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Cureus Mar 2023Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This... (Review)
Review
Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This disease is difficult to diagnose since its symptoms are similar to those of the aging process. Those with PD have impaired motor control and function, dyskinesia, and tremors. To treat PD, drugs that enhance the amount of dopamine given to the brain are administered to alleviate symptoms. This inquiry examines the prescription of rotigotine to achieve this objective. The primary objective of this review is to examine the usage of rotigotine in both the late and early stages of PD. The statistical model utilized in the review found that there was not a significant difference in the dosage of rotigotine prescribed to late and early-stage PD patients, however, there were some confounding variables that may have skewed this result; therefore, further research is necessary to validate or nullify this hypothesis.
PubMed: 37069881
DOI: 10.7759/cureus.36211 -
Genes Feb 2023Defect of , the human mitochondrial tRNA-modifying enzyme, can lead to Combined Oxidative Phosphorylation Deficiency 23 (COXPD23). Up to now, about 20 different variants...
Defect of , the human mitochondrial tRNA-modifying enzyme, can lead to Combined Oxidative Phosphorylation Deficiency 23 (COXPD23). Up to now, about 20 different variants of the gene have been reported; however, genotype-phenotype analysis has rarely been described. Here, we reported a 9-year-old boy with COXPD23 who presented with hyperlactatemia, hypertrophic cardiomyopathy, seizures, feeding difficulties, intellectual disability and motor developmental delay, and abnormal visual development. Biallelic pathogenic variants of the gene were identified in this boy, one novel variant c.1102dupC (p. Arg368Profs*22) inherited from the mother and the other known variant c.689A>C (p. Gln230Pro) inherited from father. We curated 18 COXPD23 patients with variants to investigate the genotype-phenotype correlation. We found that hyperlactatemia and cardiomyopathy were critical clinical features in COXPD23 and the average onset age was 1.7 years (3 months of age for the homozygote). Clinical classification of COXPD23 for the two types, severe and mild, was well described in this study. We observed arrhythmia and congestive heart failure frequently in the severe type with early childhood mortality, while developmental delay was mainly observed in the mild type. The proportion of homozygous variants (71.4%) significantly differed from that of compound heterozygous variants (18.1%) in the severe type. Compared with the variants in gnomAD, the proportion of LOFVs in was higher in COXPD23 patients (48.6% versus 8.9%, < 0.0001 ****), and 31% of them were frameshift variants, showing the LOF mechanism of . Additionally, the variants in patients were significantly enriched in the TrmE-type G domain, indicating that the G domain was crucial for protein function. The TrmE-type G domain contained several significant motifs involved in the binding of guanine nucleotides and Mg, the hydrolysis of GTP, and the regulation of the functional status of GTPases. In conclusion, we reported a mild COXPD23 case with typical -related symptoms, including seizures and abnormal visual development seldom observed previously. Our study provides novel insight into understanding the clinical diagnosis and genetic counseling of patients with COXPD23 by exploring the genetic pathogenesis and genotype-phenotype correlation of COXPD23.
Topics: Child; Child, Preschool; Humans; Infant; Male; GTP-Binding Proteins; Hyperlactatemia; Mitochondrial Diseases; Seizures
PubMed: 36980825
DOI: 10.3390/genes14030552 -
Children (Basel, Switzerland) Mar 2023Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein... (Review)
Review
BACKGROUND
Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects).
PATIENTS AND METHODS
We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected.
RESULTS
497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed.
CONCLUSIONS
Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.
PubMed: 36980111
DOI: 10.3390/children10030553 -
International Journal of Molecular... Feb 2023The use of neuraxial procedures, such as spinal and epidural anaesthesia, has been linked to some possible complications. In addition, spinal cord injuries due to... (Review)
Review
The use of neuraxial procedures, such as spinal and epidural anaesthesia, has been linked to some possible complications. In addition, spinal cord injuries due to anaesthetic practice (Anaes-SCI) are rare events but remain a significant concern for many patients undergoing surgery. This systematic review aimed to identify high-risk patients summarise the causes, consequences, and management/recommendations of SCI due to neuraxial techniques in anaesthesia. A comprehensive search of the literature was conducted in accordance with Cochrane recommendations, and inclusion criteria were applied to identify relevant studies. From the 384 studies initially screened, 31 were critically appraised, and the data were extracted and analysed. The results of this review suggest that the main risk factors reported were extremes of age, obesity, and diabetes. Anaes-SCI was reported as a consequence of hematoma, trauma, abscess, ischemia, and infarction, among others. As a result, mainly motor deficits, sensory loss, and pain were reported. Many authors reported delayed treatments to resolve Anaes-SCI. Despite the potential complications, neuraxial techniques are still one of the best options for opioid-sparing pain prevention and management, reducing patients' morbidity, improving outcomes, reducing the length of hospital stay, and pain chronification, with a consequent economic benefit. The main findings of this review highlight the importance of careful patient management and close monitoring during neuraxial anaesthesia procedures to minimise the risk of spinal cord injury and complications.
Topics: Humans; Anesthesia, Spinal; Anesthesia, Epidural; Spinal Cord Injuries; Pain
PubMed: 36902095
DOI: 10.3390/ijms24054665 -
Frontiers in Pediatrics 2023This systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of... (Review)
Review
AIM
This systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies.
METHODS
We searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using "Covidence" systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment.
RESULTS
Data were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis.
CONCLUSION
We explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.
PubMed: 36896405
DOI: 10.3389/fped.2023.1071889 -
Frontiers in Aging Neuroscience 2023Physical exercise has been widely identified as a supplementary therapy for Parkinson's disease (PD). Evaluating changes in motor function over long-term periods of...
UNLABELLED
Physical exercise has been widely identified as a supplementary therapy for Parkinson's disease (PD). Evaluating changes in motor function over long-term periods of exercise and comparing efficacy of various exercise types will enable a better understanding of the effects of exercise on PD. In the current study, a total of 109 studies that covered 14 types of exercise were included in the analyses, enrolling 4,631 PD patients. The results of meta-regression revealed that chronic exercise delays the progression of PD motor symptoms, mobility, and balance decline deterioration, whereas for the non-exercise PD groups, motor function progressively decline. Results from network meta-analyses suggest that dancing is the optimal exercise for general motor symptoms of PD. Furthermore, Nordic walking is the most efficient exercise to mobility and balance performance. The results from network meta-analyses also suggest that Qigong may have specific benefit in improving hand function. The findings of the current study provide further evidence that chronic exercise preserves the progression of motor function decline in PD and suggest that dancing, yoga, multimodal training, Nordic walking, aquatic training, exercise gaming, and Qigong are effective PD exercises.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=276264, identifier: CRD42021276264.
PubMed: 36865410
DOI: 10.3389/fnagi.2023.1071803 -
International Journal of Molecular... Jan 2023PURA-related neurodevelopmental disorders (PURA-NDDs) are a rare genetic disease caused by pathogenic autosomal dominant variants in the PURA gene or a deletion... (Review)
Review
PURA-related neurodevelopmental disorders (PURA-NDDs) are a rare genetic disease caused by pathogenic autosomal dominant variants in the PURA gene or a deletion encompassing the PURA gene. PURA-NDD is clinically characterized by neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements, and epilepsy. It is generally considered to be central nervous system disorders, with generalized weakness, associated hypotonia, cognitive and development deficits in early development, and seizures in late stages. Although it is classified predominantly as a central nervous syndrome disorder, some phenotypic features, such as myopathic facies, respiratory insufficiency of muscle origin, and myopathic features on muscle biopsy and electrodiagnostic evaluation, point to a peripheral (neuromuscular) source of weakness. Patients with PURA-NDD have been increasingly identified in exome-sequenced cohorts of patients with neuromuscular- and congenital myasthenic syndrome-like phenotypes. Recently, fluctuating weakness noted in a PURA-NDD patient, accompanied by repetitive nerve stimulation abnormalities, suggested the disease to be a channelopathy and, more specifically, a neuromuscular junction disorder. Treatment with pyridostigmine or salbutamol led to clinical improvement of neuromuscular function in two reported cases. The goal of this systematic retrospective review is to highlight the motor symptoms of PURA-NDD, to further describe the neuromuscular phenotype, and to emphasize the role of potential treatment opportunities of the neuromuscular phenotype in the setting of the potential role of PURA protein in the neuromuscular junction and the muscles.
Topics: Humans; Neuromuscular Junction; Myasthenic Syndromes, Congenital; Neurodevelopmental Disorders; Learning Disabilities; Epilepsy; Muscle Hypotonia; Nervous System Malformations; DNA-Binding Proteins; Transcription Factors
PubMed: 36768582
DOI: 10.3390/ijms24032260 -
The Journal of Hand Surgery Mar 2023Restoration of elbow flexion is an important goal in the treatment of patients with traumatic brachial plexus injury. Numerous studies have described various nerve... (Meta-Analysis)
Meta-Analysis
PURPOSE
Restoration of elbow flexion is an important goal in the treatment of patients with traumatic brachial plexus injury. Numerous studies have described various nerve transfers for neurotization of the musculocutaneous nerve (or its motor branches); however, there is uncertainty over the effectiveness of each method. The aim of this study was to summarize the published evidence in adults with traumatic brachial plexus injury.
METHODS
Medline, Embase, medRxiv, and bioRxiv were systematically searched from inception to April 12, 2021. We included studies that reported the outcomes of nerve transfers for the restoration of elbow flexion in adults. The primary outcome was elbow flexion of grade 4 (M4) or higher on the British Medical Research Council scale. Data were pooled using random-effects meta-analyses, and heterogeneity was explored using metaregression. Confidence intervals (CIs) were generated to the 95% level.
RESULTS
We included 64 articles, which described 13 different nerve transfers. There were 1,335 adults, of whom 813 (61%) had partial and 522 (39%) had pan-plexus injuries. Overall, 75% of the patients with partial brachial plexus injuries achieved ≥M4 (CI, 69%-80%), and the choice of donor nerve was associated with clinically meaningful differences in the outcome. Of the patients with pan-plexus injuries, 45% achieved ≥M4 (CI, 31%-60%), and overall, each month delay from the time of injury to reconstruction reduced the probability of achieving ≥M4 by 7% (CI, 1%-12%).
CONCLUSIONS
The choice of donor nerve affects the chance of attaining a British Medical Research Council score of ≥4 in upper-trunk reconstruction. For patients with pan-plexus injuries, delay in neurotization may be detrimental to motor outcomes.
TYPE OF STUDY/LEVEL OF EVIDENCE
Therapeutic IV.
Topics: Humans; Adult; Nerve Transfer; Elbow; Brachial Plexus; Elbow Joint; Musculocutaneous Nerve; Brachial Plexus Neuropathies; Range of Motion, Articular; Treatment Outcome; Recovery of Function
PubMed: 36623945
DOI: 10.1016/j.jhsa.2022.11.013 -
Clinical and Experimental Pediatrics Jan 2023Myelomeningocele is a lifelong condition that features several comorbidities, such as hydrocephalus, scoliosis, club foot, and lower limb sensory and motor disabilities....
BACKGROUND
Myelomeningocele is a lifelong condition that features several comorbidities, such as hydrocephalus, scoliosis, club foot, and lower limb sensory and motor disabilities. Its management has progressed over time, ranging from supportive care to early postnatal closure to prenatal closure of the defect. Recent research discovered that fetal myelomeningocele closure (fMMC) provided superior neurological outcomes to those of postnatal closure. When performed at 12 months of age, fMMC can avert or delay the need for a ventriculoperitoneal shunt and reversed the hindbrain herniation. Moreover, fMMC reportedly enhanced motor function and mental development at 30 months of age. However, its long-term outcomes remain dubious.
PURPOSE
This systematic review aimed to determine the long-term neurological cognitive, behavioral, functional, and quality of life (QoL) outcomes after fMMC.
METHODS
The PubMed, Directory of Open Access Journals, EBSCO, and Cochrane databases were extensively searched for articles published in 2007-2022. Meta-analyses, clinical trials, and randomized controlled trials with at least 5 years of follow-up were given priority.
RESULTS
A total of 11 studies were included. Most studies revealed enhanced long-term cognitive, behavioral, functional, and QoL outcomes after fMMC.
CONCLUSION
Our results suggest that fMMC substantially enhanced patients' long-term neurological cognitive, behavioral, functional, and QoL outcomes.
PubMed: 36470279
DOI: 10.3345/cep.2022.01102 -
Emergency Medicine Journal : EMJ May 2023Prereduction radiographs are conventionally used to exclude fracture before attempts to reduce a dislocated shoulder in the ED. However, this step increases cost,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prereduction radiographs are conventionally used to exclude fracture before attempts to reduce a dislocated shoulder in the ED. However, this step increases cost, exposes patients to ionising radiation and may delay closed reduction. Some studies have suggested that prereduction imaging may be omitted for a subgroup of patients with shoulder dislocations.
OBJECTIVES
To determine whether clinical predictors can identify patients who may safely undergo closed reduction of a dislocated shoulder without prereduction radiographs.
METHODS
A systematic review and meta-analysis of diagnostic test accuracy studies that have evaluated the ability of clinical features to identify concomitant fractures in patients with shoulder dislocation. The search was updated to 23 June 2022 and language limits were not applied. All fractures were included except for Hill-Sachs lesions. Quality assessment was undertaken using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data were pooled and meta-analysed by fitting univariate random effects and multilevel mixed effects logistic regression models.
RESULTS
Eight studies reported data on 2087 shoulder dislocations and 343 concomitant fractures. The most important potential sources of bias were unclear blinding of those undertaking the clinical (6/8 studies) and radiographic (3/8 studies) assessment. The prevalence of concomitant fracture was 17.5%. The most accurate clinical predictors were age >40 (positive likelihood ratio (LR+) 1.8, 95% CI 1.5 to 2.1; negative likelihood ratio (LR-) 0.4, 95% CI 0.2 to 0.6), female sex (LR+ 2.0, 95% CI 1.6 to 2.4; LR- 0.7, 95% CI 0.6 to 0.8), first-time dislocation (LR+ 1.7, 95% CI 1.4 to 2.0; LR- 0.2, 95% CI 0.1 to 0.5) and presence of humeral ecchymosis (LR+ 3.0-5.7, LR- 0.8-1.1). The most important mechanisms of injury were high-energy mechanism fall (LR+ 2.0-9.8, LR- 0.4-0.8), fall >1 flight of stairs (LR+ 3.8, 95% CI 0.6 to 13.1; LR- 1.0, 95% CI 0.9 to 1.0) and motor vehicle collision (LR+ 2.3, 95% CI 0.5 to 4.0; LR- 0.9, 95% CI 0.9 to 1.0). The Quebec Rule had a sensitivity of 92.2% (95% CI 54.6% to 99.2%) and a specificity of 33.3% (95% CI 23.1% to 45.3%), but the Fresno-Quebec rule identified all clinically important fractures across two studies: sensitivity of 100% (95% CI 89% to 100%) in the derivation dataset and 100% (95% CI 90% to 100%) in the validation study. The specificity of the Fresno-Quebec rule ranged from 34% (95% CI 28% to 41%) in the derivation dataset to 24% (95% CI 16% to 33%) in the validation study.
CONCLUSION
Clinical prediction rules may have a role in supporting shared decision making after shoulder dislocation, particularly in the prehospital and remote environments when delay to imaging is anticipated.
Topics: Humans; Female; Shoulder Dislocation; Shoulder; Fractures, Bone; Radiography; Diagnostic Tests, Routine
PubMed: 36450522
DOI: 10.1136/emermed-2022-212696