Clinical aspects of a large group of adults with Angelman syndrome

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe

Determining frailty in people with intellectual disabilities in the COVID-19 Pandemic

Background: Across the world, frailty is part of the guidelines that are being developed in the COVID-19 pandemic for triaging in crisis situations. The Clinical Frailty Scale (CFS) evaluates the ability to perform daily tasks to identify frail individuals, potentially excluding those from intensive care (IC) treatment. Individuals with intellectual disabilities (ID) experience varying degrees of dependence, distinct from age-related physical deterioration. Using the CFS for triage in crisis situations could potentially unjustifiably exclude individuals with ID from IC treatment. Our objective was to compare the classification of individuals with ID into different frailty categories based on the CFS and the well-studied ID-frailty index and to determine suitability of CFS for evaluation of frailty in individuals with ID during the COVID-19 pandemic. Methods: This retrospective analysis of the observational healthy aging and intellectual disabilities (HA-ID) study included 982 individuals with ID of ≥50 years, who were classified according to the CFS and the ID-frailty index. Results: Of the cohort of 982 older adults with ID, 626 (63.7%) would be classified as moderately frail (CFS score 6), but 92% of this group is not moderately frail according to the ID-frailty index. Furthermore, 199 (20.3%) would be classified as at least severely frail (CFS score 7-9), but 74.9% of this group is not severely frail according to the ID-frailty index. Overall, 730 out of 982 (74.9%) individuals would be incorrectly classified by the CFS as too frail to have a good probability of survival. The ID-frailty index predicts mortality better than the CFS in individuals with ID. Conclusions: Our results show the CFS is not suitable to evaluate frailty in individuals with ID, with potential dramatic consequences for triage and decision-making during the COVID-19 pandemic. We strongly recommend using the ID-frailty index when assessing probability of survival for individuals with ID

Prevalence of swallowing difficulties and associated factors in older people with intellectual disabilities

Background: We investigated the prevalence of swallowing difficulties and associated factors in people with intellectual disability. Methods: We included people aged 50+ receiving care for people with intellectual disabilities. The Dysphagia Disorder Survey (DDS) was used to assess swallowing difficulties. We determined the agreement between the DDS and swallowing difficulties in medical records. We used logistic regression analyses to explore associated factors. Results: One thousand and fifty people were included. The prevalence of swallowing difficulties was 43.8%. Swallowing difficulties were not reported in the medical records of 83.3% of these cases. Frailty (odds ratio (OR) = 4.22, 95% CI = 2.05–8.71), mobility impairment (OR = 2.50, 95% CI = 1.01–6.19), and mealtime dependency (OR = 3.05, 95% CI = 1.10–8.47) were independently associated with swallowing difficulties. Conclusion: Swallowing difficulties are prevalent in older people with intellectual disability but may be under-recognised. Frailty may be a good indicator for population-based screening for swallowing difficulties.</p

Reliability and validity of the Dutch Anxiety, Depression And Mood Scale in adults aged <50 years with intellectual disabilities

Background Reliable and valid screening instruments for depression and anxiety are needed for adults with intellectual disabilities. Methods Internal consistency (n = 198), inter-rater reliability (n = 41), test-retest reliability (n = 37) and criterion validity (n = 43) were studied in adults aged between 18 and 49 years. Internal consistency was also studied in a sample with epilepsy (n = 98). Results Internal consistencies of the Dutch ADAMS total scale and subscales were satisfactory to good (alpha = 0.76-0.92), as well as in the subgroup with epilepsy (alpha = 0.74-0.88). Inter-rater reliability and test-retest reliability were fair to excellent for the total scale (ICC's: 0.57-0.84) and subscales (ICC's: 0.43-0.86). The criterion validity of the Dutch ADAMS Depressive Mood subscale was good with a sensitivity of 88% (95% CI: 53%-98%) and a specificity of 80% (95% CI: 64%-90%). Conclusions Our study shows that the Dutch ADAMS is a reliable and valid instrument for adults aged between 18 and 49 years with intellectual disabilities (and comorbid epilepsy)

Are we still in the dark? A systematic review on personal daily light exposure, sleep-wake rhythm, and mood in healthy adults from the general population

Insufficient light exposure is assumed to be related to a wide array of health problems, though few studies focus on the role of whole-day light exposure in the habitual setting in the development of these health problems. The current review aims to describe the association between personal light exposure in the habitual setting and sleep-wake rhythm and mood in healthy adults from the general population. Five databases (Embase, Medline Epub, Web of Science, PsycINFO, and Google Scholar) were searched in June 2019. The inclusion criteria included: assessment directly of light exposure on the participants for at least one full day; reporting on both individual personal light exposure and outcomes. The quality of the papers was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung and Blood Institute. The current review followed the PRISMA guidelines. In total, 8140 papers were identified in the database search. Twenty-five papers were eventually included in this review. All included studies were cross-sectional, and individual light exposure was usually measured with a wrist-worn device. Five studies received a "good" quality rating, 16 received a "fair" rating, and the remaining 4 a "poor" quality rating. The overall quality of the included studies was considered low because of the lack of intervention studies and the fact that light exposure was measured on the wrist. Given the low quality of the included studies, the current review can only provide a first exploration on the association between light exposure and sleep-wake rhythm and mood in healthy adults from the general population. Limited evidence is presented for a positive relationship between the amount and timing of light exposure on the one hand and rest-activity rhythm and some estimates of sleep architecture on the other. The evidence on an association between light exposure and circadian phase, sleep estimates, sleep quality, and mood is conflicting. Data from intervention studies are needed to gain insight into the causal mechanism of the relationship between light exposure and sleep-wake rhythm and mood

Efficacy and tolerability of brivaracetam in patients with intellectual disability and epilepsy

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV). Data on efficacy and tolerability were retrospectively collected. After the initial start of BRV in our tertiary epilepsy center, we analyzed medical records at 0, 3, 6 and 12 months of follow-up. 116 patients were included (mean age = 34.9 years, 44% female). All had complete data of 3-month follow-up, 76 of 6-month follow-up, and 39 patients of 1-year follow-up. Median starting dose of BRV was 50.0 mg/day and the mean number of concomitant AEDs was 2.6. Seizure reduction and no side effects were reported in more than half of all patients. The most reported side effects were somnolence, dizziness and aggression. Retention rates for BRV were 84.4%, 75.5% and 58.1% after 3, 6 and 12 months, respectively. Seizure reduction and side effects did not differ significantly between the groups with or without previous LEV treatment. We demonstrate that BRV is effective and well tolerated in patients with epilepsy and ID, even in those where previous LEV treatment failed

Clinical aspects of a large group of adults with Angelman syndrome

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe the evolution of the clinical phenotypes of AS in adulthood, using clinical data from 95 individuals (mean age 31.6 years, median 29.0 years, range 18–83 years), with genetically confirmed AS. Data was collected through physical examination and inspection of medical records, combined with questionnaires and interviews. Adults with AS experience substantial debilitating health problems. Constipation, reflux, visual problems, scoliosis, behavioral and sleeping problems occurred frequently and require appropriate attention. Epilepsy was reported in 57% of adults, negatively affecting the level of functioning. Non-convulsive status epilepticus was not observed in the adults, however some individuals developed prolonged episodes of rhythmic shaking while awake. A decline in mobility was noted in the majority of adults. A minority of adults with AS showed microcephaly. Taken together, this first phenotypic study of adults with AS to include in person interviews with care-givers and physical examination of patients, including the eldest adult reported to date, provides important insight in the development of the syndrome into adulthood. This knowledge is required to improve care for adult individuals with AS and to evaluate future therapies for this group

Randomized controlled trial to investigate the effects of growth hormone treatment on scoliosis in children with Prader-Willi syndrome.

Item does not contain fulltextCONTEXT: The prevalence of scoliosis in children with Prader-Willi syndrome (PWS) is 30-80%, depending on age. Although reports about effects of GH treatment on scoliosis in children with PWS are limited, scoliosis is generally considered a contraindication for GH treatment. OBJECTIVE: The aim was to study the effects of GH treatment on the onset of scoliosis and curve progression in children with PWS. DESIGN: We conducted a multicenter, randomized, controlled GH study in infants and prepubertal and pubertal children. Infants and prepubertal children were randomized into a GH-treated group (1.0 mg/m(2) . d) and a control group for 1 and 2 yr, respectively. Pubertal children were randomized to receive somatropin 1.0 or 1.5 mg/m(2) . d. Yearly, x-rays of the spine were taken, and height, weight, truncal lean body mass (with dual energy x-ray absorptiometry), and IGF-I were measured. PATIENTS: A total of 91 children with PWS (median age, 4.7 yr; interquartile range, 2.1-7.4) participated in the study. MAIN OUTCOME MEASURES: We measured the onset of scoliosis (Cobb >10 degrees ) and scoliotic curve progression. RESULTS: GH-treated children had similar onset of scoliosis and curve progression as randomized controls (P = 0.27-0.79 and P = 0.18-0.98, respectively). GH treatment, IGF-I sd score (SDS), and catch-up growth had no adverse effect on the onset of scoliosis or curve progression, even after adjustment for confounders. Height SDS, truncal lean body mass, and IGF-I SDS were significantly higher in GH-treated children than in randomized controls. At baseline, a higher IGF-I SDS was associated with a lower severity of scoliosis. CONCLUSIONS: Scoliosis should no longer be considered a contraindication for GH treatment in children with PWS

High prevalence of central adrenal insufficiency in patients with Prader-Willi syndrome.

Item does not contain fulltextCONTEXT: The annual death rate of Prader-Willi syndrome (PWS) patients is very high (3%). Many of these deaths are sudden and unexplained. OBJECTIVE: Because most deaths occur during moderate infections and PWS patients suffer from various hypothalamic insufficiencies, we investigated whether PWS patients suffer from central adrenal insufficiency (CAI) during stressful conditions. DESIGN: Overnight single-dose metyrapone tests were performed. Metyrapone (30 mg/kg) was administered at 2330 h. At 0400, 0600, and 0730 h, ACTH, 11-deoxycortisol, cortisol, and glucose levels were measured. Diurnal salivary cortisol profiles were assessed on a different day at wake-up, 30 min after wake-up, at 1400 h, and at 2000 h. SETTING: The study was conducted in a pediatric intensive care unit. PATIENTS: Patients included 25 randomly selected PWS patients. MAIN OUTCOME MEASURE: Patients were considered as having CAI when ACTH levels remained below 33 pmol/liter at 0730 h. RESULTS: Median (interquartile range) age was 9.7 (6.8-13.6) yr. Fifteen patients (60%) had an insufficient ACTH response (CAI, P < 0.001). There was no significant difference in age, gender, genotype, and body mass index SD score between patients with CAI and those without. Morning salivary cortisol levels and diurnal profiles were normal in all children, suggesting that CAI becomes apparent only during stressful conditions. CONCLUSIONS: Strikingly, 60% of our PWS patients had CAI. The high percentage of CAI in PWS patients might explain the high rate of sudden death in these patients, particularly during infection-related stress. Based on our data, one should consider treatment with hydrocortisone during acute illness in PWS patients unless CAI has recently been ruled out with a metyrapone test