Impact of Gastrostomy Placement on Nutritional Status, Physical Health, and Parental Well-Being of Females with Rett Syndrome: A Longitudinal Study of an Australian Population.

OBJECTIVES: To evaluate how age-related trends in nutritional status, physical health, and parental well-being in females with Rett syndrome may be related to gastrostomy placement and to examine the impact of the procedure on mortality. STUDY DESIGN: We included 323 females from the Australian Rett Syndrome Study and analyzed their demographic, genetic, and child and parental health data collected from over 6 waves of follow-up questionnaire between 2000 and 2011. We used mixed-effects models to estimate the association between repeated measures of outcomes and age, gastrostomy placement and their interaction and Cox proportional hazards regression models to estimate relative risks of mortality for individuals with gastrostomy. RESULTS: Nearly one-third (30.3%) of the cases underwent gastrostomy placement. Nutritional status based on weight, height, and body mass index (BMI) improved over time, and BMI was greater in individuals with gastrostomy placement than in those without (adjusted ß = 0.87, 95% CI 0.02-1.73). There was no association between gastrostomy placement and individual's physical health outcomes or parental physical and mental health, nor did the age trend of these outcomes vary by gastrostomy insertion status. Nevertheless, among those at risk of suboptimal weight, the all-cause mortality rate was greater in those who had gastrostomy placement compared with those who had not (hazard ratio 4.07, 95% CI 1.96-8.45). CONCLUSION: Gastrostomy placement was associated with improvement in BMI in females with Rett syndrome, but its long-term impact on individuals and their families is unclear.

Gastrointestinal dysmotility in Rett syndrome.

OBJECTIVES: Through evidence review and the consensus of an expert panel, we developed recommendations for the clinical management of gastroesophageal reflux disease, constipation, and abdominal bloating in Rett syndrome. METHODS: Based on review of the literature and family concerns expressed on RettNet, initial draft recommendations were created. Wherein the literature was lacking, 25 open-ended questions were included. Input from an international, multidisciplinary panel of clinicians was sought using a 2-stage modified Delphi process to reach consensus agreement. Items related to the clinical assessment and management of gastroesophageal reflux disease, constipation, and abdominal bloating. RESULTS: Consensus was achieved on 78 of 85 statements. A comprehensive approach to the assessment of gastroesophageal reflux and reflux disease, constipation, and abdominal bloating was recommended, taking into account impairment of communication skills in Rett syndrome. A stepwise approach to the management was identified with initial use of conservative strategies, escalating to pharmacological measures and surgery, if necessary. CONCLUSIONS: Gastrointestinal dysmotility occurs commonly in Rett syndrome. These evidence- and consensus-based recommendations have the potential to improve care of dysmotility issues in a rare condition and stimulate research to improve the present limited evidence base.

Prevalence, clinical investigation, and management of gallbladder disease in Rett syndrome.

AIM: This study determined the prevalence of cholelithiasis and/or cholecystectomy in Rett syndrome, described gallbladder function in a clinical cohort, and identified recommendations for assessment and management of gallbladder disease. METHOD: The incidence of cholelithiasis/cholecystectomy was estimated from data describing 270 and 681 individuals with a pathogenic MECP2 mutation in the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database respectively. Gallbladder function in 25 females (mean age 16y 5mo, SD 20y 7mo, range 3y 5mo-47y 10mo) with Rett syndrome (RTT) was evaluated with clinical assessment and ultrasound of the gallbladder. The Delphi technique was used to develop assessment and treatment recommendations. RESULTS: The incidence rate for cholelithiasis and/or cholecystectomy was 2.3 (95% confidence interval [CI] 1.1-4.2) and 1.8 (95% CI 1.0-3.0) per 1000 person-years in the Australian and International Databases respectively. The mean contractility index of the gallbladder for the clinical sample was 46.5% (SD 38.3%), smaller than for healthy individuals but similar to children with Down syndrome, despite no clinical symptoms. After excluding gastroesophageal reflux, gallbladder disease should be considered as a cause of abdominal pain in RTT and cholecystectomy recommended if symptomatic. INTERPRETATION: Gallbladder disease is relatively common in RTT and should be considered in the differential diagnosis of abdominal pain in RTT.

Assessment and management of nutrition and growth in Rett syndrome.

OBJECTIVES: We developed recommendations for the clinical management of poor growth and weight gain in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. METHODS: Initial draft recommendations were created based upon literature review and 34 open-ended questions in which the literature was lacking. Statements and questions were made available to an international, multidisciplinary panel of clinicians in an online format and a Microsoft Word-formatted version of the draft via e-mail. Input was sought using a 2-stage modified Delphi process to reach consensus. Items included clinical assessment of growth, anthropometry, feeding difficulties and management to increase energy intake, decrease feeding difficulties, and consideration of gastrostomy. RESULTS: Agreement was achieved on 101 of 112 statements. A comprehensive approach to the management of poor growth in Rett syndrome is recommended that takes into account factors such as feeding difficulties and nutritional needs. A body mass index of approximately the 25th centile can be considered as a reasonable target in clinical practice. Gastrostomy is indicated for extremely poor growth, if there is risk of aspiration and if feeding times are prolonged. CONCLUSIONS: These evidence- and consensus-based recommendations have the potential to improve care of nutrition and growth in a rare condition and stimulate research to improve the present limited evidence base.

Parents of children with disability: Mental health outcomes and utilization of mental health services.

BACKGROUND: Caring for a child with disability may result in stress and difficulties for parents, leading to mental health problems. OBJECTIVE: This study aims to investigate the prevalence of mental health problems, mental health service utilization, and costs in parents of children with disabilities compared to parents of children without disabilities. METHODS: We used data from the Longitudinal Study of Australian Children, a nationally representative sample of children recruited in 2004 with biennial follow-up and linkage to out-of-hospital health service use and billing data for the parents. Descriptive analyses were used to present parental mental health measured using the Kessler 6. Generalized linear models were conducted to examine whether being the parent of a child with disability was associated with higher mental health service utilization and costs compared to those without disability. RESULTS: A total of 4935 children and their parents were included in this study. There was a higher prevalence of mental health problems for parents of children with disabilities compared to those without in all child ages. Regression analyses indicated that parents of children aged 12-17 years with disabilities had significantly higher mental health service utilization and costs compared to parents of children without disabilities (biennial cost difference = $86.37, 95%CI ($15.67-$157.07)). However, these differences were not observed among parents of children aged 4-11 years. CONCLUSION: There are high levels of mental health concerns among parents of children with disabilities in Australia. Mental health interventions are needed to support parents of children aged 4-11 years where there appear to be unmet health needs.

Hip displacement and scoliosis in Rett syndrome - screening is required.

AIM: This study aimed to determine the prevalence of hip displacement and spinal deformity in a clinic population of females with Rett syndrome to define implications for screening and management. METHOD: Age, MECP2 gene status, gross motor function, prevalence of hip displacement, as measured by migration percentage, and spinal deformity, determined by measurement of Cobb angle, were recorded. RESULTS: Thirty-one females with a mean age of 15 years 6 months (SD 5y 4mo) fulfilled a clinical diagnosis of Rett syndrome. Fifteen (48%, 95% confidence interval [CI] 30-67) of the cohort had a hip migration percentage of 30% of more. Eight of the 31 patients (95% CI 12-45) had undergone surgery for the prevention or treatment of hip displacement or dislocation. Twenty-seven of the 31 patients (95% CI 70-96) had a scoliosis, with a Cobb angle of less than 10 degrees; 20 patients (95% CI 45-81) had a Cobb angle greater than 30 degrees. Eleven (95% CI 19-55) patients have required spinal fusion surgery. INTERPRETATION: The prevalence of hip displacement and spinal deformity in a clinic cohort of females with Rett syndrome in Victoria, Australia, was very high. Early, repeated, and consistent clinical and radiological surveillance for hip displacement and spinal deformities is recommended in all young patients with Rett syndrome.

The salivagram in severe cerebral palsy and able-bodied adults.

AIMS: To test the hypothesis that the salivagram is frequently positive in those at high risk of aspiration but negative in individuals at low risk of aspiration lung disease. METHODS: We studied 63 individuals with spastic quadriparetic cerebral palsy (CP), aged 14 months to 16 years (31 females and 32 males), and 20 able-bodied young adult volunteers, aged 19-29 years (17 female and three males) using the salivagram. Twenty millilitres of 99mTc-sulphur colloid in saline was instilled into the pharynx of each subject over 1 h. Aspiration was characterised by the appearance of activity in either lung field. RESULTS: Aspiration was demonstrated by salivagram in 56% of children with CP (95% confidence interval 43% to 68%), compared to 0% of young adults (97.5% one-sided confidence interval 0% to 17%). The difference in frequency is highly significant (P < 0.0006). CONCLUSIONS: The salivagram is frequently positive in those at high risk of aspiration, but frequently negative in those at low risk of aspiration. It may be a useful investigation for the demonstration of aspiration.

Impact of scoliosis surgery on activities of daily living in females with Rett syndrome.

BACKGROUND: Scoliosis is a common orthopaedic complication of Rett syndrome, and surgery is commonly used to reduce asymmetry in cases with severe scoliosis. METHODS: Data from questionnaires administered to caregivers biennially from 2000 to 2006 were used to describe functional skill levels in subjects with Rett syndrome, and within-subject change in 16 subjects with scoliosis surgery were compared with within-subject change in 186 pairs of data from 86 subjects with conservatively managed scoliosis. Postsurgical assessment was conducted after a mean of 17.8 months. RESULTS: Surgery was associated with improved activities of daily living as measured by the WeeFIM for subjects who were wheelchair bound (P = 0.05). Mobility levels, social interaction, communication skills, and the frequency of daytime napping remained similar for the group as a whole. CONCLUSIONS: Improvements in activities of daily living are likely to represent an increase in the quality of life for subjects and caregivers and were mainly found in subjects who were wheelchair bound, indicating that those who were more severely affected were able to benefit from this intervention. LEVEL OF EVIDENCE: Therapeutic study: level III.

Feeding experiences and growth status in a Rett syndrome population.

OBJECTIVES: Feeding difficulties in Rett syndrome are complex and multifactorial. In this study, we describe the feeding experiences in Rett syndrome and examine the factors affecting growth. MATERIALS AND METHODS: Using questionnaire data related to a population-based cohort, ages 2 to 29 years (n = 201), we measured the feeding experiences, growth, and factors affecting growth (enteral nutritional support, mutations, mobility, breath-holding, hyperventilation) in subjects with Rett syndrome. RESULTS: The mean weight, height, and body mass index z scores in subjects with Rett syndrome were below that of their age group and decreased steadily with age. Twenty percent of subjects had enteral nutrition support, and it was more common in the older age group. Those with truncating mutations had significantly less enteral nutrition support than the other mutation groups. Furthermore, those with low mobility had lower mean body mass index z scores than those with higher mobility, and increased frequency of breath-holding and hyperventilation also was associated with lower body mass index z scores. CONCLUSIONS: Routine monitoring of growth should continue to determine the severity of nutritional problems in Rett syndrome. Active nutritional management is recommended to ensure females affected with Rett syndrome have the best opportunity to reach their growth potential.

Rett syndrome: establishing a novel outcome measure for walking activity in an era of clinical trials for rare disorders.

BACKGROUND: Rett syndrome is a pervasive neurological disorder with impaired gait as one criterion. This study investigated the capacity of three accelerometer-type devices to measure walking activity in Rett syndrome. METHODS: Twenty-six participants (mean 18 years, SD 8) wore an Actigraph, ActivPAL and StepWatch Activity Monitor (SAM) during a video-taped session of activities. Agreement was determined between step-counts derived from each accelerometer and observation. Repeatability of SAM-derived step counts was determined using pairs of one-minute epochs during which the same participant was observed to walk with the same cadence. RESULTS: The mean difference (limit of agreement) for the Actigraph, ActivPAL and SAM were -41 (SD 33), -16 (SD 21) and -1 (SD 16) steps/min, respectively. Agreement was influenced by a device/cadence interaction (p < 0.001) with greater under-recording at higher cadences. For SAM data, repeatability of step-count pairs was excellent (intraclass correlation coefficient 0.91, 95% CI 0.79-0.96). The standard error of measurement was 6 steps/min and we would be 95% confident that a change ≥17 steps/min would be greater than within-subject measurement error. CONCLUSIONS: The capacity of the SAM to measure physical activity in Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials. Implications for Rehabilitation Many girls and women with Rett syndrome are able to walk on their own or with assistance but with altered movement patterns. Validated measures of physical activity, such as step counts, have potential to monitor function during daily life. Compared with other forms of accelerometer-type devices, such as ActiGraph and ActivPAL, the StepWatch Activity Monitor (SAM) measured step counts with good accuracy and repeatability. The capacity of the SAM to measure physical activity in Rett syndrome allows focus on participation-based activities in clinical practice and clinical trials.

Guidelines for management of scoliosis in Rett syndrome patients based on expert consensus and clinical evidence.

STUDY DESIGN: Modified Delphi technique. OBJECTIVE: To develop guidelines for the clinical management of scoliosis in Rett syndrome through evidence review and consensus expert panel opinion. SUMMARY OF BACKGROUND DATA: Rett syndrome is a rare disorder and clinical expertise is thus with small case series. Scoliosis is a frequent association and the evidence base dealing with scoliosis management in this syndrome is limited. Parents of affected girls and women have expressed needs for more information about scoliosis and Rett syndrome. METHODS: An initial draft of scoliosis guidelines was created based on literature review and open-ended questions where the literature was lacking. Perspectives of four parents of Rett syndrome patients informed this initial draft. Access to an online and a Microsoft Word formatted version of the draft were then sent to an international, multidisciplinary panel of clinicians via e-mail with input sought using a 2-stage modified Delphi process to reach consensus agreement. Items included clinical monitoring and intervention before the diagnosis of scoliosis; monitoring after the diagnosis of scoliosis; imaging; therapy and conservative management; bracing; and preoperative, surgical, and postoperative considerations. RESULTS: The first draft contained 71 statements, 65 questions. The second draft comprised 88 items with agreement to strong agreement achieved on 85, to form the final guideline document. A comprehensive, life-span approach to the management of scoliosis in Rett syndrome is recommended that takes into account factors such as physical activity, posture, nutritional and bone health needs. Surgery should be considered when the Cobb angle is approximately 40 degrees to 50 degrees and must be supported by specialist management of anesthesia, pain control, seizures, and early mobilization. CONCLUSION: Evidence- and consensus-based guidelines were successfully created and have the potential to improve care of a complex comorbidity in a rare condition and stimulate research to improve the current limited evidence base.

Awake upper airway obstruction in children with spastic quadriplegic cerebral palsy.

OBJECTIVE: Some children with severe cerebral palsy develop symptoms of upper airway obstruction (UAO) while awake. The aetiology, natural history and treatment of this complication have not previously been systematically described. This study documents a case series of children with severe cerebral palsy admitted to hospital because of severe awake UAO and reviews the relevant literature. METHODS: The case records of children admitted to hospital with UAO while awake over an 8-month period were reviewed. Details of antecedent illness, comorbidities, acute management and follow up were collated. One case is presented in detail. RESULTS: Eight children were admitted with UAO. Seven children required intensive care admission. One child died, and two underwent tracheostomy. Nasendoscopy showed pharyngeal collapse without anatomical obstruction in the majority. One child was discovered to have a brainstem malignancy. CONCLUSIONS: Upper airway obstruction is a potentially severe and life-threatening complication of cerebral palsy. In this series, a majority of children had obstruction related to pharyngeal hypotonia and collapse. This can lead to prolonged hospitalization and intensive care admission. It may raise difficult management issues.