Månadens artikel

Berikande miljö

Environmental enrichment intervention for Rett syndrome: an individually randomised stepped wedge trial.

Downs, J., Rodger, J., Li, C., Tan, X., Hu, N., Wong, K., … & Leonard, H. (2018). Environmental enrichment intervention for Rett syndrome: an individually randomised stepped wedge trial. Orphanet journal of rare diseases, 13(1), 3. doi: 10.1186/s13023-017-0752-8.

I artikeln beskrivs vikten av en berikande omgivning för att minska funktionella svårigheter hos personer med Rett syndrom. Utvärdering av specifik medicinsk behandling som påverkar BDNF nivån i blodet diskuteras.

Abstract

Background: Rett syndrome is caused by a pathogenic mutation in the MECP2 gene with major consequences for motor and cognitive development. One of the effects of impaired MECP2 function is reduced production of Brain Derived Neurotrophic Factor (BDNF), a protein required for normal neuronal development. When housed in an enriched environment, MECP2 null mice improved motor abilities and increased levels of BDNF in the brain. We investigated the effects of environmental enrichment on gross motor skills and blood BDNF levels in girls with Rett syndrome.

Methods: A genetically variable group of 12 girls with a MECP2 mutation and younger than 6 years participated in a modified individually randomised stepped wedge design study. Assessments were conducted on five occasions, two during the baseline period and three during the intervention period. Gross motor function was assessed using the Rett Syndrome Gross Motor Scale (maximum score of 45) on five occasions, two during the baseline period and three during the intervention period. Blood levels of BDNF were measured at the two baseline assessments and at the end of the intervention period. The intervention comprised motor learning and exercise supplemented with social, cognitive and other sensory experiences over a six-month period.

Results: At the first assessment, the mean (SD) age of the children was 3 years (1year 1 month) years ranging from 1 year 6 months to 5 years 2 months. Also, at baseline, mean (SD) gross motor scores and blood BDNF levels were 22.7/45 (9.6) and 165.0 (28.8) ng/ml respectively. Adjusting for covariates, the enriched environment was associated with improved gross motor skills (coefficient 8.2, 95%CI 5.1, 11.2) and a 321.4 ng/ml (95%CI 272.0, 370.8) increase in blood BDNF levels after 6 months of treatment. Growth, sleep quality and mood were unaffected.

Conclusions: Behavioral interventions such as environmental enrichment can reduce the functional deficit in Rett syndrome, contributing to the evidence-base for management and further understanding of epigenetic mechanisms. Environmental enrichment will be an important adjunct in the evaluation of new drug therapies that use BDNF pathways because of implications for the strengthening of synapses and improved functioning.

 

Handstereotypier vid Rett syndrom

Pediatric Neurology, 75 (2017) 91-95.

Defining hand stereotypies in Rett syndrome: A movement disorders perspective

Dy, M. E., Waugh, J. L., Sharman, N., O´Leary, H., Kapur, K., D´Gama, A. M., . . . Kaufmann, W. E.

Handstereotyper är ett primärt diagnostiskt kriterium för Rett syndrom. Syftet med studien var att utveckla ett verktyg för att beskriva handstereotypier för att bättre kunna beskriva och mäta dessa i observations- och interventionsstudier. Tre experter bedömde frekvens och typ av handstereotypier utifrån videosekvenser med flickor (2-12 år) med diagnos Rett syndrom. I studien uppnåddes, som högst, endast 50% överensstämmelse mellan experternas bedömning. Författarnas slutsats är att variationen i handstereotypier försvårar en standardiserad bedömning.

Abstract

BACKGROUND

Hand stereotypies (HS) are a primary diagnostic criterion for Rett syndrome (RTT) but are difficult

to characterize and quantify systematically.

METHODS:

We collected video on 27 girls (2-12 years of age) with classic RTT who participated in a mecasermin trial. The present study focused exclusively on video analyses, by reviewing two five-minute windows per subject to identify the two most common HS. Three raters with expertise in movement disorders independently rated the five-minute windows using standardized terminology to determine the level of agreement. We iteratively refined the protocol in three stages to improve descriptive accuracy, categorizing HS as “central” or “peripheral,” “simple” or “complex,” scoring each hand separately. Inter-rater agreement was analyzed using Kappa statistics.

RESULTS:

In the initial protocol evaluating HS by video, inter-rater agreement was 20.7%. In the final protocol, inter-rater agreement for the two most frequent HS was higher than the initial protocol at 50.

CONCLUSION

Phenotypic variability makes standardized evaluation of HS in RTT a challenge; we achieved only 50% level of agreement and only for the most frequent HS. Therefore, objective measures are needed to evaluate HS.

 

Läs- och skrivmetoder

Comprehensive Literacy Instruction, Interprofessional Collaborative Practice, and Students With Severe Disabilities

Erickson, K. A. (2017). Comprehensive Literacy Instruction, Interprofessional Collaborative Practice, and Students With Severe Disabilities. American Journal of Speech-Language Pathology26(2), 193-205.

Praktisk artikel som beskriver metoder för att stödja elever läs- och skrivutvecklingen hos personer med stora funktionsnedsättningar. Bra översikt över metoder från att uppmuntra elever att överhuvudtaget intressera sig för böcker till att lära ut stavning och läsförståelse. 

Abstract:

Purpose: The purpose of this clinical focus article is to briefly describe comprehensive emergent and conventional literacy instruction for students with severe disabilities. Specific attention is given to interprofessional collaborative practice and the roles of team members in planning and delivering instruction.

Method: A rationale for the delivery of comprehensive instruction that balances skill and meaning emphases is provided with reference to new college and career readiness standards, the literature on literacy acquisition for students without disabilities, and, when possible, the literature on literacy acquisition for students with severe disabilities. Specific instructional approaches are presented to demonstrate how teams can actively engage students with severe disabilities in instruction that is collaborative, participatory, and interactive.

Results/Conclusions: Successful provision of comprehensive literacy instruction that allows students with severe disabilities to achieve conventional literacy takes time and the efforts of a collaborative interprofessional team. Speechlanguage pathologists play a critical role on these teams as they ensure that students with severe disabilities have the language and communication supports they need to be successful.

Positivt beteendestöd

Positive behavior support for individuals with behavior challenges

Hieneman, M., Behavior Analysis In Practice. 2015; volume 8, issue 1, pages 108-108 doi: 10.1007/s40617-015-0051-6

Författaren avser att ge en överblick över de principer som utgör kärnan i positivt beteendestöd (PBS). PBS beskrivs som en generell process som samtidigt innehåller tydligt individanpassade komponenter avseende såväl analys som intervention. Principerna åskådliggörs genom en fallbeskrivning som följer den mer akademiska texten.

Abstract:

Individual positive behavior support (PBS) is a process that combines evidence-based practices from applied behavior analysis (ABA) and other disciplines to resolve behavioral challenges and improve independence, participation, and overall quality of life of individuals living and learning in complex community environments. Its features include lifestyle enhancement, collaboration with typical caregivers, tracking progress via meaningful measures, comprehensive function-based interventions, striving for contextual fit, and ensuring buy-in and implementation. This article will summarize the features and illustrate with a case example.

  • Engaging caregivers to take an active role in behavioral intervention
  • Designing interventions that work effectively within natural routines
  • Addressing lifestyle changes, as well as more discrete behavior changes
  • Creating strategies that are durable, reducing dependence on professionals.

 

Epilepsi och sömn vid Angelman syndrom

Epilepsy and sleep disorders improve in adolescents and adults with Angelman syndrome: A multicenter study on 46 patients

Chiara Sueri et al: Epilepsy and Behavior, 2017-10-01, Volume 75, Pages 225-229

Artikeln beskriver epilepsi och sömn över tid hos 46 personer med Angelman syndrom. Epilepsi och i viss mån sömnstörning minskade över tid. Studien indikerar även att det går att minska epilepsimedicinering trots avvikande EEG-mönster. 

 The aim and the method: The purpose of this study was to assess the long term outcome of epilepsy in Angelman syndrome patients (AS), changes in their EEG and sleep problems. This was a retrospective study.

45 Angelman syndrome patients aged 14–45 years were included. The study took place in 3 separate tertiary care centers during a 16 year period. 91.3% of the AS had seizures in infancy/childhood, the seizures improved over the years in all subjects-64% became seizure around age of 10 years. 8/42 had myoclonic status epilepticus during infancy and childhood, 17/42 had tonic–clonic seizures, 6/42 had focal seizures, 15/42 had myoclonic seizures and 12/42 had absence seizures. At the last visit to the tertiary care center 15/42 AS still had epileptic seizures. Cortical tremor was common and persisted, seen in 37/43 of AS at the last visit in the tertiary care center. Valproic acid was the most antiepileptic drug 45% alone/with benzodiazepines, ethosuximide. Some patients had phenobarbital, lamotrigine, levetiracetam and/or topiramate to control their seizures. 84.8% had sleep disorders in childhood, out of which 69% improved over the years. 76.9% of the patients with sleep disorders received treatment during childhood: niaprazine, risperidone, melatonin, pericyazine, levomepromazine, and clonazepam. EEG showed typical Angelman syndrome patterns in 76.1%. Typical awake EEG described meant in this study a) Diffuse theta-delta waves and spike–wave discharges with anterior predominance b) prolonged runs of diffuse mid-voltage theta waves c) spike–wave discharges appearing at eye closure. Slow background activity was evident in 65% of the patients in infancy or childhood and in 54% of the patients during the last visit to the tertiary care center. The typical AS EEG pattern persisted on the last visit the the study center, but 63% AS were seizure-free, 26% had persisting seizures, and 11% never had seizures. During the sleep SWI (spike-wave-index) was higher than in wakefulness.

Conclusion: This study suggests that Angelman syndrome patients have favorable long term outcome with epilepsy and sleep problems also slightly get better. The typical Angelman EEG pattern persists past childhood. Antiepileptic drug withdrawal might be considered despite the persistence of epileptiform abnormalities.

 

Att mäta gång och sittande

Quantification of walking-based physical activity and sedentary time in individuals with Rett syndrome

Downs, J., Leonard, H., Wong, K., Newton, N., & Hill, K. Developmental Medicine & Child Neurology. 2017 Jun;59(6):605-611. doi:10.1111/dmcn.13398. Epub 2017 Feb 6

Artikeln beskriver aktivitetsnivån i gående för olika åldrar

Abstract

Aim: To quantify, in individuals with Rett syndrome with the capacity to walk, walking-based activity and sedentary time, and to analyse the influences of age, walking ability, scoliosis, and the severity of epilepsy.

Sixty-four participants with a mean age of 17 years and 7 months (standard deviation [SD] 9y) were recruited from the Australian Rett Syndrome Database for this cross-sectional study. Each participant wore a StepWatch Activity Monitor for at least 4 days. Linear regression models were used to assess relationships between daily step count and the proportion of waking hours spent in sedentary time with the covariates of age group, walking ability, presence of scoliosis, and frequency of seizures.

Results: On average, 62% (SD 19%) of waking hours were sedentary and 20% (SD 8%) was at cadences lower than or equal to 20 steps in a minute. The median daily steps count was 5093 (interquartile range 2026-8602). Compared with females younger than 13 years of age and accounting for the effects of covariates, adults took fewer steps, and both adolescents and adults had more sedentary time.

Interpretation: Adolescents and adults led the least active lives and would appear to be in particular need of interventions aiming to optimize slow walking-based physical activity and reduce sedentary time.

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Sömn

Sleep in Angelman syndrome: A review of evidence

Spruyt K, et al., Sleep Medicine Reviews (2017), http://dx.doi.org/10.1016/j.smrv.2017.01.002

Abstract

Angelman syndrome-AS, is defined as a neurogenetic disorder with a prevalence of 1:10000–20000 worldwide. The main features are severe intellectual disability, speech impairment, ataxia, epilepsy, sleep disorder and a behavioral phenotype: happy disposition, attraction to or fascination with water and hyper-motoric behavior. The abnormal sleep-wake cycles and diminished need for sleep is a known feature in Angelman syndrome and influences all family members during the day. Caregivers of Angelman syndrome patients report that even up to 72% of individuals with AS have ‘sleep dysfunction’. Angleman sleep studies show that there is reduced sleep duration, increased sleep onset latency, disrupted sleep architecture with frequent nocturnal awakenings, reduced rapid eye movement (REM) sleep and periodic leg movements. The purpose of the present study was to provide information on sleep in individuals with AS.

Methods: Methods of searches, selection of studies, data extraction and quality assessment were specified and limited to Angelman syndrome sleep studies. ‘Sleep’ was categorized into sleep quantity (duration or architecture), sleep quality (problems or disorders), regularity (bedtime schedule, circadian rhythm), sleepiness, sleep hygiene, sleep ecology and sleep treatment. Statistical analyses were performed. Half of the studies were performed in the USA and 42.9% were performed in Europe. The sample size ranged from 1 to 339 individuals with AS (on average 62.35 ± 110.91) within the age-range of 2-44 years. Overall gender was nearly equally distributed, i.e., 49.4 ± 26.23% males.

Results and conclusion: This review and meta-analysis confirms the presence of sleep problems in individuals with AS. Results demonstrated disorders of arousal (nightmares, night terrors and fearful dreams) and sleepiness during the day. The polysomnography studies showed shorter total sleep time, sleep onset latency, wake after sleep onset and poorer sleep efficiency, however short sleep duration and poor sleep efficiency were the most prominent findings. One study reported a higher degree of sleep problems when using anti-convulsant drugs and underlined the role of epilepsy in exacerbating the sleep problems. It was also suggested that low endogenous melatonin levels in individuals with AS. Some individuals loose response to their melatonin treatment whilst high levels of melatonin remain present during the day. Several examples of sleep complaints that may obscure the distinctive feature of an arousal-sleepiness problem are: sleep hyperhidrosis, which may co-occur with an awakening or with regard to the sensitivity to the environment, especially the complaint of ‘is awakened by loud noises’ is prominent. Also ‘unreported’ sleep problems in individuals with AS might excist, like enuresis, bruxism, somnambulism and snoring. Epileptic arousal might also come into question. A thalamocortical dysfunction might excist, resulting from dysregulation of synaptic GABAergic neurotransmission. It was also shown that some part of the problematic sleeping of the individual with AS was associated with poor parental sleep, daytime somnolence and higher parental stress. Therefore a detailed sleep assessment of the individual with AS may benefit the entire family. Future studies need to excel former methodologies (i.e., adept sleep assessment) and more detailed sample descriptions/analysis in order to generate disability-specific sleep problems and treatments in individuals with AS.

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Anfall

Epilepsy and Behavior, 2017, Volume 68, Pages 45-50

Low glycemic index treatment for seizure control in Angelman syndrome-AS: A case series from the Center for Dietary Therapy of Epilepsy at the Massachusetts General Hospital

Grocott, O. R., Herrington, K. S., Pfeifer, H. H., Thiele, E. A., & Thibert, R. L.

Diet med lågt glykemiskt index, GI, är en alternativ kompletterande behandling för behandling av epileptiska anfall vid Angelman syndrom och förefaller också ha andra positiva sidoeffekter för patienterna. 

Abstract

Background: Patients with AS have seizures, abnormally slow EEG background pattern, but also problems with movement, sleep, cognition, gastrointestinal function. The epilepsy can be hard to control with antiepileptic drugs and alternative supportive treatments like ketogenic diet are often necessary. This study discusses about an alternative option (low glycemic index treatment) to ketogenic diet, which might be hard for patients.

The low glycemic index treatment (LGIT), developed by the Center for Dietary Therapy of Epilepsy at the Massachusetts General Hospital (MGH), is similar to the ketogenic diet, but allows for more dietary freedom. The diet does not require a specific meal plan. While the ketogenic diet significantly lowers and controls daily carbohydrate intake, the LGIT aims for an intake of 40-60 g of carbohydrates per day. The carbohydrates must have a low glycemic index that measures the effect of a specific food on blood glucose levels. Foods with higher GI values increase blood glucose levels more than foods with lower GI values.

Methods: The parents completed a three-day food record and a food frequency questionnaire that was used by dietitian to make the goals and suggestions for meals, LGIT guidelines were followed using approximately 40-60 g of low glycemic index (< 50) carbohydrates per day. Recommendations were modified throughout the diet based on the needs and the level of seizure control. The study included 23 subjects with AS aged 2 to 31 years. The majority of subjects (78%) were younger than 10 years of age.

Results: In 5 subjects that had daily seizures, 1 (20%) became seizure-free and the remaining 4 (80%) experienced a decrease in seizures. In 3 subjects that had weekly seizures, 1 (33%) became seizure and the remaining 2 (66%) experienced a decrease in seizures. In 2 subjects that had monthly seizures, 1 (50%) became seizure-free and 1 (50%) became seizure. Benefits from the LGIT other than reduced seizure activity were noted for 13 subjects based on parental reports. Cognitive and social improvements included improved speech, communication, focus, eye contact, receptive speech, alertness, attention, confidence, and general cognitive development. Physical improvements included improved mobility, walking skills, and decreased tremor. One parent also noted improved sleep. Some subjects in our cohort had breakthrough seizures when they consumed too many carbohydrates in one sitting or ate carbohydrates with a high glycemic index, which may suggest maintaining a steady blood glucose level contributes to improved seizure.

The LGIT is an alternative add-on treatment for epileptic seizures in Angelman syndrome and seems to also have many other benefits for the patients

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Glädje och delaktighet

Scandinavian Journal of Occupational Therapy (2016), 23:5, 366-373,
http://dx.doi.org/10.3109/11038128.2015.1130169

Different pathways to children’s enjoyment of participation in daily activities

Rosenberg, L. & Bart, O. Department of Occupational Therapy, School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University.

Upplevelse av glädje från av att delta i aktiviteter i vardagen anses relatera till hälsa och välbefinnande. Studien visar på både barnens- och föräldrars perspektiv. Föräldrarnas perspektiv förknippades med hur väl barnet kunde utföra aktiviteter. Barnens perspektiv av tillfredsställelse och glädje förknippades i högre grad av aktiviteters psykosociala funktion.

Abstract:

Background: The enjoyment arising from participating in an activity is considered to be related to health and well-being. However, only a few studies have focused on children’s enjoyment of participation.

Aim: To assess the contribution of various individual factors to the total explained variance of children’s enjoyment of participation from the perspectives of parents and children.

Methods: Ninety-eight typically developed children were evaluated using motor and cognitive tests; they completed the Children’s Assessment of Participation and Enjoyment. Their parents completed the Children Participation Questionnaire, the Performance Skills Questionnaire, and the Strengths and Difficulties Questionnaire.

Results: Age and gender were found to be significant predictors. Parents perceived enjoyment to be associated with their child’s performance skills and the efficient execution of daily tasks. Children perceived enjoyment to be associated with their psychosocial functioning.

Conclusion: The contribution of performance skills exceeds the contribution of motor or cognitive ability to the total explained variance of a child’s enjoyment of participation. A gap exists, however, between the perspectives of children and parents regarding enjoyment of participation. Enhancing participation is a central goal of the occupational therapy domain and process; our findings may provide insights into possible pathways to accomplish this goal.

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Ögonstyrning

Assistive Technology. 2017; Early online. doi: 10.1080/10400435.2017.1307882

Gaze-controlled communication technology for children with severe multiple disabilities: Parents and professionals’ perception of gains, obstacles, and prerequisites

Holmqvist, E., Thunberg, G., & Peny Dahlstrand, M.

Enligt föräldrar och professionella kan ögonstyrda datorer öppna möjligheter för barn och ungdomar med flera och stora funktionsnedsättningar till inlärning, att kommunicera och delta aktivt. Tekniska problem och praktiska problem upplevdes som hindrande och viktiga förutsättningar var bland annat samarbete mellan familjer och terapeuter och ett motiverande innehåll.

Abstract:

Aim: to explore parents’ and professionals’ thoughts of how a gaze-controlled computer can be beneficial to children with severe multiple disabilities. All systems were provided primarily for symbolbased communication, but were also used for other purposes such as play, leisure and school activities. A further aim was to investigate factors affecting usability, specifically for communication.

Methods: The study used a qualitative approach, involving content analysis of semistructured interviews with the
children’s key persons (N = 11).

Results: The analysis yielded three categories and twelve subcategories. There were
gains for the children in terms of empowerment, social interaction, learning opportunities and efficient
computer use. Inaccessibility, liability issues and technical failure were seen as obstacles, while the
prerequisites included time, collaboration, stimulating content, know-how and opportunities. To sum
up, this study suggests that gaze-controlled technology can provide children who have multiple disabilities
involving severe motor dysfunction and communicative and cognitive problems with new opportunities
to communicate, interact and perform activities independently, as long as conditions are right.

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Andning

Journal of Neurodevelopmental Disorders. 2017; 9: 15. doi: 10.1186/s11689-017-9196-7

Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study

Mackay, J., Downs, J., Wong, K., Heyworth, J., Epstein, A., & Leonard, H.

Andningsstörningar vid Rett syndrom ur ett familjeperspektiv.

Rett syndrome patients are known to have problems concerning autonomic nervous system function. Irregular breathing patterns and abdominal bloating are prominent features, but poorly understood and no studies show good evidence for treatment recommendation. Types of breathing disturbances described in the literature include hyperventilation, breath-holding, central and obstructive apnoea, hypoventilation, apneustic breathing, Valsalva manoeuvres, tachypnoea and periodic breathing.

This study shows the impact and management of these daily symptoms from a caregiver perspective.

Families with Rett Syndrome patients, aged 2-57 years, participated in the study. Web based questionnaries were used to collect data and 413/482 families returned the questionnaries. Mutation types were grouped as C-terminal deletion, early truncating, large deletion, p.Arg106Trp, p.Arg133Cys, p.Arg168*, p.Arg255*, p.Arg270*, p.Arg294*, p.Arg306Cys and p.Thr158Met, and all other pathogenic mutations were grouped as “other”.

Breath-holding was reported for 68.8%, hyperventilation for 46.4% and abdominal bloating for 42.4%. Breathing irregularities start in the early childhood. 63,8% had breath holding at the age of  5 years. This age was not influenced by the mutation type. Hyperventilation and abdominal bloating associated mostly with ap.Arg294* mutation (this mutation normally associates with least severe clinical phenotype). Frequent hyperventilation declined with age, Abdominal bloating was more associated with older age. Hyperventilation was reported in 62.7% of individuals who experienced breath-holding. 48.5% of those with breath-holding experienced abdominal bloating, 57.1% with hyperventilation. They also found that abdominal bloating commonly co-occurred with both hyperventilation and breath-holding. Abdominal bloating had a major impact on the individual’s life in nearly half of those reported to experience the condition and breath-holding/hyperventilation had less impact on an individual’s life. However, the impact of both conditions are still crucial in the daily life.

31 patients got treatment for breathing irregularities. 4 patients on topiramate showed improvement and 2 with acetazolamide, improvement following use of buspirone was not clear. Breathing irregularities seemed to be helped by CPAP/BIPAP. 21 individuals used a product with Magnesium for constipation and were suggested to have some positive impact on breathing as well. Further trials are desperately needed to delineate evidence-based management pathways, but this data suggests that topiramate and magnesium citrate could be of importance in the treatment of breathing abnormalities.

 


Benhälsa

PLoS One. 2016 Feb 5;11(2):e0146824. doi: 10.1371/journal.pone.0146824. eCollection 2016.

Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence.

Jefferson A, Leonard H, Siafarikas A, Woodhead H, Fyfe S, Ward LM, Munns C, Motil K, Tarquinio D, Shapiro JR, Brismar T, Ben-Zeev B, Bisgaard AM, Coppola G, Ellaway C, Freilinger M, Geerts S, Humphreys P, Jones M, Lane J, Larsson G, Lotan M, Percy A, Pineda M, Skinner S, Syhler B, Thompson S, Weiss B, Witt Engerström I, Downs J.

Kliniska guidelines för ökad benhälsa vid Rett syndrom.

Abstract

Objectives: We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians.

Methods: An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions.

Results: Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended.

Conclusion: A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.

 


Longitudinal course of epilepsy in Rett syndrome and related disorders.

Brain. 2016 Dec 21.

Daniel C. Tarquinio, Wei Hou, Anne Berg, Walter E. Kaufmann, Jane B. Lane, Steven A. Skinner, Kathleen J. Motil, Jeffrey L. Neul, Alan K. Percy, Daniel G. Glaze

The present study is a large longitudinal investigation of seizures and epilepsy in Rett syndrome. Participants with clinical Rett syndrome and those with MECP2 mutations without the clinical syndrome were recruited through the Rett Natural History study from 2006 to 2015. 1205 participants were enrolled in the study, 922 had classic Rett syndrome.

The diagnosis of atypical Rett syndrome with a severe clinical phenotype was associated with higher prevalence of epilepsy than those with classic Rett syndrome. Specific MECP2 mutations were not significantly associated with either seizure prevalence or seizure severity. Many clinical features were associated with seizure prevalence (frequency of hospitalizations, inability to walk, bradykinesia, scoliosis, gastrostomy feeding, age of seizure onset and late age of diagnosis were independently associated with higher odds of an individual having epilepsy). This study suggests that the cumulative risk of developing epilepsy is high (∼90% over the lifespan), but the course of seizure occurrence and remission is variable. Three distinct patterns of seizure prevalence emerged in classic Rett syndrome: no seizures throughout the study, the ones with frequent relapse and remission and those who had relentless seizures.

Although 248 of those with classic Rett syndrome and a history of seizures were in terminal remission at last contact, only 74 (12% of those with a history of epilepsy) were seizure free and off anti-seizure medication. Prolonged remission of seizures is less common than in other causes of childhood onset epilepsy. The most common scenarios: a remitting and relapsing tendency, waxing and waning over the lifespan. This study suggested that persistent drug resistant epilepsy without remission is not the most common pattern, it is only 16% of those with classic Rett syndrome.

There is an association between growth and seizure prevalence (i.e. greater height and weight are associated with lower seizure prevalence). Adequate nutrition can improve somatic growth in Rett syndrome markedly and raises the possibility that early nutritional intervention could decrease seizure prevalence in Rett syndrome.

The limation of this study was the absence of systematic EEG documentation of seizures. This study emphasizes the known fact that when the seizures are concluded to be epileptic in origin and anti-seizure drugs are initiated, the side effect profiles of medications should be considered carefully in Rett patients. Medications, which can cause behavioural issues (levetiracetam), anorexia and nephrolithiasis (topiramate), QT interval prolongation (felbamate), or marked sedation (benzodiazepines), should be used with caution. Medication choice in Rett syndrome should be based on accurate semiology, EEG characteristics, and risk/benefit with respect to adverse effects. Video-EEG should be used to help determine the epileptogenic nature of events.

 


Uppmärksamhet

Pediatric Neurology, 57, 22-28. doi:http://dx.doi.org/10.1016/j.pediatrneurol.2016.01.015

Aspects of Attention in Rett Syndrome.

Rose, S. A., Djukic, A., Jankowski, J. J., Feldman, J. F., & Rimler, M. (2016).

Barn med Rett syndrom kunde upprätthålla uppmärksamheten på ett föremål på datorskärmen och relativt snabbt flytta blicken till något som dök upp på skärmen. Däremot flyttade de mer sällan blicken i förväg dit föremålet kunde förväntas dyka upp.

Abstract

Aim: We sought to examine fundamental aspects of attention in children with Rett syndrome, a severely disabling neurodevelopmental disorder caused by spontaneous mutations in the X-linked MECP2 gene. To gauge their attention, we used eye tracking, which bypasses the profound impairments in expressive language and hand use in Rett syndrome.We report two aspects of attention shifting and sustaining basic abilities known to drive cognitive growth.

Methods: Two groups were compared: those with Rett syndrome (N ¼ 20; 3-15 years) and a typically developing comparison group (N ¼ 14; 3-16 years), using a task in which an attractive central stimulus was followed, after a short gap, by a dynamic target presented to one side. Time to shift to the target location (reactive and anticipatory saccades) and time fixating the target were assessed.

Results: Children with Rett syndrome were consistently slower to shift (largely because of fewer anticipations); their reactive saccades were also slower than those of typically developing children, but not significantly so. The Rett syndrome group spent considerable time looking at the target (over 75% of available time), although significantly less so than the typically
developing group.

Interpretation: These findings indicate that children with Rett syndrome could maintain attention on a stimulus and orient relatively quickly to the appearance of a target in the visual field. However, they had difficulty in anticipating predictable events, a difficulty in endogenous attention that is likely to have deleterious implications for executive functioning.

 


Musikterapi i klassrummet

Autism Research and Treatment
Volume 2016 (2016), Article ID 1284790, 8 pages

http://dx.doi.org/10.1155/2016/1284790

A Preliminary Investigation of a Specialized Music Therapy Model for Children with Disabilities Delivered in a Classroom Setting

Jenna Mendelson,1 Yasmine White,2 Laura Hans,3 Richard Adebari,3 Lorrie Schmid,3 Jan Riggsbee,4 Ali Goldsmith,3 Burcu Ozler,3 Kristen Buehne,3 Sarah Jones,3 Jennifer Shapleton,3 and Geraldine Dawson2

Musikterapi som intervention inkluderas allt mer som en strategi för barn med flerfunktionsnedsättningar. Denna studie är en pilot baserad på klassrumsbaserade interventioner.

Abstract

Aim: Music therapy is gaining popularity as an intervention strategy for children with developmental disabilities, including autism spectrum disorder (ASD). This study was a pilot investigation of a classroom-based music-based intervention, Voices Together®, for improving communication skills in children with ASD and children with intellectual disabilities.

Methods: Four local public elementary school special education classrooms, serving 5 children with a classification of autistic disorder and 32 children with intellectual disability without autism, were randomly selected to receive one of two levels of exposure to Voices Together music therapy: “long-term” (15 weeks beginning in January 2015 (Time 1), ) or “short-term” (7 weeks beginning 7 weeks later in February (Time 2), ). Using observational ratings, investigators reliably scored participants live in terms of their level of verbal responsiveness to prompts during three songs featured each week of the program.

Results: Both groups demonstrated increases in verbal responses over time; however, only the long-term group demonstrated significant within-group increases.

Conclusions: Preliminary findings suggest that music therapy delivered in a classroom in 45-minute weekly sessions for 15 weeks can promote improvements in verbal responsiveness among individuals with autism and other developmental disabilities. Findings warrant further investigation into the efficacy of classroom-based music therapy programs.

 


Rett syndrom – 50 år

Pediatr Neurol. 2016; 61:3-10.

Rett syndrome turns 50: Themes from a chronicle: Medical perspectives and the human face of Rett syndrome.

Gabriel M, Ronen MD, Peter L & Rosenbaum MD.

En historisk tillbakablick över 50 år av biologisk forskning, utveckling av klinisk forskning och metodutveckling för personer med Rett syndrom. En kvinnas livshistoria presenteras, vikten av samarbete beskrivs samt behovet av god vård, stöd till självständighet såväl som att glädjas och njuta av livet.

Abstract

Background: Fifty years ago Andreas Rett first described in great detail what came to be known as “Rett syndrome.” Understanding girls and women with this syndrome and their families helped in many ways to revolutionize modern neurodevelopmental medicine. For some people the identification of the genetic underpinning of the syndrome and the ongoing biological research into this condition represented the peak of the scientific accomplishments in Rett syndrome. For others, it was developments in clinical research methodologies that were especially important. Above all, the patient- and family-oriented empathetic and collaborative approach to care by professionals collaborating with families has led to immense achievements, both scientific and humanistic.

Aim: The aim of this narrative was to describe the medical and personal life story of a young woman with Rett syndrome and to offer a history that highlights developments in the unraveling of this condition from its initial recognition to our current understanding.

Conclusion: We believe that much can be learned from the humanistic style of care provision combined with the best possible level of assisted autonomy and life enjoyment of the young woman with Rett syndrome. In addition, the approach to collaborative research by dedicated and often charitable leaders in the field can teach us many important lessons about the ethics of clinical and health services research.

 


Om klinisk variation

Cohort study with 151 Rett patients showing the Clinical variability between Rett phenotypes

Rett syndrome: a wide clinical and autonomic picture.

Pini G, Bigoni S, Congiu L, Romanelli AM, Scusa MF, Di Marco P, Benincasa A, Morescalchi P, Ferlini A, Bianchi F, Tropea D, Zappella M.

Orphanet J Rare Dis. 2016 Sep 29;11(1):132.

Abstract

Aim: Rett syndrome is a Clinical diagnosis and is seen in different forms that have different severity degrees in terms of comorbidities, behaviour, prognosis and involvement of the autonomic nervous system. The present study describes the clinical and autonomic features of the RTT patients who attend the Tuscany Rett Center. This study compares the genotype/phenotype relationship as well.

Mehods: Cohort study included 151 Rett syndrome (RTT) patients with a clinical diagnosis of classical or variant RTT syndrome. Assesments included: severity of the condition with clinical-rating scales (ISS, PBZ), study of autonomic nervous system and genetic analysis. Individuals were classified according to existing forms: Classical RTT and three atypical RTT: Z-RTT, Hanefeld, Congenital.

Results: Z-RTT variant cases showed clinical features (communication, growth, epilepsy and development) well documented by specific ISS items and less severe, if compared to classical RTT and show autonomic disorders, previously not reported in the literature. In this form epilepsy is rarely present. In contrast, Hanefeld variant showed the constant presence of epilepsy which has an earlier onset. In Hanefeld variant the frequency of apneas was rare and, among the cardiorespiratory phenotypes, the feeble type is lacking.

Conclusion: A quantitative analysis of the different autonomic components reveals differences across typical and atypical forms of RTT that leads to a more accurate classification of the groups. In this cohort of RTT individuals, the inclusion of autonomic parameter in the classification leads to an improved diagnosis at earlier stages of development.

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Om föräldrar och mående

Developmental Neurorehabilitation. 2016 Early online. Doi: 10.3109/17518423.2016.1142483. Epub Marc 2016

Change over a 16-month period in the psychological well-being of mothers of girls and women with Rett syndrome.

Cianfaglione, R, Hastings, RP, Felce, D, Clarke, A & Kerr, MP.

Mödrar till döttrar med RTT upplever oftare kronisk oro (anxiety) än mödrar i allmänhet. De rapporterar dock inte mer symptom på depression. Mödrar till RTT hade även positiva uppfattningar relaterade till föräldraskapet. Mödrarnas mående var inte kopplat till grad av symptom hos dottern. Däremot fanns en koppling till om döttrarna hade emotionella bekymmer eller beteendeproblematik. Riktade insatser till föräldrar som minskar emotions- och beteendeproblematik hos personer med RTT skulle kunna ha en positiv påverkan på föräldrars välbefinnande. Föräldrars positiva uppfattningar av föräldraskapet kan också behöva uppmärksammas.

Abstract

Aim: There is an emerging research literature on the experiences of family members of girls and women with Rett syndrome (RTT), but a lack of longitudinal data.

Methods: Fifty mothers whose daughters had RTT were surveyed 16–17 months after an earlier cross-sectional study. Measures completed at both time points focused on maternal positive and negative psychological well-being and their daughters’ behavioral and emotional problems and RTT behavioral phenotype severity.

Results: Maternal stress, anxiety, and depression demonstrated at least moderate levels of stability. Maternal positive perceptions were also moderately stable over 16–17 months. Longitudinal analyses suggested that their daughters’ behavioral and emotional problems rather than RTT behavioral phenotype severity predicted later maternal well-being.

Conclusion: Mothers with RTT daughters experience chronic stress (persisting over time) but also ongoing positive perceptions. Practitioners should recognize positive perceptions and also consider targeted behavioral parent training to reduce behavior problems in individuals with RTT.

 


Om skolios

Dev Med Child Neurol. 2016 Jun; 58 (6):632-8. Doi:10.1111/dmcn.12984. Epub Dec 2015
Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: a cohort study.

Downs J, Torode I, Wong K, Ellaway C, Elliott EJ, Izatt MT, Askin GN, Mcphee BI, Cundy P, Leonard H; Rett syndrome spinal fusion group.

Livslängden hos individer med Rett syndrom och svår tidigt uppträdande skolios kan påverkas positivt av spinal fusion i jämförelse med icke opererade individer med svår skolios.

Abstract

Aim: Scoliosis is a common comorbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome.

Methods: Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood.

Results: After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12-0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06-0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16-1.03; p=0.06).

Interpretation: With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.