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Frontiers in Neurology 2023The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD...
BACKGROUND/OBJECTIVES
The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD in adults is difficult, because phenotypes are different from those in children and influenced by symptoms from acquired conditions. This systematic literature review aims to answer the following questions: (1) What is the diagnostic yield of exome/genome sequencing (ES/GS) for IMD in adults with unsolved phenotypes? (2) What characteristics do adult patients diagnosed with IMD through ES/GS have?
METHODS
A systematic search was conducted using the following search terms (simplified): "Whole exome sequencing (WES)," "Whole genome sequencing (WGS)," "IMD," "diagnostics" and the 1,450 known metabolic genes derived from ICIMD. Data from 695 articles, including 27,702 patients, were analyzed using two different methods. First, the diagnostic yield for IMD in patients presenting with a similar phenotype was calculated. Secondly, the characteristics of patients diagnosed with IMD through ES/GS in adulthood were established.
RESULTS
The diagnostic yield of ES and/or GS for adult patients presenting with unexplained neurological symptoms is 11% and for those presenting with dyslipidemia, diabetes, auditory and cardiovascular symptoms 10, 9, 8 and 7%, respectively. IMD patients diagnosed in adulthood (n = 1,426), most frequently portray neurological symptoms (65%), specifically extrapyramidal/cerebellar symptoms (57%), intellectual disability/dementia/psychiatric symptoms (41%), pyramidal tract symptoms/myelopathy (37%), peripheral neuropathy (18%), and epileptic seizures (16%). The second most frequently observed symptoms were ophthalmological (21%). In 47% of the IMD diagnosed patients, symptoms from multiple organ systems were reported. On average, adult patients are diagnosed 15 years after first presenting symptoms. Disease-related abnormalities in metabolites in plasma, urine or cerebral spinal fluid were identified in 40% of all patients whom underwent metabolic screening. In 52% the diagnosis led to identification of affected family members with the same IMD.
CONCLUSION
ES and/or GS is likely to yield an IMD diagnosis in adult patients presenting with an unexplained neurological phenotype, as well as in patients with a phenotype involving multiple organ systems. If a gene panel does not yield a conclusive diagnosis, it is worthwhile to analyze all known disease genes. Further prospective research is needed to establish the best diagnostic approach (type and sequence of metabolic and genetic test) in adult patients presenting with a wide range of symptoms, suspected of having an IMD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021295156.
PubMed: 37560457
DOI: 10.3389/fneur.2023.1206106 -
Neuroscience and Biobehavioral Reviews Sep 2023Neural adaptations to resistance training (RT) and their correlation with muscle strength remain partially understood. We conducted a systematic review and multivariate... (Meta-Analysis)
Meta-Analysis Review
Neural adaptations to resistance training (RT) and their correlation with muscle strength remain partially understood. We conducted a systematic review and multivariate meta-analysis to examine the effects of metronome-paced (MP), self-paced (SP), and isometric (IM) training on M1 and corticospinal pathway activity. Following MP RT, a significant increase in corticospinal excitability was observed, correlating with increased strength. Conversely, no significant relationship was found after SP or IM training. RT also reduced the duration of the cortical silent period, but this change did not predict strength changes and was not specific to any training modality. No significant effects were found for short-interval intracortical inhibition. Our findings suggest that changes in corticospinal excitability may contribute to strength gains after RT. Furthermore, the relationship between these adaptations and strength appears dependent on the type of training performed.
Topics: Humans; Resistance Training; Pyramidal Tracts; Transcranial Magnetic Stimulation; Motor Cortex; Muscle Strength; Evoked Potentials, Motor; Muscle, Skeletal
PubMed: 37353049
DOI: 10.1016/j.neubiorev.2023.105289 -
Journal of Stroke Jan 2016Early evaluation of the pyramidal tract using Diffusion Tensor Imaging (DTI) is a prerequisite to decide the optimal treatment or to assess appropriate rehabilitation.... (Review)
Review
Early evaluation of the pyramidal tract using Diffusion Tensor Imaging (DTI) is a prerequisite to decide the optimal treatment or to assess appropriate rehabilitation. The early predictive value of DTI for assessing motor and functional recovery in ischemic stroke (IS) has yielded contradictory results. The purpose is to systematically review and summarize the current available literature on the value of Fractional Anisotropy (FA) parameter of the DTI in predicting upper limb motor recovery after sub-acute IS. MEDLINE, PubMed, EMBASE, Google Scholar and Cochrane CENTRAL searches were conducted from January 1, 1950, to July 31, 2015, which was supplemented with relevant articles identified in the references. Correlation between FA and upper limb motor recovery measure was done. Heterogeneity was examined using Higgins I-squared, Tau-squared. Summary of correlation coefficient was determined using Random Effects model. Out of 166 citations, only eleven studies met the criteria for inclusion in the systematic review and six studies were included in the meta-analysis. A random effects model revealed that DTI parameter FA is a significant predictor for upper limb motor recovery after sub-acute IS [Correlation Coefficient=0.82; 95% Confidence Interval-0.66 to 0.90, P value<0.001]. Moderate heterogeneity was observed (Tau-squared=0.12, I-squared=62.14). The studies reported so far on correlation between DTI and upper limb motor recovery are few with small sample sizes. This meta-analysis suggests strong correlation between DTI parameter FA and upper limb motor recovery. Well-designed prospective trials embedded with larger sample size are required to establish these findings.
PubMed: 26846758
DOI: 10.5853/jos.2015.01186 -
Frontiers in Human Neuroscience 2021Swallowing disorders (dysphagia) can negatively impact quality of life and health. For clinicians and researchers seeking to improve outcomes for patients with...
Swallowing disorders (dysphagia) can negatively impact quality of life and health. For clinicians and researchers seeking to improve outcomes for patients with dysphagia, understanding the neural control of swallowing is critical. The role of gray matter in swallowing control has been extensively documented, but knowledge is limited regarding the contributions of white matter. Our aim was to identify, evaluate, and summarize the populations, methods, and results of published articles describing the role of white matter in neural control of swallowing. We completed a systematic review with a multi-engine search following PRISMA-P 2015 standards. Two authors screened articles and completed blind full-text review and quality assessments using an adapted U.S. National Institute of Health's Quality Assessment. The senior author resolved any disagreements. Qualitative synthesis of evidence was completed. The search yielded 105 non-duplicate articles, twenty-two of which met inclusion criteria. Twenty were rated as Good (5/22; 23%) or Fair (15/22; 68%) quality. Stroke was the most represented diagnosis ( = 20; 91%). All studies were observational, and half were retrospective cohort design. The majority of studies (13/22; 59%) quantified white matter damage with lesion-based methods, whereas 7/22 (32%) described intrinsic characteristics of white matter using methods like fractional anisotropy. Fifteen studies (68%) used instrumental methods for swallowing evaluations. White matter areas commonly implicated in swallowing control included the pyramidal tract, internal capsule, corona radiata, superior longitudinal fasciculus, external capsule, and corpus callosum. Additional noteworthy themes included: severity of white matter damage is related to dysphagia severity; bilateral white matter lesions appear particularly disruptive to swallowing; and white matter adaptation can facilitate dysphagia recovery. Gaps in the literature included limited sample size and populations, lack of in-depth evaluations, and issues with research design. Although traditionally understudied, there is sufficient evidence to conclude that white matter is critical in the neural control of swallowing. The reviewed studies indicated that white matter damage can be directly tied to swallowing deficits, and several white matter structures were implicated across studies. Further well-designed interdisciplinary research is needed to understand white matter's role in neural control of normal swallowing and in dysphagia recovery and rehabilitation.
PubMed: 34262441
DOI: 10.3389/fnhum.2021.628424 -
Developmental Medicine and Child... Aug 2012Structural connectivity analysis using diffusion magnetic resonance imaging (dMRI) and tractography has become the method of choice for studying white matter pathology... (Review)
Review
AIM
Structural connectivity analysis using diffusion magnetic resonance imaging (dMRI) and tractography has become the method of choice for studying white matter pathology and reorganization in children with congenital hemiplegia. To evaluate its role in the research domain, we systematically reviewed the literature about children with cerebral palsy (CP) to document common findings and identify strengths and possible limitations of this neuroimaging technology.
METHOD
A literature search was performed for peer-reviewed studies pertaining to dMRI and CP.
RESULTS
Twenty-two studies met the inclusion criteria. The corticospinal tract was studied in greatest detail (18/22). The most common finding was decreased fractional anisotropy and/or increased mean diffusivity, indicating significant loss in the integrity of these corticomotor pathways. Fewer studies assessed ascending sensorimotor pathways including the posterior and superior thalamic radiations, which also showed decreased fractional anisotropy. Anisotropy indices (fractional anisotropy, mean diffusivity) obtained for both corticomotor and sensorimotor tracts were repeatedly shown to correlate with clinical measures. Other tracts studied included commissural and association fibres, which showed conflicting results.
INTERPRETATION
There is sound evidence that dMRI-based connectivity techniques are useful for improving our understanding of the structure-function relationships of corticomotor and sensorimotor neural networks in CP.
Topics: Cerebral Palsy; Child; Diffusion Magnetic Resonance Imaging; Humans; Pyramidal Tracts
PubMed: 22646844
DOI: 10.1111/j.1469-8749.2012.04332.x -
Scientific Reports Jul 2021The usefulness of magnetic resonance imaging (MRI) in predicting gait ability in stroke patients remains unclear. Therefore, MRI evaluations have not yet been...
The usefulness of magnetic resonance imaging (MRI) in predicting gait ability in stroke patients remains unclear. Therefore, MRI evaluations have not yet been standardized in stroke rehabilitation. We performed a systematic review to consolidate evidence regarding the use of MRIs in predicting gait ability of stroke patients. The Medline, Cumulative Index to Nursing and Allied Health Literature, and SCOPUS databases were comprehensively searched. We included all literature published from each source's earliest date to August 2020. We included 19 studies: 8 were classified as structure- or function-based MRI studies and 11 as neural tract integrity-based MRI studies. Most structure- or function-based MRI studies indicated that damage to motor-related areas (primary motor cortex, corona radiata, internal capsule, and basal ganglia) or insula was related to poor gait recovery. In neural tract integrity-based MRI studies, integrity of the corticospinal tract was related to gait ability. Some studies reported predictive value of the corticoreticular pathway. All included studies had some concerns, at least one, based on the Cochrane risk of bias instrument. This review suggests that MRIs are useful in predicting gait ability of stroke patients. However, we cannot make definitive conclusion regarding the predictive value, due to the lack of quantitative evaluations.
Topics: Gait; Humans; Magnetic Resonance Imaging; Pyramidal Tracts; Stroke; Stroke Rehabilitation
PubMed: 34253774
DOI: 10.1038/s41598-021-93717-4 -
Brain Stimulation 2019Over the past decade several studies have shown that transcranial alternating current stimulation (tACS) delivered at the beta (15-25 Hz) frequency range can increase... (Meta-Analysis)
Meta-Analysis
Over the past decade several studies have shown that transcranial alternating current stimulation (tACS) delivered at the beta (15-25 Hz) frequency range can increase corticospinal excitability of the primary motor cortex (M1). The aim of this study was to systematically quantify the effect size of beta-tACS on corticospinal excitability in healthy volunteers, as well as to identify significant outcome predictors. A meta-analysis was performed on the results of 47 experiments reported in 21 studies. Random effects modelling of the effect sizes showed that beta-tACS significantly increases M1 excitability (Ē = 0.287, 95% CI = 0.133-0.440). Further analysis showed that tACS intensities above 1 mA peak-to-peak yield a robust increase in M1 excitability, whereas intensities of 1 mA peak-to-peak and below do not induce a reliable change. Additionally, results showed an impact of tACS montages on these effects. No difference in effect size for online compared to offline application of tACS was found. In conclusion, these findings indicate that beta-tACS can increase cortical excitability if stimulation intensity is above 1 mA, yet more research is needed to titrate the stimulation parameters that yield optimal results.
Topics: Cortical Excitability; Evoked Potentials, Motor; Humans; Motor Cortex; Pyramidal Tracts; Transcranial Direct Current Stimulation
PubMed: 31405789
DOI: 10.1016/j.brs.2019.07.023 -
Frontiers in Neuroscience 2019Hereditary spastic paraplegia (HSP) and hereditary ataxia (HA) are two groups of disorders characterized, respectively, by progressive dysfunction or degeneration of the...
Hereditary spastic paraplegia (HSP) and hereditary ataxia (HA) are two groups of disorders characterized, respectively, by progressive dysfunction or degeneration of the pyramidal tracts (HSP) and of the Purkinje cells and spinocerebellar tracts (HA). Although HSP and HA are generally shown to have distinct clinical-genetic profiles, in several cases the clinical presentation, the causative genes, and the cellular pathways and mechanisms involved overlap between the two forms. Genetic analyses in humans in combination with and studies using model systems have greatly expanded our knowledge of spinocerebellar degenerative disorders. In this review, we focus on the zebrafish (), a vertebrate model widely used in biomedical research since its overall nervous system organization is similar to that of humans. A critical analysis of the literature suggests that zebrafish could serve as a powerful experimental tool for molecular and genetic dissection of both HA and HSP. The zebrafish, found to be very useful for demonstrating the causal relationship between defect and mutation, also offers a useful platform to exploit for the development of therapies.
PubMed: 31920481
DOI: 10.3389/fnins.2019.01311 -
Journal of Huntington's Disease 2020Corticobulbar symptoms have been reported in all stages of Huntington's disease (HD); aspiration pneumonia associated with swallowing impairment has been identified as...
BACKGROUND
Corticobulbar symptoms have been reported in all stages of Huntington's disease (HD); aspiration pneumonia associated with swallowing impairment has been identified as the most common cause of death. Whilst recent research has described positive effects of corticobulbar rehabilitation in other neurodegenerative conditions, it is unclear if this is similarly effective in HD. Preliminary evidence in corticospinal rehabilitation has revealed physical therapy and exercise could be beneficial for individuals with HD.
OBJECTIVE
This systematic review will explore the literature relative to rehabilitation of corticobulbar symptoms in adults with HD.
METHODS
Two investigators independently searched relevant electronic databases for literature related to corticobulbar rehabilitation in HD, published in English until October 2019. Included studies were critically appraised using the Oxford Centre for Evidence-based Medicine Levels of Evidence, Cochrane Risk of Bias Tool and Scottish Intercollegiate Guidelines Network checklists. Study outcomes included measurements of function, quality of life or neuromuscular physiology.
RESULTS
Seventy-seven publications were screened with eight studies meeting the inclusion criteria - two randomised control trials and six intervention studies. Validated and objective outcome measures of corticobulbar symptoms were infrequently used. There was a high risk of bias identified in 7/8 studies. The data suggested positive clinical outcomes, no adverse effects and no deterioration observed across longitudinal studies.
CONCLUSIONS
This systematic review documented a lack of high-quality evidence to support the use of rehabilitation to treat corticobulbar symptoms in HD. However, the suggestion of potential positive effects based on available, albeit limited, studies provides justification for further research in this area.
Topics: Deglutition Disorders; Dysarthria; Humans; Huntington Disease; Outcome Assessment, Health Care; Pyramidal Tracts
PubMed: 31744013
DOI: 10.3233/JHD-190384 -
Journal of Sport and Health Science Mar 2021To examine the effect of anterior cruciate ligament (ACL) reconstruction on spinal-reflex and corticospinal excitability of the quadriceps muscle. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effect of anterior cruciate ligament (ACL) reconstruction on spinal-reflex and corticospinal excitability of the quadriceps muscle.
METHODS
A comprehensive electronic database search was performed to identify studies that objectively measured Hoffmann reflex to muscle response ratio, motor threshold, and motor evoked potentials after ACL reconstruction. Pooled standardized mean differences (SMDs) were computed using a random effects meta-analysis model.
RESULTS
A total of 13 studies were eligible for analysis. The Hoffmann reflex to muscle response ratio was significantly higher on both the reconstructed and non-reconstructed legs when compared with the healthy control leg (SMD = 0.28, 95% confidence interval (95%CI): 0.08-0.49, p = 0.006 and SMD = 0.22, 95%CI: 0.04-0.40, p = 0.016, respectively) but did not differ between legs (SMD = 0.10, 95%CI: -0.01 to 0.21, p = 0.078). The motor threshold was significantly higher on both the reconstructed (SMD = 0.76, 95%CI: 0.40-1.12, p < 0.001) and non-reconstructed legs (SMD = 0.47, 95%CI: 0.00-0.95, p = 0.049) when compared with the legs of healthy controls. The reconstructed leg also had a higher motor threshold when compared with the non-reconstructed leg (SMD = 0.20, 95%CI: 0.06-0.34, p = 0.005). These changes were paralleled by bilateral reductions in quadriceps strength (ACL reconstructed: SMD = -0.78, 95%CI: -1.07 to -0.49, p < 0.001; non-reconstructed: SMD = -0.32, 95%CI: -0.63 to -0.01, p = 0.042) and quadriceps voluntary activation (ACL reconstructed: SMD = -0.73, 95%CI: -0.97 to -0.50, p < 0.001; non-reconstructed: SMD = -0.55, 95%CI: -0.82 to -0.27, p < 0.001) when compared with healthy controls.
CONCLUSION
There is increased excitability of the spinal-reflex pathways and reduced excitability of the corticospinal pathways following ACL reconstruction. These changes are paralleled by reductions in quadriceps strength and voluntary activation, suggesting that rehabilitation interventions should focus on normalizing the excitability of neural pathways to effectively address quadriceps dysfunction after ACL reconstruction.
Topics: Anterior Cruciate Ligament Reconstruction; Bias; Brain; Confidence Intervals; Evoked Potentials, Motor; Humans; Muscle Contraction; Muscle Strength; Pyramidal Tracts; Quadriceps Muscle; Reflex; Sensory Thresholds; Spinal Cord
PubMed: 32707098
DOI: 10.1016/j.jshs.2020.07.005