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European Spine Journal : Official... Jun 2024Surgical correction of neuromuscular scoliosis is often a challenging and extensive procedure. Due to this complexity and the high disease burden that these patients... (Review)
Review
PURPOSE
Surgical correction of neuromuscular scoliosis is often a challenging and extensive procedure. Due to this complexity and the high disease burden that these patients carry, per and post-operative complications are not uncommon. The purpose of this study was to systematically review and describe the pooled rates of postoperative complications and analyze risk factors for complications in neuromuscular scoliosis surgery described in the literature in the last ten years.
METHODS
A systematic review of the English literature across multiple databases was conducted using search criteria (neuromuscular scoliosis AND complications) and using PRISMA guidelines (Jan 2012-July 2022). Studies with less than 30 patients and follow-up of < 2 years were excluded. Data extraction and meta-analysis were performed using random mode effect. Statistical analysis was conducted using OpenMeta software. Meta-regression analysis was used to detect risk factors (surgical approach, intraoperative time, intraoperative blood loss, preoperative Cobb angle and patient diagnosis) associated with each complication group. Confidence interval (CI) was set at 95%.
RESULTS
Twenty-two studies met the inclusion criteria involving 2155 patients. The level of evidence among studies were III (9) and IV (13). The most common primary diagnosis was cerebral palsy (43%) followed by Duchenne muscle dystrophy (20%), myelomeningocele (7.4%), spinal muscle atrophy (7.1%), Rett syndrome (< 2%) and combined other pathologies (20.2%). The pooled incidence rate of wound complications was the highest, amongst all complications, at 13.3% (CI 10.838 to 16.861); closely followed by respiratory complications (11.8%;CI 5.7 to 19.7). Implant failure occurred in 7.1% cases (CI 6.418 to 11.465), gastrointestinal complications was 5.2%; CI 2.4 to 8), pseudarthrosis in (4.6%;CI 2.2 to 6.9) and neurological deficit in 2.9% (CI 1.989 to 6.086). The pooled rate of revision surgery was (9.6%; CI 6.2 to 12.9). Heterogeneity was assessed using I test which results were moderately heterogeneous. Meta-regression analysis revealed that the diagnosis of myelomeningocele or Duchenne muscle dystrophy or spinal muscle atrophy were strongly associated with wound and respiratory complications (p = 0.007 and p = 0.005, respectively).
CONCLUSION
Wound-related (13.3%) and respiratory complications (11.8%) remain the most common complications among studies after corrective surgery for neuromuscular scoliosis. Both are significantly associated with Duchenne muscle dystrophy, spinal muscle atrophy and myelomeningocele.
PubMed: 38869648
DOI: 10.1007/s00586-024-08338-y -
BMC Pediatrics Mar 2024Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett syndrome, there is a dire need for effective interventions.
OBJECTIVE
To evaluate the safety and efficacy of trofinetide in Randomized Controlled Trials (RCTs) that report on Rett syndrome patients.
METHODS
We identified 109 articles from four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL). After removing the duplicates, we narrowed them down to 59 articles for further assessment. We included RCTs that evaluated the efficacy and safety of trofinetide in patients with Rett syndrome. Three studies were eligible for inclusion. Two independent reviewers evaluated the identified studies' titles, abstracts, and full texts, extracting pertinent data. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) 2.0 tool. We then conducted a meta-analysis using the fixed effects model in the case of insignificant heterogeneity; otherwise, we used the random effects model. Based on the nature of the outcome, we analyzed the mean difference or the odds ratio. Analysis was conducted using RevMan version 5.3.
RESULTS
Among the analyzed outcomes in 181 patients in the trofinetide group and 134 patients in the placebo group, significant improvement in Rett Syndrome Behavior Questionnaire (RSBQ) scores was observed at 200 mg dosage (overall mean difference: -3.53, p = 0.001). Clinical Global Impression-Improvement (CGI-I) scores improved considerably at 200 mg dosage (overall mean difference: -0.34, p < 0.0001). No substantial changes were observed in Motor Behavioral Assessment (MBA) or Top 3 Caregiver Concerns. We evaluated Treatment Emergent Adverse Events (TEAEs) across the various dosages and noted significant associations with diarrhea (200 mg), vomiting (200 mg), and irritability (200 mg). However, we did not find a significant association between any of the dosages and the incidence of decreased appetite.
CONCLUSION
Trofinetide demonstrated potential in improving RSBQ and CGI-I scores at 200 mg dosage. Although no substantial changes were found in MBA and top 3 caregiver concerns. Adverse events were linked to specific dosages.
Topics: Female; Humans; Rett Syndrome; Randomized Controlled Trials as Topic; Glutamates; Diarrhea
PubMed: 38521908
DOI: 10.1186/s12887-024-04526-3 -
Frontiers in Neuroscience 2024Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent...
Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.
INTRODUCTION
Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT).
METHODS
We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design.
RESULTS
Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with (phylum Firmicutes) and positively correlated with sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition.
DISCUSSION
Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior.
SYSTEMATIC REVIEW REGISTRATION
https://clinicaltrials.gov/, CRD42020158734.
PubMed: 38516317
DOI: 10.3389/fnins.2024.1341656 -
International Journal of Molecular... May 2023This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies,... (Review)
Review
This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search six databases during the last decade, followed by a thematic analysis to identify the emerging themes. Thematic analysis across the different disorders revealed four themes: (I) Therapeutic time window of gene therapy; (II) Administration and dosing strategies for gene therapy; (III) Methods of gene therapeutics and (IV) Future areas of clinical interest. Our synthesis of information has further enriched the current clinical evidence base and can assist in optimising gene therapy and gene editing studies in individuals with RTT, but it would also benefit when applied to other disorders. The findings suggest that gene therapies have better outcomes when the brain is not the primary target. Across different disorders, early intervention appears to be more critical, and targeting the pre-symptomatic stage might prevent symptom pathology. Intervention at later stages of disease progression may benefit by helping to clinically stabilise patients and preventing disease-related symptoms from worsening. If gene therapy or editing has the desired outcome, older patients would need concerted rehabilitation efforts to reverse their impairments. The timing of intervention and the administration route would be critical parameters for successful outcomes of gene therapy/editing trials in individuals with RTT. Current approaches also need to overcome the challenges of MeCP2 dosing, genotoxicity, transduction efficiencies and biodistribution.
Topics: Humans; Rett Syndrome; Gene Editing; Tissue Distribution; Methyl-CpG-Binding Protein 2; Brain; Genetic Therapy
PubMed: 37240368
DOI: 10.3390/ijms24109023 -
Neuroscience and Biobehavioral Reviews Jun 2023We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and... (Review)
Review
The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications.
We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.
Topics: Humans; Child; Adolescent; Psychopharmacology; Randomized Controlled Trials as Topic; Attention Deficit Disorder with Hyperactivity; Prader-Willi Syndrome; Clinical Trials, Phase II as Topic
PubMed: 37001575
DOI: 10.1016/j.neubiorev.2023.105149 -
Movement Disorders Clinical Practice Jan 2023With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we... (Review)
Review
BACKGROUND
With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms.
METHODS
A systematic literature review was conducted in PubMed and Embase on June 15, 2021. Search terms for parkinsonism and genetic neurodevelopmental disorders, using generic terms and the Human Phenotype Ontology, were combined. Study characteristics and descriptive data were extracted from the articles using a modified version of the Cochrane Consumers and Communication Review Group's data extraction template. The protocol was registered in PROSPERO (CRD42020191035).
RESULTS
The literature search yielded 208 reports for data-extraction, describing 69 genetic disorders in 422 patients. The five most reported from most to least frequent were: 22q11.2 deletion syndrome, beta-propeller protein-associated neurodegeneration, Down syndrome, cerebrotendinous xanthomatosis, and Rett syndrome. Notable findings were an almost equal male to female ratio, an early median age of motor onset (26 years old) and rigidity being more common than rest tremor. Results of dopaminergic imaging and response to antiparkinsonian medication often supported the neurodegenerative nature of parkinsonism. Moreover, neuropathology results showed neuronal loss in the majority of cases. Proposed disease mechanisms included aberrant mitochondrial function and disruptions in neurotransmitter metabolism, endosomal trafficking, and the autophagic-lysosomal and ubiquitin-proteasome system.
CONCLUSION
Parkinsonism has been reported in many GNDs. Findings from this study may provide clues for further research and improve management of patients with GNDs and/or parkinsonism.
PubMed: 36699000
DOI: 10.1002/mdc3.13577 -
Systematic Reviews Jan 2023Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Diagnostic criteria for typical Rett syndrome require a period of regression, followed by recovery or stabilization, and fulfillment of all four main criteria (loss of purposeful hand skills, loss of spoken language, gait abnormalities, and stereotypic hand movements). Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex.
METHODS
We conducted a search of PubMed, Embase, Web of Science, Cochrane Library, LILACS, and LIVIVO to retrieve studies published in English between Jan. 1, 2000, and June 30, 2021. Pooled prevalence with a 95% confidence interval (CI) was estimated using a random-effects meta-analysis based on a generalized linear mixed model with a logit link.
RESULTS
Ten eligible studies were identified (all in females), with a combined sample size of 9.57 million women and 673 Rett syndrome cases. The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p < 0.001). Despite greatly variable precision of estimation, all estimates were compatible with a prevalence range of approximately 5 to 10 cases per 100,000 females based on their respective 95% CIs.
CONCLUSION
These findings may facilitate planning of therapeutic trials in this indication in terms of target sample size and accrual times.
Topics: Humans; Female; Rett Syndrome; Methyl-CpG-Binding Protein 2; Prevalence; Mutation
PubMed: 36642718
DOI: 10.1186/s13643-023-02169-6 -
Frontiers in Neurology 2022Rett Syndrome (RTT, OMIM 312750), a unique rare neurodevelopmental disorder, mostly affects females and causes severe multi-disabilities including poor sleep. This...
UNLABELLED
Rett Syndrome (RTT, OMIM 312750), a unique rare neurodevelopmental disorder, mostly affects females and causes severe multi-disabilities including poor sleep. This meta-analysis systematically reviewed the polysomnographic (PSG) data of individuals with RTT on both sleep macrostructure and sleep respiratory indexes and compared them to literature normative values. Studies were collected from PubMed, Web of Science, PsycINFO, Ebsco, Scopus, and Cochrane Library till 26 April 2022. Across 13 included studies, the 134 selected RTT cases were mostly females being ( = 41) and ( = 4) positive. They were further stratified by gene, age, and clinical features. Findings of comparison with literature normative values suggested shorter total sleep time (TST) and sleep onset latency (SOL), twice as long wake after sleep onset (WASO) with lower sleep efficiency (SEI) in RTT, as well as increased non-rapid eye movement stage 3 (stage N3) and decreased rapid eye movement sleep. Based on limited data per stratifications, we found in RTT cases <5 years old lower stage N3, and in RTT cases >5 years old less WASO and more WASO in the epileptic strata. However, meta-results generated from studies designed with comparison groups only showed lower stage N1 in RTT than in healthy comparison, together with similar SEI and stage N3 to primary snoring subjects. For sleep respiratory indexes, severe disordered sleep breathing was confirmed across roughly all RTT strata. We are the first study to meta-analyze PSG data of subjects with RTT, illustrating shorter TST and aberrant sleep staging in RTT that may vary with age or the presence of epilepsy. Severe nocturnal hypoxemia with apneic events was also demonstrated. More studies are needed to explore and elucidate the pathophysiological mechanisms of these sleep findings in the future.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198099, identifier: CRD 42020198099.
PubMed: 36203990
DOI: 10.3389/fneur.2022.963626 -
Developmental Medicine and Child... Feb 2023To synthesize existing evidence on the effectiveness of speech-language teleinterventions delivered via videoconferencing to users of augmentative and alternative...
AIM
To synthesize existing evidence on the effectiveness of speech-language teleinterventions delivered via videoconferencing to users of augmentative and alternative communication (AAC) devices.
METHOD
A systematic literature search was conducted in 10 electronic databases, from inception until August 2021. Included were speech-language teleinterventions delivered by researchers and/or clinicians via videoconferencing to users of AAC devices, without restrictions on chronological age and clinical diagnosis. The quality of the studies included in the review was appraised using the Downs and Black checklist and the Single-Case Experimental Design Scale; risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies - of Interventions and the single-case design risk of bias tools.
RESULTS
Six teleinterventions including 25 participants with a variety of conditions, such as Down syndrome, autism, Rett syndrome, and amyotrophic lateral sclerosis met the inclusion criteria. Five studies used a single-case experimental design and one was a cohort study. Teleinterventions included active consultation (n = 2), functional communication training (n = 2), brain-computer interface (n = 1), and both teleintervention and in-person intervention (n = 1). All teleinterventions reported an increase in participants' independent use of AAC devices during the training sessions compared to baseline, as well as an overall high satisfaction and treatment acceptability.
INTERPRETATION
Speech-language teleinterventions for users of AAC devices show great potential for a successful method of service delivery. Future telehealth studies with larger sample sizes and more robust methodology are strongly encouraged to allow the generalization of results across different populations.
WHAT THIS PAPER ADDS
Individuals can learn to use augmentative and alternative communication (AAC) devices independently during tele-AAC interventions. Service providers and recipients reported an overall high satisfaction and acceptability for AAC services delivered via teleinterventions. Speech-language teleinterventions may be an effective method of providing AAC intervention services.
Topics: Humans; Cohort Studies; Communication Disorders; Autistic Disorder; Language Therapy; Communication
PubMed: 36047007
DOI: 10.1111/dmcn.15387 -
Brain Sciences Jul 2022Eye movement abnormalities in association with cognitive and emotional deficits have been described in neurological, neurodevelopmental, and psychiatric disorders.... (Review)
Review
Eye movement abnormalities in association with cognitive and emotional deficits have been described in neurological, neurodevelopmental, and psychiatric disorders. Eye-Tracking (ET) techniques could therefore enhance cognitive interventions by contingently providing feedback to patients. Since no consensus has been reached thus far on this approach, this study aimed at systematically reviewing the current evidence. This review was performed and reported according to PRISMA guidelines. Records were searched for in PubMed, Web of Science, and Scopus (1990-2021) through the following string: ('Eye Tracking' OR 'Eye-Tracking' OR 'Oculomotor') AND ('Neuropsychol*' OR 'Cognitive') AND ('Rehabilitation' OR 'Training' OR 'Stimulation'). Study outcomes were thematically classified and qualitatively synthesized. A structured quality assessment was performed. A total of 24 articles were included, addressing neurodevelopmental (preterm infants and children with autism spectrum disorder, Rett syndrome, or ADHD; = 14), psychiatric (mood and anxiety disorders or alcohol dependence; = 7), and neurological conditions (stroke; = 3). Overall, ET gaze-contingent training proved to be effective in improving cognitive and emotional alterations. However, population heterogeneity limits the generalizability of results. ET gaze-contingent protocols allow researchers to directly and dynamically train attentional functions; together with the recruitment of implicit, "bottom-up" strategies, these protocols are promising and possibly integrable with traditional cognitive approaches.
PubMed: 35884737
DOI: 10.3390/brainsci12070931