BoNT‐A injections plus twice‐weekly occupational therapy (OT) or OT alone in 16‐week cycles. Muscles targeted at each injection cycle in the 11 children receiving BoNT‐A+OT were the adductor pollicis (n=9), flexor pollicis longus (n=5), flexor digitorum superficialis (n=8), flexor digitorum profundus (n=8), flexor carpi radialis (n=2), flexor carpi ulnaris (n=6), pronator teres (n=10), and biceps brachii (n=11). Parental perception of treatment efficacy was assessed using the Canadian Occupational Performance Measure (COPM) and the Goal Attainment Scale (GAS), quality of movement using the Quality of Upper Extremity Skills Test (QUEST), fine motor skills using the Peabody Developmental Motor Scale – Fine Motor (PDMS‐FM), and spasticity using the Modified Tardieu Scale (MTS). Between‐group differences at 12 months were analysed using independent‐sample t‐tests. Results  All children were at Gross Motor Function Classification System levels I (BoNT‐A+OT n=6; OT n=8) or II (n=5 and n=3 respectively) and were too young to be classified using the Manual Ability Classification System. The BoNT‐A+OT group had higher COPM performance scores (mean difference ?0.8, 95% confidence interval [CI] ?1.5–0.0) and higher GAS T scores (mean difference ?6.9, 95% CI ?13.8 to ?0.1]). No significant difference was found for the COPM satisfaction, PDMS‐FM, or QUEST scores. The BoNT‐A+OT group showed progressive reduction in spasticity compared with the OT group. At study completion MTS mean difference was 50.0° (95% CI 22.4–77.6) for pronators and 20.9° (95% CI 2.4–39.4) for wrist flexors. Interpretation  Repeat BoNT‐A injections in the upper limb combined with OT resulted in progressively reduced spasticity and improved parental perception of performance.     

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.     

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.     

Drooling in children with cerebral palsy: effect of salivary flow reduction on daily life and care

The purpose of this study was to investigate the effect of salivary flow reduction on daily life and provision of care in children with cerebral palsy (CP). Parents of children with CP were asked to fill in a questionnaire on the impact of drooling on the daily life of their children and their families and the data were then analyzed. Forty-five children with severe drooling (28 males, 17 females; mean age 9y 5mo [SD 3y 7mo]; range 3 to 16y) were monitored before and after receiving medication (scopolamine and botulinum toxin) to reduce salivary flow. Type of CP included hypotonia (n = 1), spastic paresis (n = 27), and mixed motor disorders with spastic and dyskinetic paresis (n = 17). Eight children were independently ambulant and 37 children were wheelchair users. Thirty-four children had learning disability with a developmental age of below 6 years. Six participants dropped out of the study; data on 39 children were analyzed. Results showed that anticholinergic agents effectively reduced salivary flow. Drooling diminished substantially and this was accompanied by a significant reduction in care needs, making daily care less demanding. The amount of reported damage to communication devices and computers decreased. In addition to the evaluation of primary variables, such as the salivary flow rate, investigation of impact of drooling on daily life provides useful information about the outcome of treatment for reduction in drooling.     

Prevalence and definition of drooling in Parkinson’s disease: a systematic review

Drooling (saliva loss) is a frequently reported symptom in patients with Parkinson’s disease (PD), but an accurate estimate of the prevalence of drooling is lacking. The aim of this study was to systematically review the prevalence of drooling in published research papers. A systematic PubMed and CINAHL search was done, including studies published until January 2009. Eight studies were found, presenting prevalence rates of drooling based on responses of PD patients to questionnaires. The statistical heterogeneity was highly significant (P < 0.0001), with prevalence rates ranging from 32 to 74%. The pooled prevalence estimate with random effect analysis was of 56% (95% CI 44–67) for PD patients and 14% (95% CI 3–25) for healthy controls; the pooled relative risk (RR) with random effect analysis was 5.5 (95% CI 2.1–14.4). All studies reported data of community dwelling idiopathic PD patients, with a mean age around 65 years and mild PD in 50–60% of the cases. Heterogeneity was mainly caused by differences in definition or frequency of drooling. The highest prevalence rates included nocturnal drooling where others noted only diurnal drooling. Analysis of the data of two studies showed that drooling is reported frequently by 22–26% of the patients. Prevalence rates were lower in milder PD patients. The summarized findings demonstrate that drooling can be present in half of all PD patients. In about a quarter of PD patients, drooling appears to be a frequently occurring problem. We recommend to report drooling in future studies with more detailed consideration of severity, frequency and nocturnal versus diurnal complaints.     

The Drooling Impact Scale: a measure of the impact of drooling in children with developmental disabilities

Aim To describe the development and clinimetric properties of a new scale to evaluate changes in the impact of drooling in children with developmental disabilities. Method After examining the properties of potential items, 10 items were retained for inclusion in the final Drooling Impact Scale. The clinimetric properties of the scale were evaluated using data from two convenience samples of children attending a saliva‐control clinic: a stable group (n=31, 22 males, nine females; mean age 10y 7mo, SD 4y 5mo, range 3y 6mo–18y 3mo; cerebral palsy [CP] n=17, intellectual disability n=10; non‐ambulatory n=13, nonverbal n=12) and an intervention group (n=49, 29 males, 20 females; mean age 11y, SD 3y 6mo, range 3y 4mo–16y 10mo; CP n=31, intellectual disability n=15; non‐ambulatory n=27, nonverbal n=28). To assess validity, changes in scores on the Drooling Impact Scale over time were compared with a carer’s global rating of change using Pearson’s correlations and t‐tests. A concordance correlation coefficient was used to compute the level of agreement between assessments 1 month apart in stable children. Effect size, standardized response mean, Guyatt responsiveness statistic, and an unpaired t‐test were used to estimate responsiveness. Results The correlation between the global rating and change in Drooling Impact Scale scores was 0.69 (p<0.001). The concordance correlation coefficient was 0.85. An effect size of 1.8, standardized response mean of 1.5, Guyatt responsiveness statistic of 1.4, and mean group difference of 23.5 (95% confidence interval 17.4–29.6) were obtained. Interpretation The Drooling Impact Scale is a valid and reliable subjective measure that is responsive to change.     

Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disorders

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.     

Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks

BackgroundBotulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks.MethodsAdults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs).ResultsIn total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by −0.16 and −0.17, respectively, at the end-of-study visit. Subjects’ GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%).ConclusionsData support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks.     

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.     

Prevalence and predictors of drooling in 7‐ to 14‐year‐old children with cerebral palsy: a population study

Aim To establish a prevalence estimate for drooling and explore factors associated with drooling in a population sample of children with cerebral palsy (CP) aged 7 to 14 years living in Victoria, Australia. Method A self‐report questionnaire was used to collect data on drooling from parents of children born between 1996 and 2001, and registered with the Victorian Cerebral Palsy Register. Results A total of 385 children (231 males, 154 females; mean age 10y 9mo [SD 1y 7mo], range 8–14y) were studied. The clinical type and distribution of CP were spastic (341), ataxic (16), dyskinetic (17), hypotonic (10), and unknown (1). Distribution in Gross Motor Function Classification System (GMFCS) levels was I (103), II (98), III (52), IV (63), V (61), and unknown (8). After adjustment for topographical pattern of motor impairment and GMFCS level, 40% were reported to have experienced drooling between 4 years of age and the time of completing the questionnaire. A significantly higher prevalence of drooling was found in children with poor gross motor function and in those with more severe presentations of CP, including poor head control, difficulty with eating, and inability to sustain lip closure (p<0.001 for each). Drooling was shown to be significantly associated with both intellectual disability and epilepsy in this group of children (p<0.001 for both). Interpretation With a prevalence of 40%, drooling is an important comorbidity in CP. It was considered severe in 15% of children. Poor oromotor function was associated with drooling and could be the target of interventions for this under‐researched problem.     

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.     

Botulinum toxin type B for sialorrhoea in children with cerebral palsy: a randomized trial comparing three doses

Aim The aim of the present study was to evaluate the efficacy and safety of three doses of botulinum toxin type B (BoNT‐B) in reducing persistent sialorrhoea in children with cerebral palsy (CP). Method Children with CP and refractory sialorrhoea were randomized to one of four groups: a control group and three experimental groups receiving a low (1500 mouse units [MU]), medium (3000MU), or high (5000MU) dose of BoNT‐B respectively, into bilateral salivary glands. Drooling was measured using the Thomas‐Stonell rating scale, and the weight and the number of bibs used per day were counted in all children at baseline, 4, and 12 weeks after BoNT‐B injection. Results Twenty‐seven children (15 males, 12 females; mean age 7y 10mo, SD 1y 6mo; range 5–15y) were randomized into a control (seven children: four males, three females) and experimental groups receiving low (six children: four males, two females), medium (seven children: four males, three females), and high (seven children: three males, four females) doses of BoNT‐B respectively. All children had mixed neurological disorders consisting of spastic paraparesis, tetraparesis, dystonic movements, and ataxia. Gross Motor Function Classification System levels ranged from III to V, and all children had moderate or severe intellectual disability. Estimated means with their standard errors (SEM) of drooling were at baseline, 4, and 12 weeks respectively, as follows: control group, 12.1 (2.1), 11.9 (2.1), 11.8 (2.2), p for trend 0.992; low dose group, 13.8 (2.3), 11.4 (2.3), 13.9 (2.3), p for trend 0.952; medium dose group, 13.9 (2.1), 6.7 (2.1), 7.1 (2.1) p for trend 0.008; and for the high dose group 14.4 (2.1), 5.0 (2.1), 5.6 (2.1), p for trend 0.002. Side effects included dense saliva, xerostomia, and difficulty in swallowing, and were more frequent in the high‐dose group. Interpretation A 3000MU injection of BoNT‐B into the salivary glands significantly improved the frequency and severity of sialorrhoea in children with CP. The lower dose was ineffective, and the higher dose produced no greater benefit and more side effects.     

Adverse events and health status following botulinum toxin type A injections in children with cerebral palsy

Aim The aim of this study was to assess changes in health status before and after, as well as adverse events after, botulinum toxin type A (BoNT‐A) injections in children with cerebral palsy (CP). Method A total of 334 children (190 male; 144 female) aged 1y 6mo to 19y 4mo (mean 9y 2mo, SD 4y) with CP who were undergoing BoNT‐A injections (596 injection courses in total) were clinically audited over a 16‐month period. Of the 334 children, 62 were classified at Gross Motor Function Classification System (GMFCS) level I, 52 of whom had unilateral CP and 10 of whom had bilateral CP. Eighty‐six children were classified at GMFCS level II, 39 of whom had unilateral CP and 47 of whom had bilateral CP. Forty‐four children were classified at GMFCS level III, two of whom had unilateral CP and 42 of whom had bilateral CP. Sixty‐six of the 334 children were classified at GMFCS level IV and 76 as level V. All the children classified as level IV or V had bilateral involvement. The health status of the children in the month before and a prospective audit of health status and adverse events in the month after BoNT‐A injections were examined in order to assess the effects of the toxin. Results The data gathered for the month before administration of BoNT‐A indicated that children with CP had significant background morbidities. After injection of BoNT‐A, adverse events occurred in 23.2% of children. All adverse events were temporary and there were no deaths. Interpretation The results of this audit indicate that there is insufficient evidence to warrant restriction of the administration of BoNT‐A in children with CP at any GMFCS level in our service.     

Management of drooling for children with neurological problems in Hong Kong

OBJECTIVES: To share our experience in the management of drooling in Hong Kong, to describe the clinical profile of children with this problem, and to report the clinical outcome of oro-motor training. METHODS: Children attending the Drooling Clinic of Alice Ho Miu Ling Nethersole Hospital, Hong Kong between January 2000 and June 2003 were included. Multidisciplinary assessment was performed to ascertain the medical condition, functional status and oro-motor difficulties of each child. Intervention might include optimization of medical condition, oro-motor training and surgery. Severity of drooling was rated by a 10-point visual analogue scale (VAS). The outcome of oro-motor training was assessed by the change in VAS from baseline. RESULTS: Eight children, with a mean age of 11.9 years, were included. Six children suffered from cerebral palsy and two had syndromal diagnoses. All had moderate or severe mental retardation. Poor lip closure, inadequate jaw control and delay in swallowing were common oro-motor difficulties. All children received oro-motor training. The mean duration of follow-up for seven children was 17 months. The mean baseline VAS was 7.1. When compared with the baseline, VAS rating during the training period decreased with a mean difference of 3.0. The difference remained at 1.9 at 4 months after training had stopped. Other functional gains, such as improved sucking and swallowing, were identified. Six caregivers declined surgery. One child improved and did not require surgery. CoNCLUSIONS: Short-term follow-up of oro-motor training suggested beneficial outcome.     

Cerebral palsy after perinatal arterial ischemic stroke

The frequency of cerebral palsy, degree of disability, and predictors of disability were assessed in children in a perinatal arterial stroke database. Risk factors were assessed at the univariate level using the Pearson chi(2) and Fisher exact test and at the multivariate level using logistic regression analysis. Seventy-six of 111 children with perinatal stroke (68%) had cerebral palsy, most commonly hemiplegic (66/76; 87%). Multivariate analysis of the entire cohort showed both delayed presentation (OR,9.96; 95% CI, 3.10-32.02) and male sex (OR, 2.55; 95% CI, 1.03-6.32) were associated with cerebral palsy. In subgroup multivariate analyses: in children with neonatal presentation, bilateral infarcts were associated with triplegia or quadriplegia (OR, 5.33; 95% CI, 1.28-22.27); in children with unilateral middle cerebral artery infarcts, delayed presentation (OR, 10.60; 95% CI, 2.28-72.92) and large-branch infarction (OR, 8.78; 95% CI, 2.18-43.67) were associated with cerebral palsy. These data will aid physicians in planning long-term rehabilitative care for children with perinatal stroke.     

Drooling rating scales in Parkinson's disease: A systematic review

BackgroundDrooling is a clinically relevant non-motor symptom of people with Parkinson's disease (PwP). Several drooling rating scales are available. Nevertheless, the compelling scientific evidence supporting their validity is limited. This study aims to evaluate clinical rating scales for drooling, assessing their characteristics, clinimetric properties, and clinical utility classification.MethodsA systematic review was undertaken. Two reviewers performed independent literature searches using the CENTRAL®, CINAHL®, Embase®, MEDLINE®, SciElo®, and SPEECH BITE® databases. We used consensus-based standards for the selection of health measurement instruments (COSMIN) and the International Parkinson's disease and the Movement Disorders (MDS) criteria to evaluate the included rating scales.ResultsThe following six rating scales were identified: Drooling Impact Scale (DIS), Sialorrhea Scoring Scale (SSS), Drooling Severity and Frequency Scale (DSFS), Drooling Rating Scale (DRS), Sialorrhea Clinical Scale for Parkinson Disease (SCS-PD), and the Radboud Oral Motor inventory for Parkinson's disease – Saliva (ROMP-saliva). The scales had heterogeneous characteristics: (i) not all were created/adapted for PwP; (ii) different dimensions associated with drooling are assessed; (iii) cross-cultural adaptations are limited to some languages. The clinimetric properties showed: (i) target population size limitations; (ii) incomplete reliability analysis; (iii) lack of robust validity; (iv) sensitivity to change not fully explored. Following the MDS criteria, only one tool was classified as “recommended”, the ROMP-saliva.ConclusionsThis review provides information for an adequate selection of a drooling rating scale for clinical and/or research purposes. To date, ROMP-saliva is the only scale with substantial evidence of its clinimetric properties adequacy and data in PwP.     

Efficacy,tolerability and safety of perampanel in children and adolescents with epilepsy: Systematic review and meta-analysis

ObjectivePerampanel (PER) is a novel antiepileptic drug. The efficacy, tolerability and safety of PER in children and adolescents with epilepsy are still unclear. We aimed to study the efficacy and safety of PER in children and adolescents with epilepsy.MethodsWe searched PubMed, Embase and Cochrane Library for relevant literature up to November 2022. Then we extracted the relevant data from eligible literature for systematic review and meta-analysis.ResultTwenty-one studies involving 1968 children and adolescent patients were included. A reduction in seizure frequency of at least 50 percent occurred in 51.5% (95% confidence interval [CI] [47.1%, 55.9%]) of patients. Complete seizure cessation occurred in 20.6% (95%CI [16.7%, 25.4%]). The incidence of adverse events was 40.8% (95%CI [33.8%, 48.2%]). The most common adverse events were drowsiness 15.3% (95% CI [13.7%, 16.9%]), irritability 9.3% (95%CI [8.0%, 10.6%]), dizziness 8.4% (95% CI [7.2%, 9.7%]). The incidence of drug discontinuation due to adverse events was 9.2% (95% CI [7.0%, 11.5%]).ConclusionPER is generally well tolerated and effective in the treatment of epilepsy in children and adolescents. Larger studies are still needed to explore the application of PER in children and adolescents.Risk of bias and limitationThe funnel plot suggests that there may be publication bias in our meta-analysis, and most of the included studies were Asian, so there may be some racial differences.