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European Journal of Medical Research Mar 2024Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of... (Review)
Review
BACKGROUND
Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients.
METHODS
The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here.
RESULTS
The mean age at symptom onset was generally 16-18 months for late-infantile MLD and 6-10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures.
CONCLUSIONS
Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.
Topics: Adult; Humans; Leukodystrophy, Metachromatic; Quality of Life; Cost of Illness
PubMed: 38494502
DOI: 10.1186/s40001-024-01771-1 -
Frontiers in Neurology 2024To review the clinical characteristics and effect of treatment in patients with spinal muscular atrophy (SMA) and three copies of the gene.
The impact of three gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review.
OBJECTIVE
To review the clinical characteristics and effect of treatment in patients with spinal muscular atrophy (SMA) and three copies of the gene.
METHODS
We conducted a literature search in October 2022 to identify English-language clinical research on SMA that included copy number according to PRISMA guidelines.
RESULTS
Our search identified 44 studies examining the impact of three copies on clinical characteristics (21 on phenotype, 13 on natural history, and 15 on functional status and other signs/symptoms). In children with type I SMA or presymptomatic infants with an deletion, three copies was associated with later symptom onset, slower decline in motor function and longer survival compared with two copies. In patients with SMA type II or III, three copies is associated with earlier symptom onset, loss of ambulation, and ventilator dependence compared with four copies. Eleven studies examined treatment effects with nusinersen (nine studies), onasemnogene abeparvovec (one study), and a range of treatments (one study) in patients with three copies. In presymptomatic infants, early treatment delayed the onset of symptoms and maintained motor function in those with three copies. The impact of copy number on treatment response in symptomatic patients is still unclear.
CONCLUSION
copy number is strongly correlated with SMA phenotype in patients with deletion, while no correlation was found in patients with an mutation. Patients with three copies show a highly variable clinical phenotype. Early initiation of treatment is highly effective in presymptomatic patients with three copies.
PubMed: 38487326
DOI: 10.3389/fneur.2024.1308296 -
American Journal of Obstetrics and... Mar 2024This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes. (Review)
Review
OBJECTIVE
This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes.
DATA SOURCES
MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023.
STUDY ELIGIBILITY CRITERIA
Studies of women who received treatment with metformin at any stage of pregnancy for any indication with neurodevelopmental data available for their offspring were included. Studies without a control group were excluded. Randomized controlled trials, case-control, cohort, and cross-sectional studies were included in the review.
METHODS
Studies were screened for inclusion and data were extracted independently by 2 reviewers. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale for nonrandomized studies, and the Risk of Bias 2 tool for randomized trials.
RESULTS
A total of 7 studies met the inclusion criteria, including a combined cohort of 14,042 children with 7641 children who were exposed and followed for up to 14 years of age. Metformin use during pregnancy was not associated with neurodevelopmental delay in infancy (relative risk, 1.09; 95% confidence interval, 0.54-2.17; 3 studies; 9668 children) or at ages 3 to 5 years (relative risk, 0.90; 95% confidence interval, 0.56-1.45; 2 studies; 6118 children). When compared with unexposed peers, metformin use during pregnancy was not associated with altered motor scores (mean difference, 0.30; 95% confidence interval, -1.15 to 1.74; 3 studies; 714 children) or cognitive scores (mean difference, -0.45; 95% confidence interval, -1.45 to 0.55; 4 studies; 734 children). Studies that were included were of high quality and deemed to be at low risk of bias.
CONCLUSION
In utero exposure to metformin does not seem to be associated with adverse neurodevelopmental outcomes in children up to the age of 14 years. These findings provide reassurance to clinicians and pregnant women considering metformin use during pregnancy.
PubMed: 38460832
DOI: 10.1016/j.ajog.2024.02.316 -
Emergency Radiology Apr 2024Trauma is a significant cause of mortality and morbidity. It is crucial to diagnose trauma patients quickly to provide effective treatment interventions in such... (Meta-Analysis)
Meta-Analysis Review
Trauma is a significant cause of mortality and morbidity. It is crucial to diagnose trauma patients quickly to provide effective treatment interventions in such conditions. Whole-body computed tomography (WBCT)/pan-scan is an imaging technique that enables a faster and more efficient diagnosis for polytrauma patients. The purpose of this systematic review and meta-analysis is to evaluate the efficacy of WBCT in diagnosing injuries in polytrauma patients. We will also assess its impact on the mortality rate and length of hospital stay among trauma centers between patients who underwent WBCT and those who did not (non-WBCT). Twenty-seven studies meeting our inclusion criteria were selected among PubMed, Scopus, Web of Science, and Google Scholar. The criteria were centered on the significance of WBCT/pan-scan application in trauma patients. Stata version 15 was used to perform statistical analysis on the data. The authors have also used I statistics to evaluate heterogeneity. Egger and Begg's tests were performed to rule out any publication bias. Total of twenty-seven studies including 68,838 trauma patients with a mean age of 45.0 ± 24.7 years were selected. Motor vehicle collisions were the most common cause of blunt injuries (80.0%). Head, neck, and face injuries were diagnosed in 44% (95% CI, 0.28-0.60; I = 99.8%), 6% (95% CI, 0.02-0.09; I = 97.2%), and 9% (95% CI, 0.05-0.13; I = 97.1%), respectively. Chest injuries were diagnosed by WBCT in 39% (95% CI, 0.28-0.51; I = 99.8%), abdominal injuries in 23% (95% CI, 0.03-0.43; I = 99.9%) of cases, spinal injuries 19% (95% CI, 0.11-0.27; I = 99.4%), extremity injuries 33% (95% CI, 0.23-0.43; I = 99.2%), and pelvic injuries 11% (95% CI, 0.04-0.18; I = 97.4%). A mortality odd ratio of 0.94 (95% CI, 0.83-1.06; I = 40.1%) was calculated while comparing WBCT and non-WBCT groups. This systematic review and meta-analysis provide insight into the possible safety, efficacy, and efficiency of WBCT/pan-scan as a diagnostic tool for trauma patients with serious injuries, regardless of their hemodynamic status. In patients with serious injuries from trauma, whether or not there are indicators of hemodynamic instability, our recommended approach is to, wherever possible, perform a WBCT without stopping the hemostatic resuscitation. By using this technology, the optimal surgical strategy for these patients can be decided upon without causing any delays in their final care or greatly raising their radiation dose.
Topics: Humans; Young Adult; Adult; Middle Aged; Aged; Multiple Trauma; Tomography, X-Ray Computed; Thoracic Injuries; Trauma Centers; Wounds, Nonpenetrating; Whole Body Imaging; Retrospective Studies
PubMed: 38396199
DOI: 10.1007/s10140-024-02213-5 -
Diagnostics (Basel, Switzerland) Nov 2023Preterm infants are more likely to demonstrate developmental delays than fullterm infants. Postural measurement tools may be effective in measuring the center of... (Review)
Review
Preterm infants are more likely to demonstrate developmental delays than fullterm infants. Postural measurement tools may be effective in measuring the center of pressure (COP) and asymmetry, as well as predicting future motor impairment. The objective of this systematic review was to evaluate existing evidence regarding use of pressure mats or force plates for measuring COP and asymmetry in preterm infants, to determine how measures differ between preterm and fullterm infants and if these tools appropriately predict future motor impairment. The consulted databases included PubMed, Embase, Scopus, and CINAHL. The quality of the literature and the risk of bias were assessed utilizing the ROB2: revised Cochrane risk-of bias tool. Nine manuscripts met the criteria for review. The postural control tools included were FSA UltraThin seat mat, Conformat Pressure-Sensitive mat, Play and Neuro-Developmental Assessment, and standard force plates. Studies demonstrated that all tools were capable of COP assessment in preterm infants and support the association between the observation of reduced postural complexity prior to the observation of midline head control as an indicator of future motor delay. Postural measurement tools provide quick and objective measures of postural control and asymmetry. Based on the degree of impairment, these tools may provide an alternative to standardized assessments that may be taxing to the preterm infant, inaccessible to therapists, or not sensitive enough to capture motor delays.
PubMed: 37998609
DOI: 10.3390/diagnostics13223473 -
Pediatric Research Feb 2024This meta-analysis aimed to identify the near- and long-term neurodevelopmental prognoses of preterm or low birth weight (LBW) infants with different severities of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to identify the near- and long-term neurodevelopmental prognoses of preterm or low birth weight (LBW) infants with different severities of intraventricular hemorrhage (IVH).
METHODS
Four databases were searched for observational studies that were qualified using the Newcastle-Ottawa Scale.
RESULTS
37 studies involving 32,370 children were included. Compared to children without IVH, children with mild IVH had higher incidences of neurodevelopmental impairment (NDI), cerebral palsy (CP), motor/cognitive delay, hearing impairment and visual impairment, as well as lower scores of the mental development index (MDI) and psychomotor development (PDI). Moreover, compared to mild IVH, severe IVH increased susceptibilities of children to NDI, motor delay, CP, hearing impairment and visual impairment, with worse performances in MDI, PDI, motor score and IQ. Mild IVH was not associated with seizures or epilepsy.
CONCLUSIONS
Adverse neurodevelopmental outcomes positively associated with the occurrence and severity of IVH in preterm or LBW infants, providing evidence for counseling and further decisions regarding early therapeutic interventions.
IMPACT
Adverse neurodevelopmental outcomes later in life were closely associated with the occurrence and severity of IVH in preterm or LBW infants. Our results highlight the importance to make prediction of the neurodevelopmental outcomes of children born preterm or LBW with a history of IVH, which will guide affected parents when their children need clinical interventions to reach the full potential. We emphasize the importance of identifying specific developmental delays that may exist in children with IVH, providing detailed information for the development of comprehensive intervention measures.
Topics: Infant, Newborn; Infant; Child; Humans; Infant, Premature; Infant, Premature, Diseases; Infant, Low Birth Weight; Cerebral Hemorrhage; Cerebral Palsy; Hearing Loss; Vision Disorders
PubMed: 37935882
DOI: 10.1038/s41390-023-02877-8 -
Children (Basel, Switzerland) Oct 2023This study examines the last 10 years of medical literature on the benefits of cochlear implantation in children who are deaf or hard of hearing (DHH) with additional... (Review)
Review
This study examines the last 10 years of medical literature on the benefits of cochlear implantation in children who are deaf or hard of hearing (DHH) with additional disabilities. The most recent literature concerning cochlear implants (CIs) in DHH children with additional disabilities was systematically explored through PubMed, Embase, Scopus, PsycINFO, and Web of Science from January 2012 to July 2023. Our two-stage search strategy selected a total of 61 articles concerning CI implantation in children with several forms of additional disabilities: autism spectrum disorder, cerebral palsy, visual impairment, motor disorders, developmental delay, genetic syndromes, and intellectual disability. Overall, many children with additional disabilities benefit from CIs by acquiring greater environmental sound awareness. This, in turn, improves non-verbal communication and adaptive skills, with greater possibilities to relate to others and to be connected with the environment. Instead, despite some improvement, expressive language tends to develop more slowly and to a lesser extent compared to children affected by hearing loss only. Further studies are needed to better appreciate the specificities of each single disability and to personalize interventions, not restricting the analysis to auditory and language skills, but rather applying or developing cross-culturally validated instruments able to reliably assess the developmental trajectory and the quality of life of DHH children with additional disabilities before and after CI.
PubMed: 37892316
DOI: 10.3390/children10101653 -
Neuropsychiatric Disease and Treatment 2023The gene encodes the thyroid hormone (TH) transporter MCT8. Pathogenic variants result in a reduced TH uptake into the CNS despite high serum T3 concentrations....
INTRODUCTION
The gene encodes the thyroid hormone (TH) transporter MCT8. Pathogenic variants result in a reduced TH uptake into the CNS despite high serum T3 concentrations. Patients suffer from severe neurodevelopmental delay and require multidisciplinary care. Since a first compassionate use study in 2008, the development of therapies has recently gained momentum. Treatment strategies range from symptom-based approaches, supplementation with TH or TH-analogs, to gene therapy. All these studies have mainly used surrogate endpoints and clinical outcomes. However, the EMA and FDA strongly encourage researchers to involve patients and their advocacy groups in the design of clinical trials. This should strengthen the patients' perspective and identify clinical endpoints that are clinically relevant to their daily life.
METHODS
We involved patient families to define patient-relevant outcomes for MCT8 deficiency. In close collaboration with patient families, we designed a questionnaire asking for their five most preferred therapeutic goals, which, if achieved at least, make a difference in their lives. In addition, we performed a systematic review according to Cochrane recommendations of the published treatment trials.
RESULTS
We obtained results from 15 families with completed questionnaires from 14 mothers and 8 fathers. Improvement in development, especially in gross motor skills, was most important to the parents. 59% wished for head control and 50% for sitting ability. Another 36% wished for weight gain, 32% for improvement of expressive language skills, and 18% for a reduction of dystonia/spasticity, less dysphagia, and reflux. Paraclinical aspects were least important (5-9%). In a treatment trial (n=46) and compassionate use cases (n=83), the results were mainly inconclusive, partly due to a lack of predefined patient-centered clinical endpoints.
DISCUSSION
We recommend that future trials should define a relevant improvement in "development" and/or other patient-relevant outcomes compared to natural history as treatment goals.
PubMed: 37881807
DOI: 10.2147/NDT.S379703 -
Cureus Sep 2023The goal of the present systematic review was to investigate the occurrence patterns of intermittent hypoxemia in newborns throughout the early postnatal period as well... (Review)
Review
The goal of the present systematic review was to investigate the occurrence patterns of intermittent hypoxemia in newborns throughout the early postnatal period as well as the link between neonatal intermittent hypoxemia exposure and harmful consequences such as neonatal morbidity and death. We collected data from 2014 to 2023 using several abstracting, referencing, and indexing database libraries in the field of medical sciences. A total of 715 papers were evaluated by both authors, and only seven articles met the specified review criteria after a thorough analysis. In preterm neonates with intermittent hypoxia (IH), severe morbidities such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), motor impairment, and cognitive delay were found. Only one study that extended to 18 months noted mortality. The length and occurrence of intermittent hypoxemia and the stage of premature neonates at the time of delivery are all closely associated with these morbidities. Therefore, it becomes important to continuously measure the patterns of occurrence of intermittent hypoxemia during early postnatal life to avoid its long-term morbidity and mortality impact.
PubMed: 37868466
DOI: 10.7759/cureus.45561 -
Neurorehabilitation and Neural Repair Oct 2023We aimed to identify key aspects of the learning dynamics of proprioception training including: 1) specificity to the training type, 2) acquisition of proprioceptive... (Review)
Review
OBJECTIVE
We aimed to identify key aspects of the learning dynamics of proprioception training including: 1) specificity to the training type, 2) acquisition of proprioceptive skills, 3) retention of learning effects, and 4) transfer to different proprioceptive skills.
METHODS
We performed a systematic literature search using the database (MEDLINE, EMBASE, Cochrane Library, and PEDro). The inclusion criteria required adult participants who underwent any training program that could enhance proprioceptive function, and at least 1 quantitative assessment of proprioception before and after the intervention. We analyzed within-group changes to quantify the effectiveness of an intervention.
RESULTS
In total, 106 studies with 343 participant-outcome groups were included. Proprioception-specific training resulted in large effect sizes with a mean improvement of 23.4 to 42.6%, nonspecific training resulted in medium effect sizes with 12.3 to 22% improvement, and no training resulted in small effect sizes with 5.0 to 8.9% improvement. Single-session training exhibited significant proprioceptive improvement immediately (10 studies). For training interventions with a midway evaluation (4 studies), trained groups improved by approximately 70% of their final value at the midway point. Proprioceptive improvements were largely maintained at a delayed follow-up of at least 1 week (12 studies). Finally, improvements in 1 assessment were significantly correlated with improvements in another assessment (10 studies).
CONCLUSIONS
Proprioceptive learning appears to exhibit several features similar to motor learning, including specificity to the training type, 2 time constant learning curves, good retention, and improvements that are correlated between different assessments, suggesting a possible, common mechanism for the transfer of training.
Topics: Adult; Humans; Proprioception; Learning
PubMed: 37864458
DOI: 10.1177/15459683231207354