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Journal of Neuroscience Research Feb 2021Due to the discovery of Rett Syndrome (RTT) genetic mutations, animal models have been developed. Sleep research in RTT animal models may unravel novel neural mechanisms...
Due to the discovery of Rett Syndrome (RTT) genetic mutations, animal models have been developed. Sleep research in RTT animal models may unravel novel neural mechanisms for this severe neurodevelopmental heritable rare disease. In this systematic literature review we summarize the findings on sleep research of 13 studies in animal models of RTT. We found disturbed efficacy and continuity of sleep in all genetically mutated models of mice, cynomolgus monkeys, and Drosophila. Models presented highly fragmented sleep with distinct differences in 24-hr sleep/wake cyclicity and circadian arrhythmicity. Overall, animal models mimic sleep complaints reported in individuals with RTT. However, contrary to human studies, in mutant mice, attenuated sleep delta waves, and sleep apneas in non-rapid eye movement sleep were reported. Future studies may focus on sleep structure and EEG alterations, potential central mechanisms involved in sleep fragmentation and the occurrence of sleep apnea across different sleep stages. Given that locomotor dysfunction is characteristic of individuals with RTT, studies may consider to integrate its potential impact on the behavioral analysis of sleep.
Topics: Animals; Brain; CRISPR-Cas Systems; Disease Models, Animal; Drosophila melanogaster; Epileptic Syndromes; Female; Gene Editing; Gene Knock-In Techniques; Humans; Macaca fascicularis; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Mutant Strains; Mutation; Rett Syndrome; Sleep Stages; Sleep Wake Disorders; Spasms, Infantile; Species Specificity
PubMed: 32985711
DOI: 10.1002/jnr.24730 -
Brain Sciences Jun 2020Rett syndrome is a rare genetic disorder that affects brain development and causes severe mental and physical disability. This systematic review analyzes the most recent... (Review)
Review
Rett syndrome is a rare genetic disorder that affects brain development and causes severe mental and physical disability. This systematic review analyzes the most recent evidence concerning the role of physical therapy in the management of individuals with Rett syndrome. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 17319 studies were found in the main scientific databases. Applying the inclusion/exclusion criteria, 22 studies were admitted to the final phase of the review. Level of evidence of the included studies was assessed using the Oxford Centre for Evidence-Based Medicine-Levels of Evidence guide. Nine approaches to physical therapy for patients with Rett syndrome were identified: applied behavior analysis, conductive education, environmental enrichment, traditional physiotherapy with or without aids, hydrotherapy, treadmill, music therapy, computerized systems, and sensory-based treatment. It has been reported that patients had clinically benefited from the analysed approaches despite the fact that they did not have strong research evidence. According to the results, a multimodal individualized physical therapy program should be regularly recommended to patients with Rett syndrome in order to preserve autonomy and to improve quality of life. However, more high-quality studies are needed to confirm these findings.
PubMed: 32630125
DOI: 10.3390/brainsci10070410 -
Journal of Applied Research in... Sep 2020Research into Rett syndrome has included various medical interventions. Non-medical interventions are relatively under-researched. Recent technological communication... (Review)
Review
BACKGROUND
Research into Rett syndrome has included various medical interventions. Non-medical interventions are relatively under-researched. Recent technological communication intervention advances have contributed to the evidence base in Rett syndrome.
METHOD
The Embase, PsycINFO and MEDLINE were systematically searched for peer-reviewed papers describing non-medical interventions for Rett syndrome. All identified papers were evaluated for methodological quality.
RESULTS
Thirteen studies of adequate methodological quality were reviewed (across N = 60 participants). Interventions were primarily communication interventions including music, assistive technology, augmentative and alternative communication strategies, attentional training and cognitive rehabilitation training. All studies reported positive outcomes across communication, quality of life, brain stem activity, physical fitness and a reduction in stereotyped behaviour. However, methodological challenges to generalizability, standardization, lack of follow-up and/or small-N samples were common.
CONCLUSIONS
The review highlights the paucity of high-quality research. Future research is needed to build on current research and improve validity and generalizability of interventions.
Topics: Humans; Intellectual Disability; Quality of Life; Rett Syndrome
PubMed: 31833197
DOI: 10.1111/jar.12694 -
Clinical Neurophysiology : Official... Jan 2020Systematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of...
OBJECTIVE
Systematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).
METHODS
Pubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.
RESULTS
ERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.
CONCLUSIONS
While there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.
SIGNIFICANCE
The review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.
Topics: Age Factors; Animals; Auditory Cortex; Biomarkers; Disease Models, Animal; Electroencephalography; Electroencephalography Phase Synchronization; Evoked Potentials, Auditory; Evoked Potentials, Somatosensory; Evoked Potentials, Visual; Female; Hippocampus; Humans; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Knockout; Mutation; Perceptual Masking; Rett Syndrome; Signal-To-Noise Ratio; Visual Cortex
PubMed: 31812082
DOI: 10.1016/j.clinph.2019.11.003 -
Neuropsychology Review Dec 2019Rett syndrome is the second most common cause of intellectual disability in females worldwide. The severity of many individuals' impairment limits the effectiveness of...
Rett syndrome is the second most common cause of intellectual disability in females worldwide. The severity of many individuals' impairment limits the effectiveness of traditional assessment. However, clinician and parent reports of adaptive functioning may provide insight into these patients' abilities. This review aims to synthesize the current literature assessing adaptive functioning in Rett syndrome and evaluate existing measurement tools in this population. A search was conducted on PubMed using the search term "Rett syndrome." Studies that quantitatively assessed adaptive functioning outcomes in Rett syndrome with published and normed questionnaire measures were included. Twenty-three studies met inclusion criteria. Overall results indicate that the population of people with Rett syndrome is highly impaired, both in overall adaptive functioning as well as in specific subdomains (e.g., mobility, activities of daily living). Atypical Rett syndrome groups performed better on measures of adaptive functioning relative to patients with classic Rett syndrome. Our findings identified measurement weaknesses, as many of the studies found floor effects and therefore were unable to capture meaningful variability in outcomes. Individuals with Rett syndrome are highly reliant on caregivers due to disrupted adaptive functioning abilities. Optimizing measurement of adaptive skills in Rett syndrome will facilitate the quantification of meaningful change in skills and the identification of efficacious interventions aimed at improving outcomes and quality of life.
Topics: Activities of Daily Living; Adaptation, Psychological; Caregivers; Communication; Health Personnel; Humans; Psychological Tests; Rett Syndrome; Socialization
PubMed: 31748842
DOI: 10.1007/s11065-019-09420-9 -
Journal of Psychiatry & Neuroscience :... May 2020Rett syndrome (RTT), a debilitating neuropsychiatric disorder that begins in early childhood, is characterized by impairments in the autonomic nervous system that can...
BACKGROUND
Rett syndrome (RTT), a debilitating neuropsychiatric disorder that begins in early childhood, is characterized by impairments in the autonomic nervous system that can lead to sudden unexpected death. This study explores the mechanisms of autonomic dysfunction to identify potential risk factors for sudden death in patients with RTT.
METHODS
Following the Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria, we undertook comprehensive systematic reviews using the PubMed, Scopus, Cochrane, PsycINFO, Embase and Web of Science databases.
RESULTS
We identified and critically appraised 39 articles for autonomic dysfunction and 5 for sudden death that satisfied the eligibility criteria. Following thematic analysis, we identified 7 themes: breathing irregularities, abnormal spontaneous brainstem activations, heart rate variability metrics, QTc changes, vagal imbalance, fluctuation in peptides and serotonergic neurotransmission. We grouped these 7 themes into 3 final themes: (A) brainstem modulation of breathing, (B) electrical instability of the cardiovascular system and (C) neurochemical changes contributing to autonomic decline. We described key evidence relating to each theme and identified important areas that could improve the clinical management of patients with RTT.
LIMITATIONS
The heterogeneity of the methods used to assess autonomic function increased the difficulty of making inferences from the different studies.
CONCLUSION
This study identified the important mediators of autonomic dysfunction and sudden death in patients with RTT. We proposed brainstem mechanisms and emphasized risk factors that increase brainstem vulnerability. We discussed clinical management to reduce sudden death and future directions for this vulnerable population.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Brain Stem; Death, Sudden; Humans; Rett Syndrome; Risk Factors
PubMed: 31702122
DOI: 10.1503/jpn.190033 -
Developmental Neurorehabilitation Nov 2020In recent years, much attention has been paid to motor impairment of persons with Rett Syndrome (RTT), with increasing literature aimed to describe gross motor...
In recent years, much attention has been paid to motor impairment of persons with Rett Syndrome (RTT), with increasing literature aimed to describe gross motor functioning and musculoskeletal disorders of the RTT population. The aim of this systematic review is to describe clinical evaluation tools used in the last decade to assess motor functioning and musculoskeletal abnormalities of patients with RTT. Thirty-four studies were reviewed and 20 tools were presented. Results showed that only two tools were used to measure functional change after rehabilitative or therapeutic interventions. This review underlies the lack of adequate evaluation tools to assess musculoskeletal abnormalities and deformities in RTT population. The absence of these assessments could be due to a statistical difficulty as it is challenging to build an evaluation tool that can score the entities of the abnormalities related to the amount of disability they cause.
Topics: Child; Disability Evaluation; Exercise; Humans; Movement Disorders; Musculoskeletal Diseases; Rett Syndrome
PubMed: 31668104
DOI: 10.1080/17518423.2019.1680761