Changes in severity and impact of drooling after submandibular gland botulinum neurotoxin A injections in children with neurodevelopmental disabilities.

AIMS: To examine changes in objective and subjective drooling severity measures after submandibular botulinum neurotoxin A injection in children with neurodevelopmental disabilities, explore their relationship, and evaluate if clinically relevant responses relate to changes in the impact of drooling. METHOD: This longitudinal, observational cohort study involved 160 children (92 males, 68 females; 3-17y, mean 9y 1mo, SD 3y 6mo) treated between 2000 and 2012 at the Radboud University Medical Center, Nijmegen, the Netherlands. Repeated measures analysis of variance was used to compare the 5-minute Drooling Quotient (DQ5) and Visual Analogue Scale (VAS) for drooling severity pretreatment and posttreatment, and Pearson's rho to assess their association. A parent questionnaire was used to assess drooling impact in responders (defined as ≥50% reduction in DQ5 and/or ≥2 SD reduction in VAS for drooling severity 8wks postintervention) and non-responders. RESULTS: One hundred and twelve children (70%) were responders. Their mean VAS for drooling severity and DQ5 scores were significantly lower 32 weeks postintervention compared to baseline. At baseline, the VAS for drooling severity-DQ5 relationship was 'weak' (rs =0.15, p=0.060), whereas it was 'fair' at 8 weeks (rs =0.43, p=0.000) and 32 weeks (rs =0.30, p=0.000). For responders, a significant change was found regarding the impact of drooling on daily care and social interactions at 8 weeks after intervention; most of these effects were maintained at 32 weeks. INTERPRETATION: A clinically relevant response based on a combination of objective and subjective measures of drooling severity was accompanied by positive changes regarding the impact of drooling on daily care and social interactions. WHAT THIS PAPER ADDS: Botulinum neurotoxin A injection into the submandibular glands reduced drooling severity in 70% of children with neurodevelopmental disabilities. Objective (5-minute Drooling Quotient) and subjective (Visual Analogue Scale for drooling severity) measures correlated 8 and 32 weeks after treatment. Objective and subjective measures complemented each other when changes in drooling severity were assessed. Reduced drooling severity was accompanied by positive changes with regard to the impact of drooling.

Clinical practice: swallowing problems in cerebral palsy.

Cerebral palsy (CP) is the most common physical disability in early childhood. The worldwide prevalence of CP is approximately 2-2.5 per 1,000 live births. It has been clinically defined as a group of motor, cognitive, and perceptive impairments secondary to a non-progressive defect or lesion of the developing brain. Children with CP can have swallowing problems with severe drooling as one of the consequences. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Early attention should be given to dysphagia and excessive drooling and their substantial contribution to the burden of a child with CP and his/her family. This review displays the important functional and anatomical issues related to swallowing problems in children with CP based on relevant literature and expert opinion. Furthermore, based on our experience, we describe a plan for approach of investigation and treatment of swallowing problems in cerebral palsy.

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 5-17 y) and mean age at the time of surgery was 14 years (range 6-23 y). 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.

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 3-17 y, mean age 9 y 10 mo) 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 0.38 mL/min; 24 wks after injection 0.26 mL/min) and drooling quotient (baseline 42.5%; 24 wks 28.80%) were substantially reduced, with a concomitant increase in mucin concentration within 8 weeks after BoNT-A injection (from 0.612 to 1.830 U/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.

Drooling in cerebral palsy: hypersalivation or dysfunctional oral motor control?

AIM: To investigate whether drooling in children with cerebral palsy (CP) in general and in CP subtypes is due to hypersalivation. METHOD: Saliva was collected from 61 healthy children (30 males, mean age 9y 5mo [SD 11mo]; 31 females, mean age 9y 6mo [1y 2mo]) and 100 children with CP who drooled (57 males, mean age 9y 5mo [3y 11mo], range 3-19y; 43 females, mean age 10y 1mo [4y 9mo], range 4-19y), of whom 53 had spastic, 42 had dyskinetic, and five had ataxic CP. Almost all children were affected bilaterally, and 90 of them were at Gross Motor Function Classification System levels III or higher. The saliva was collected by the swab saliva collection method. The intensity of drooling was evaluated using the drooling quotient. RESULTS: No difference was found in the flow rates, age, or sex between healthy children and children with CP who drooled. On additional subgroup analysis, the flow rates of children with dyskinetic CP differed statistically from those of healthy children (submandibular p=0.047, parotid p=0.040). INTERPRETATION: This study supports the finding in previous studies that no hypersalivation exists in children with CP who drool. Dysfunctional oral motor control seems to be responsible for saliva overflow from the mouth, whereas increased unstimulated salivary flow may occur in children with dyskinetic CP as a result of hyperkinetic oral movements.

Validity and reliability of the VOAA-DDD to assess spontaneous hand use with a video observation tool in children with spastic unilateral cerebral palsy.

BACKGROUND: In 2003 new computer software, the VOAA (Video Observations Aarts and Aarts), was designed to score and evaluate two important aspects of spontaneous upper limb use, i.e. overall duration and frequency of specific behaviours. The aim of this study was to investigate the test-retest, interrater and intrarater reliability and the construct validity of a new module, the VOAA-DDD, to determine developmental disregard in children with spastic unilateral cerebral palsy (CP). METHODS: A test-retest design with three raters for reliability and a two-group design for construct validity were used. Subjects were a total of 20 children with spastic unilateral CP equally divided in two age groups (2.5-5 and 5-8 years), and 56 healthy children of the same age groups. Overall duration and frequency of specific behaviours of the affected arm and hand were assessed during a task demanding ('stringing beads') and a task stimulating ('decorating a muffin') the use of both hands. Reliability was estimated by intraclass correlation coefficients (ICCs). Construct validity was assessed by comparing children with CP to healthy children. RESULTS: All ICCs exceeded 0.87. In contrast with healthy children, children with CP used their affected hand less during the 'muffin' task compared to the 'beads' task. Of the children with CP, 90% in the age group of 2.5-5 years and 50% in the age group of 5-8 years showed values exceeding the extreme values of healthy controls, respectively, indicating developmental disregard. CONCLUSION: The VOAA-DDD is a reliable and valid instrument to assess spontaneous use of the affected arm and hand in order to determine developmental disregard in children with spastic unilateral CP.

Physical therapy treatment in children with cerebral palsy after single-event multilevel surgery: a qualitative systematic review. A first step towards a clinical guideline for physical therapy after single-event multilevel surgery.

BACKGROUND: The aim of this study was to review available evidence for physical therapy treatment (PTT) after single-event multilevel surgery (SEMLS), and to realize a first step towards an accurate and clinical guideline for developing effective PTT for children with cerebral palsy (CP) after SEMLS. METHODS: A qualitative systematic review (PubMed, Medline, Embase, CINAHL, and the Cochrane Library) investigating a program of PTT after SEMLS in children aged 4-18 years with CP classified by Gross Motor Function Classification System level I-III. RESULTS: Six articles meeting the inclusion criteria were selected. The selected studies provide only incomplete descriptions of interventions, and show no consensus regarding PTT after SEMLS. Neither do they show any consensus on the outcome measures or measuring instruments. CONCLUSIONS: Based on the results of this literature review in combination with our best practice, we propose a preliminary protocol of PTT after SEMLS.

Generalization and maintenance of a self-management program for drooling in children with neurodevelopmental disabilities: A second case series.

In this case series (n = 10) with a non-concurrent multiple baseline design, a self-management program was shown to be effective during inpatient training in eight participants with oral-motor problems and normal intelligence or mild intellectual disabilities. They were taught to perform a self-management routine and to remain dry for increasing time intervals. In addition, the program provided differential (self-) reinforcement of swallowing, controlling and wiping behavior, explicit formulation of motivational factors, instruction and feedback for parents and teachers, and continued practice after discharge. Generalization of the initial effect to the school setting was demonstrated in seven participants. Follow-up assessments demonstrated maintenance of positive results in four children up to 24 weeks, and for two other participants until 6 weeks after discharge. These results appeared to be relevant to parents and teachers. Teaching parents and teachers to implement the procedure enables them to support the child without professional supervision in the case of relapse.

Effect of multilevel botulinum toxin a and comprehensive rehabilitation on gait in cerebral palsy.

To evaluate the effect of multilevel botulinum toxin A and comprehensive rehabilitation on gait pattern, muscle length, and spasticity, a multicenter randomized trial was performed in 46 children with spastic cerebral palsy who walk with flexed knees. Their mean age was 8.0 years (range 4 to 11 years). They were randomly allocated to the intervention group (multilevel botulinum toxin A and comprehensive rehabilitation) or the control group (usual care). After 6 weeks, a significant treatment effect in the intervention group was observed on: improved knee extension during midstance and terminal swing (7 degrees and 5 degrees , P < 0.01, respectively); hip rotation during terminal swing (4 degrees , P = 0.02); gait score (1.7, P < 0.01); decreased spasticity in hamstrings (11 degrees , P < 0.01), gastrocnemius (6 degrees , P = 0.01), and soleus (5 degrees , P = 0.02); and increased muscle length in hamstrings (9 degrees , P < 0.01) and gastrocnemius (5 degrees , P < 0.01). The improved muscle length was maintained up to 24 weeks. This study demonstrated that multilevel botulinum toxin A and comprehensive rehabilitation improves knee extension during gait, increases muscle length, and decreases spasticity in injected muscles after 6 weeks in children who walk with flexed knees. Although the effect on muscle length was maintained after 24 weeks, the effect on gait and spasticity had disappeared.

Behavioral treatment of drooling: a methodological critique of the literature with clinical guidelines and suggestions for future research.

Many children with mental retardation and developmental disabilities suffer from the consequences of chronic drooling. Behavioral treatment for drooling should be considered before other, more intrusive treatments such as medication and surgery are implemented. However, empirical studies on behavioral procedures are scarce. This article reviews 19 behavioral studies published since 1970. Treatment procedures are (a) instruction, prompting, and positive reinforcement; (b) negative social reinforcement and declarative procedures; (c) cueing techniques; and (d) self-management procedures. Although these procedures yield positive results, critical examination of experimental methodology of the studies reveals several methodological shortcomings. Guidelines for clinical use of behavioral treatment for drooling are presented, and recommendations are given for future research in this area.

A pilot study of the Video Observations Aarts and Aarts (VOAA): a new software program to measure motor behaviour in children with cerebral palsy.

A new computer software program to score video observations, Video Observations Aarts and Aarts (VOAA) was developed to evaluate paediatric occupational therapy interventions. The VOAA is an observation tool that assesses the frequency, duration and quality of arm/hand use in children, in particular those with cerebral palsy. Reliability studies show that the first module, designed to evaluate a forced-use programme, has an excellent content validity index (0.93) and good intra- and inter-observer reliability (Cohen's kappas ranging from 0.62 to 0.85 for the three activities tested). With the built-in statistical package, paediatric occupational therapy departments can conduct therapeutic evaluations with children with impairments in the upper extremities. Further research is recommended to apply the VOAA in clinical studies in paediatric occupational therapy.

Assessment of salivary flow rate: biologic variation and measure error.

OBJECTIVE: To investigate the applicability of the swab method in the measurement of salivary flow rate in multiple-handicap drooling children. To quantify the measurement error of the procedure and the biologic variation in the population. STUDY DESIGN: Cohort study. METHODS: In a repeated measurements design, a baseline series of salivary flow rates were obtained from 45 children. The within-subject SD (SW) was calculated to express the measurements error according to a procedure introduced by Bland and Altman. RESULTS: Two hundred twenty-four samples (mean 0.40 mL/min, SD 0.19 mL/min) were obtained and analyzed. The results of this study indicate that consistent scores were obtained at subsequent measurements, and good parity existed between the two measurements of salivary flow rate at each session. The SW could be estimated (0.11 mL/min), which was applied to quantify the specific variation of the salivary flow rate in our population. CONCLUSION: According to Bland and Altman, the SW, which is a quantification of the measurement error and biologic variation, was found to be a useful tool to evaluate the obtained baseline salivary flow rate measurements. The swab method can be used to evaluate salivary flow rates in drooling children with cerebral palsy during interventional studies that aim to reduce saliva production.

The treatment of drooling by ultrasound-guided intraglandular injections of botulinum toxin type A into the salivary glands.

OBJECTIVE: The aim of the study was to present the background, procedure, and technique of bilateral ultrasound-guided, single-dose injections of botulinum toxin type A (BTX) into the salivary glands in patients with severe drooling. STUDY DESIGN: Clinical trial. METHODS: Initially, an in vitro study was performed to determine the volume of the dilution of BTX required for optimal spreading and to gain insight in the spreading pattern of the fluid in the submandibular gland. Subsequently, patients with severe drooling were included in a clinical study. Salivary flow was measured under standardized conditions, and BTX was injected into the submandibular glands with the patient under general anesthesia and with ultrasound guidance as an outpatient procedure or during a short stay at the daytime care unit. RESULTS: BTX for each gland should be diluted in a volume of 1 to 1.5 mL saline to achieve adequate spreading within the gland and to diminish the risk of diffusion into surrounding structures. With ultrasound guidance, separate structures surrounding the glands and structures within the glandular parenchyma are well recognized and injection errors can be avoided. CONCLUSIONS: With the procedure described, it is possible to accurately inject BTX directly into the glandular parenchyma and to visualize spreading of the fluid in the glandular parenchyma. It is found to be a safe method that guarantees an optimal clinical effect and avoids potentially harmful side effects. We recommend ultrasound guidance if injections of BTX into the salivary glands are considered.

Salivation in healthy schoolchildren.

OBJECTIVE: To obtain reference data on the unstimulated salivary flow rate in healthy 6-11-year-old boys and girls, for use in the treatment of drooling in mentally and physically handicapped children. METHODS: Under standard conditions unstimulated saliva was collected from 62 healthy children using the swab method. Flow rate was determined by calculating the increase in weight of cotton rolls placed in the mouth for 5 min. The influence of the variables age, gender and type of gland were evaluated. RESULTS: No significant difference was found between the flow rate in boys and girls or between the children in this age window. The swab method showed good reproducibility. The right and left parotid glands had equal flow rates of 0.15 ml/min. The flow rate in the floor of the mouth secreted by the submandibular and sublingual glands was 0.32 ml/min. CONCLUSIONS: In healthy children of 6-11 years, age and gender did not influence the salivary flow rate and therefore do not have to be taken in consideration when measuring salivary flow rate. The swab method was reliable, easy to carry out and well-tolerated by the group of schoolchildren.

[The treatment of drooling in children]. / De behandeling van kwijlen bij kinderen.

Undesirable drooling in children is an underexposed problem and difficult to treat, although there are multiple treatment options. A multidisciplinary approach is preferable for the examination and treatment of patients with drooling. The injection of botulinum toxin is the most frequently performed treatment for children who drool, but the effects are temporary. If drooling persists despite conservative treatment, surgical interventions performed by an otolaryngologist may be considered and may offer a more definitive solution.

What could predict effectiveness of Botulinum Toxin to treat drooling: a search for evidence of discriminatory factors on the level of body functions or structures.

BACKGROUND: The treatment of drooling is important to families that experience the daily impact and research to elucidate clinical factors that play a role in the outcome of drooling treatment should be encouraged. AIM: To define clinical factors that influence therapy outcome of submandibular Botulinum Toxin (BoNT-A) injections for drooling. METHODS: Prospectively collected data of 128 children with cerebral palsy were evaluated; 80 spastic and 48 dyskinetic movement disorder, mostly Gross Motor Function Classification System III and higher; over 70% had an IQ <70. In addition, 23 fully ambulant children with exclusively intellectual disability were treated for drooling by ultrasound-guided injections of BoNT-A into the submandibular glands. Salivary flow rates and drooling quotients were measured at baseline and at 8 weeks after injection. Extensive information about the oral motor performance was gathered. Successful clinical response was defined as a 50% reduction of the baseline Drooling Quotient; 85 children were responsive to BoNT-A and 66 children unresponsive. RESULTS: Five nominated clinical factors that possibly could influence saliva reduction (head position, lip seal, voluntary control over the tongue, control of voluntary movement functions, and mental age) did not influence the responsiveness to BoNT-A. INTERPRETATION: Other variables need to be considered to predict the outcome of BoNT-A treatment. This article describes the first attempt to reveal the contribution of body functions and structures to the outcome of BoNT-A submandibular injections.

Modified Constraint-Induced Movement Therapy combined with Bimanual Training (mCIMT-BiT) in children with unilateral spastic cerebral palsy: how are improvements in arm-hand use established?

A recent randomized controlled trial indicated that modified Constraint-Induced Movement Therapy followed by Bimanual Training (mCIMT-BiT) is an effective intervention to improve spontaneous use of the affected upper limb in children with unilateral spastic cerebral palsy (CP). The present study aimed to investigate how the above-mentioned improvements as a result of 8 weeks mCIMT-BiT were established. 52 children with unilateral spastic CP with Manual Ability Classification System (MACS) scores I, II or III and aged 2.5-8 years were randomly allocated to either mCIMT-BiT (n = 28) or Usual Care (UC) (n = 24). Developmental disregard ('learned non-use') and upper limb capacity and performance scores were derived from the Video Observations Aarts and Aarts, module Determine Developmental Disregard. Active and passive range of motion at the affected wrist and elbow were assessed using goniometry during isolated movements. Upper limb capacity and performance demonstrated significantly greater improvements after mCIMT-BiT compared to UC, which lasted up to 8 weeks follow-up, whereas developmental disregard and passive and active range of motion did not show differential effects. The results support the notion that improvement of capacity and performance of the upper limb through mCIMT-BiT in children with unilateral spastic CP is based on a better utilization of existing motor functions of the affected arm and hand. However, enhancement of the overall amount of use (or the reduction of learned non-use) may still be suboptimal leaving room for improvement of this treatment.

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.

Effectiveness of modified constraint-induced movement therapy in children with unilateral spastic cerebral palsy: a randomized controlled trial.

BACKGROUND: In children with unilateral spastic cerebral palsy (CP), there is only limited evidence for the effectiveness of modified constraint-induced movement therapy (mCIMT). OBJECTIVE: To investigate whether 6 weeks of mCIMT followed by 2 weeks of bimanual task-specific training (mCIMT-BiT) in children with unilateral spastic CP improves the spontaneous use of the affected limb in both qualitative and quantitative terms more than usual care (UC) of the same duration. METHODS: Children with unilateral spastic CP with Manual Ability Classification System (MACS) scores I, II, or III and aged 2.5 to 8 years were recruited and randomly allocated to either the mCIMT-BiT group (three 3-hour sessions per week: 6 weeks of mCIMT, followed by 2 weeks of task-specific training in goal-directed bimanual play and self-care activities) or to 1.5 hours of more general physical or occupational weekly plus encouragement to use the affected hand for the UC group. Primary outcome measures were the Assisting Hand Assessment and the ABILHAND-Kids. Secondary outcomes were the Melbourne Assessment of Unilateral Upper Limb Function, the Canadian Occupational Performance Measure, and the Goal Attainment Scale. RESULTS: Twenty-eight children were allocated to mCIMT-BiT and 24 to UC. Except for the Melbourne, all primary and secondary outcome measures demonstrated significant improvements in the mCIMT-BiT group. CONCLUSION: mCIMT followed by task-specific training of goal-directed bimanual play and self-care activities is an effective intervention to improve the spontaneous use of the more affected upper limb in children with relatively good baseline upper extremity function.

Efficacy and duration of botulinum toxin treatment for drooling in 131 children.

OBJECTIVE: To address the efficacy of botulinum toxin and the duration of its effect when used on a large scale for the treatment of drooling in children with neurological disorders. DESIGN: Prospective cohort study. SETTING: Academic multidisciplinary drooling clinic. PATIENTS: A total of 131 children diagnosed as having cerebral palsy or another nonprogressive neurological disorder and who also have moderate to severe drooling. INTERVENTION: Injection of botulinum toxin to the submandibular glands. MAIN OUTCOME MEASURES: Direct observational drooling quotient (DQ) (0-100) and caretaker visual analog scale (VAS) scores (0-100). RESULTS: A clinically notable response was found in 46.6% of children, reflected in a significant mean reduction in DQ from a baseline of 29 to 15 after 2 months and 19 after 8 months (P < .001). The mean VAS score decreased from 80 at baseline to 53 after 2 months and increased to 66 after 8 months (P < .001). Kaplan-Meier analysis showed that patients who initially responded to treatment experienced relapse after a median of 22 weeks (interquartile range, 20-33 weeks). CONCLUSIONS: Our study provides further support for botulinum toxin's efficacy for treatment of drooling in approximately half of patients for a median of 22 weeks. Further optimization of patient selection should be an area of attention in future studies.