There is a complex interrelation between epilepsy and cardiac pathology, with both acute and long-term effects of seizures on the regulation of the cardiac rhythm and on the heart functioning. A specific issue is the potential relation between these cardiac manifestations and the risk of Sudden and Unexpected Death in Epilepsy (SUDEP), with unclear respective role of centrally-control ictal changes, long-term epilepsy-related dysregulation of the neurovegetative control and direct effects on the heart function. In the present review, we detailed available data about ictal cardiac changes, along with interictal cardiac manifestations associated with long-term functional and structural alterations of the heart. Pathophysiological mechanisms of these cardiac changes are discussed, with a specific focus on central mechanisms and the investigation of a possible deregulation of the central control of autonomic functions in addition to the role of catecholamine and hypoxemia on heart.
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gold |
citations | 31 | |
popularity | Top 10% | |
influence | Top 10% | |
impulse | Top 10% |
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This review focuses on the use of resting-state functional magnetic resonance imaging data to assess functional connectivity in the human brain and its application in intractable epilepsy. This approach has the potential to predict outcomes for a given surgical procedure based on the pre-surgical functional organization of the brain. Functional connectivity can also identify cortical regions that are organized differently in epilepsy patients either as a direct function of the disease or through indirect compensatory responses. Functional connectivity mapping may help identify epileptogenic tissue, whether this is a single focal location or a network of seizure-generating tissues. This review covers the basics of connectivity analysis and discusses particular issues associated with analyzing such data. These issues include how to define nodes, as well as differences between connectivity analyses of individual nodes, groups of nodes, and whole-brain assessment at the voxel level. The need for arbitrary thresholds in some connectivity analyses is discussed and a solution to this problem is reviewed. Overall, functional connectivity analysis is becoming an important tool for assessing functional brain organization in epilepsy.
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gold |
citations | 53 | |
popularity | Top 10% | |
influence | Top 10% | |
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Over the last 30 years, the functions (and dysfunctions) of the sensory-motor circuitry have been mostly conceptualized using linear modelizations which have resulted in two main models: the "rate hypothesis" and the "oscillatory hypothesis." In these two models, the basal ganglia data stream is envisaged as a random temporal combination of independent simple patterns issued from its probability distribution of interval interspikes or its spectrum of frequencies respectively. More recently, non-linear analyses have been introduced in the modelization of motor circuitry activities, and they have provided evidences that complex temporal organizations exist in basal ganglia neuronal activities. Regarding movement disorders, these complex temporal organizations in the basal ganglia data stream differ between conditions (i.e., parkinsonism, dyskinesia, healthy control) and are responsive to treatments (i.e., l-DOPA, deep brain stimulation). A body of evidence has reported that basal ganglia neuronal entropy (a marker for complexity/irregularity in time series) is higher in hypokinetic state. In line with these findings, an entropy-based model has been recently formulated to introduce basal ganglia entropy as a marker for the alteration of motor processing and a factor of motor inhibition. Importantly, non-linear features have also been identified as a marker of condition and/or treatment effects in brain global signals (EEG), muscular activities (EMG), or kinetic of motor symptoms (tremor, gait) of patients with movement disorders. It is therefore warranted that the non-linear dynamics of motor circuitry will contribute to a better understanding of the neuronal dysfunctions underlying the spectrum of parkinsonian motor symptoms including tremor, rigidity, and hypokinesia.
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gold |
citations | 24 | |
popularity | Top 10% | |
influence | Average | |
impulse | Average |
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General and central nervous system anatomy and physiology in children is different to that of adults and this is relevant to traumatic brain injury (TBI) and spinal cord injury. The controversies and uncertainties in adult neurotrauma are magnified by these differences, the lack of normative data for children, the scarcity of pediatric studies, and inappropriate generalization from adult studies. Cerebral metabolism develops rapidly in the early years, driven by cortical development, synaptogenesis, and rapid myelination, followed by equally dramatic changes in baseline and stimulated cerebral blood flow. Therefore, adult values for cerebral hemodynamics do not apply to children, and children cannot be easily approached as a homogenous group, especially given the marked changes between birth and age 8. Their cranial and spinal anatomy undergoes many changes, from the presence and disappearance of the fontanels, the presence and closure of cranial sutures, the thickness and pliability of the cranium, anatomy of the vertebra, and the maturity of the cervical ligaments and muscles. Moreover, their systemic anatomy changes over time. The head is relatively large in young children, the airway is easily compromised, the chest is poorly protected, the abdominal organs are large. Physiology changes-blood volume is small by comparison, hypothermia develops easily, intracranial pressure (ICP) is lower, and blood pressure normograms are considerably different at different ages, with potentially important implications for cerebral perfusion pressure (CPP) thresholds. Mechanisms and pathologies also differ-diffuse injuries are common in accidental injury, and growing fractures, non-accidental injury and spinal cord injury without radiographic abnormality are unique to the pediatric population. Despite these clear differences and the vulnerability of children, the amount of pediatric-specific data in TBI is surprisingly weak. There are no robust guidelines for even basics aspects of care in children, such as ICP and CPP management. This is particularly alarming given that TBI is a leading cause of death in children. To address this, there is an urgent need for pediatric-specific clinical research. If this goal is to be achieved, any clinician or researcher interested in pediatric neurotrauma must be familiar with its unique pathophysiological characteristics.
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gold |
citations | 129 | |
popularity | Top 1% | |
influence | Top 10% | |
impulse | Top 1% |
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Although the scientific community has focused on the effects of concussions in contact sports, the role of subconcussive impacts, as it can occur during soccer heading, has recently gained attention, considering that it may represent an additional mechanism of cumulative brain injury. The aim of this study is to investigate the effects of soccer heading on cognitive functioning in active professional soccer players. Male soccer players (
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gold |
citations | 9 | |
popularity | Top 10% | |
influence | Average | |
impulse | Average |
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Introduction: Cognitive impairment and orthostatic hypotension (OH) are common, disabling Parkinson disease (PD) symptoms that are strongly correlated. Whether the relationship is causative or associative remains unknown. OH may occur without classic orthostatic symptoms of cerebral hypoperfusion (i.e., lightheadedness or dizziness). Whether longitudinal differences in cognition occur between symptomatic and asymptomatic OH patients has not been explored. Objectives: We characterized the prevalence of OH, orthostatic symptoms, and cognitive impairment among PD patients and compared cognition between patients with and without OH, and between patients with symptomatic and asymptomatic OH. Methods: Our cross-sectional, retrospective, observational study included 226 clinically diagnosed PD patients who underwent repeated standardized evaluations. Among these, 62 had longitudinal follow-up of > 3.5 years. We compared longitudinal Montreal Cognitive Assessment (MoCA) scores between patients remaining OH-free (n = 14) and those without baseline OH that developed OH (n = 28), matched for age, sex, education, and PD duration. We also compared MoCA scores between groups with asymptomatic OH (n = 13) and symptomatic OH (n = 13) matched for the same factors. Results: In the cross-sectional analysis, OH patients had worse cognition. In the longitudinal analysis (mean follow-up = 5.3 years), OH patients had worse cognitive decline (p = 0.027). Cognitive impairment was similar between asymptomatic and symptomatic OH patients in the cross-sectional and longitudinal analyses. Conclusions: OH is associated with cognitive impairment in PD. Further studies are needed in larger cohorts to expand our findings and to determine whether treating OH can prevent or delay cognitive dysfunction.
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Green | |
gold |
citations | 21 | |
popularity | Top 10% | |
influence | Average | |
impulse | Top 10% |
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In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson's disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved.
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Green | |
gold |
citations | 59 | |
popularity | Top 10% | |
influence | Top 10% | |
impulse | Top 10% |
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handle: 1959.13/1493245
IntroductionNeuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments.MethodsSystematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool.ResultsA total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of−0.27 (-0.37,−0.16) and−0.31(-0.46,−0.16), respectively.ConclusionThe off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424.
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Green | |
gold |
citations | 2 | |
popularity | Average | |
influence | Average | |
impulse | Average |
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Motor dysfunction in Parkinson's disease is believed to arise primarily from pathophysiology in the dorsal striatum and its related corticostriatal and thalamostriatal circuits during progressive dopamine denervation. One function of these circuits is to provide a filter that selectively facilitates or inhibits cortical activity to optimize cortical processing, making motor responses rapid and efficient. Corticostriatal synaptic plasticity mediates the learning that underlies this performance-optimizing filter. Under dopamine denervation, corticostriatal plasticity is altered, resulting in aberrant learning that induces inappropriate basal ganglia filtering that impedes rather than optimizes cortical processing. Human imaging suggests that increased cortical activity may compensate for striatal dysfunction in PD patients. In this Perspective article, we consider how aberrant learning at corticostriatal synapses may impair cortical processing and learning and undermine potential cortical compensatory mechanisms. Blocking or remediating aberrant corticostriatal plasticity may protect cortical function and support cortical compensatory mechanisms mitigating the functional decline associated with progressive dopamine denervation.
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gold |
citations | 33 | |
popularity | Top 10% | |
influence | Average | |
impulse | Top 10% |
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Survivors of infant traumatic brain injury (TBI) are prone to chronic neurological deficits that impose lifelong individual and societal burdens. Translation of novel interventions to clinical trials is hampered in part by the lack of truly representative preclinical tests of cognition and corresponding biomarkers of functional outcomes. To address this gap, the ability of a high-dose, extended, post-injury regimen of erythropoietin (EPO, 3000U/kg/dose × 6d) to prevent chronic cognitive and imaging deficits was tested in a postnatal day 12 (P12) controlled-cortical impact (CCI) model in rats, using touchscreen operant chambers and regional analysis of diffusion tensor imaging (DTI). Results indicate that EPO prevents functional injury and MRI injury after infant TBI. Specifically, subacute DTI at P30 revealed widespread microstructural damage that is prevented by EPO. Assessment of visual discrimination on a touchscreen operant chamber platform demonstrated that all groups can perform visual discrimination. However, CCI rats treated with vehicle failed to pass reversal learning, and perseverated, in contrast to sham and CCI-EPO rats. Chronic DTI at P90 showed EPO treatment prevented contralateral white matter and ipsilateral lateral prefrontal cortex damage. This DTI improvement correlated with cognitive performance. Taken together, extended EPO treatment restores executive function and prevents microstructural brain abnormalities in adult rats with cognitive deficits in a translational preclinical model of infant TBI. Sophisticated testing with touchscreen operant chambers and regional DTI analyses may expedite translation and effective yield of interventions from preclinical studies to clinical trials. Collectively, these data support the use of EPO in clinical trials for human infants with TBI.
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gold |
citations | 23 | |
popularity | Top 10% | |
influence | Average | |
impulse | Top 10% |
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There is a complex interrelation between epilepsy and cardiac pathology, with both acute and long-term effects of seizures on the regulation of the cardiac rhythm and on the heart functioning. A specific issue is the potential relation between these cardiac manifestations and the risk of Sudden and Unexpected Death in Epilepsy (SUDEP), with unclear respective role of centrally-control ictal changes, long-term epilepsy-related dysregulation of the neurovegetative control and direct effects on the heart function. In the present review, we detailed available data about ictal cardiac changes, along with interictal cardiac manifestations associated with long-term functional and structural alterations of the heart. Pathophysiological mechanisms of these cardiac changes are discussed, with a specific focus on central mechanisms and the investigation of a possible deregulation of the central control of autonomic functions in addition to the role of catecholamine and hypoxemia on heart.
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gold |
citations | 31 | |
popularity | Top 10% | |
influence | Top 10% | |
impulse | Top 10% |
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This review focuses on the use of resting-state functional magnetic resonance imaging data to assess functional connectivity in the human brain and its application in intractable epilepsy. This approach has the potential to predict outcomes for a given surgical procedure based on the pre-surgical functional organization of the brain. Functional connectivity can also identify cortical regions that are organized differently in epilepsy patients either as a direct function of the disease or through indirect compensatory responses. Functional connectivity mapping may help identify epileptogenic tissue, whether this is a single focal location or a network of seizure-generating tissues. This review covers the basics of connectivity analysis and discusses particular issues associated with analyzing such data. These issues include how to define nodes, as well as differences between connectivity analyses of individual nodes, groups of nodes, and whole-brain assessment at the voxel level. The need for arbitrary thresholds in some connectivity analyses is discussed and a solution to this problem is reviewed. Overall, functional connectivity analysis is becoming an important tool for assessing functional brain organization in epilepsy.