Impaired Neuromuscular Coordination Research Articles

Phosphodiesterase 5 (PDE-5) inhibitors (sildenafil, tadalafil, and vardenafil) effects on esophageal motility: a systematic review

BackgroundEsophageal motility disorders are a group of disorders associated with dysfunctional swallowing resulting from impaired neuromuscular coordination. Phosphodiesterase 5 (PDE-5) inhibitors induce smooth relaxation and are proposed as a treatment option for esophageal motility disorders such as achalasia.MethodsThis study is conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically searched MEDLINE/ PubMed, Scopus, EMBASE, and Web of Science databases for esophageal outcomes of individuals treated with PDE5 inhibitors. A random effect meta-analysis was conducted.ResultsA total of 14 studies were included. They were conducted in different countries, with Korea and Italy having the highest number of articles. The main drug assessed was sildenafil. PDE-5 inhibitors resulted in a significant reduction in lower esophageal sphincter pressure (SMD − 1.69, 95% CI: -2.39 to -0.99) and the amplitude of contractions (SMD − 2.04, 95% CI: -2.97 to -1.11). Residual pressure was not significantly different between the placebo and sildenafil groups (SMD − 0.24, 95% CI: -1.20 to 0.72). Furthermore, a recent study reported contractile integral, stating that ingestion of sildenafil leads to a significant reduction in distal contractile integral and a significant increase in proximal contractile integral.ConclusionPDE-5 inhibitors significantly reduce LES resting pressure and esophageal peristaltic vigor, decreasing esophageal body contractility and contraction reserve. Therefore, using these drugs in patients affected by esophageal motility disorders may potentially improve their condition regarding symptom relief and prevention of further associated complications. Future reports investigating larger sample size is necessary in order to establish definite evidence regarding the efficacy of these drugs.

COHERENCE NETWORKS OF BILATERAL UPPER LIMB MOTIONS IN CHRONIC STROKE PATIENTS

Understanding the mechanisms of how the skeletal system reduces multiple degrees of freedom in motor control is very important in the field of neurorehabilitation. We therefore need to understand the functional connectivity of these synergistic patterns in bilateral upper limb of stroke patients from different Brunnstrom Stages. The intermuscular coherence at different frequency bands is decomposed to obtain muscle synchronization. Muscle networks were then applied to describe the functional connectivity between muscle pairs. We recruited 35 stroke patients with Brunnstrom Stages III-VI. Muscle activity was acquired from seven muscles around forearm while participants performed voluntary upward reaching with both affected and unaffected sides. We decomposed IMC spectra by negative matrix factorization to identify shared frequencies and co-modulated muscles. Two muscle networks were found and functional muscle networks are evaluated by strength, transitivity and global efficiency. Results showed that the network topology was different significantly between the two sides and between Brunnstrom stages of stroke patients. These findings can throw light on the understanding of motor control and rehabilitation of motor impairment for stroke survivors, which may promote the post-stroke rehabilitation process by detecting impaired neuromuscular coordination in frequency domain.

Alterations in Muscle Networks in the Upper Extremity of Chronic Stroke Survivors.

Muscle networks describe the functional connectivity between muscles quantified through the decomposition of intermuscular coherence (IMC) to identify shared frequencies at which certain muscles are co-modulated by common neural input. Efforts have been devoted to characterizing muscle networks in healthy subjects but stroke-linked alterations to muscle networks remain unexplored. Muscle networks were assessed for eight key upper extremity muscles during isometric force generation in stroke survivors with mild, moderate, and severe impairment and compared against healthy controls to identify stroke-specificalterations in muscle connectivity. Coherence matrices were decomposed using non-negative matrix factorization. The variance accounted for thresholding was then assessed to identify the number of muscle networks. Results showed that the number of muscle networks decreased in stroke survivors compared to age-matched healthy controls (four networks in the healthy control group) as the severity of post-stroke motor impairment increased (three in the mild- and two in the moderate- and severe-strokegroups). Statistically significant reductions of IMC in the synergistic deltoid muscles in the alpha-band in stroke patients versus healthy controls ( p < 0.05) were identified. This study represents the first effort, to the best of our knowledge, to assess stroke-linked alterations in functional intermuscular connectivity using muscle network analysis. The findings revealed a pattern of alterations to muscle networks in stroke survivors compared to healthy controls, as a result of the loss of brain function associated with the stroke. These alterations in muscle networks reflected underlying pathophysiology. These findings can help better understand the motor impairment and motor control in stroke and may advance rehabilitation efforts for stroke by identifying the impaired neuromuscular coordination among multiple muscles in the frequency domain.

Clinical relevance of chronic neuropathic pain phenotypes in mice: A comprehensive behavioral analysis

Despite a large number of preclinical studies performed each year, the safe and effective therapeutic interventions for chronic pain are scant. Therefore, it appears that pre-clinical modeling requires a systematically organized behavioral test paradigm to quantify the response of animals for a specific pain state. The present study, therefore, conceptualized a test battery to evaluate the behavioral changes in mice following neuropathic pain. We employed sciatic nerve chronic constriction injury (CCI) in C57BL/6 J mice to model chronic pain state. Mice were monitored for thermal hyperalgesia and grip strength for 30 days. Subsequently, mice underwent a behavioral test battery consisting of the nociceptive threshold, the affective and cognitive functions and motor coordination, and strength. Our results showed that CCI mice are insensitive to thermal stimuli. However, nerve-injured mice showed significant changes in neuromuscular coordination, basal anxiety, and hedonic state. Such impaired neuromuscular coordination is indicative of disability rather than the actual pain phenotype. While using the digital gait analysis, our study revealed rationales for the insensitivity of CCI mice to thermal stimuli. Our results suggest that the predictive validity of the CCI model necessitates a comprehensive behavioral test battery to select the clinically relevant and measurable phenotype to quantify chronic neuropathic pain.

The loss of slow skeletal muscle isoform of troponin T in spindle intrafusal fibres explains the pathophysiology of Amish nemaline myopathy.

The pathogenic mechanism and the neuromuscular reflex-related phenotype (e.g. tremors accompanied by clonus) of Amish nemaline myopathy, as well as of other recessively inherited TNNT1 myopathies, remain to be clarified. The truncated slow skeletal muscle isoform of troponin T (ssTnT) encoded by the mutant TNNT1 gene is unable to incorporate into myofilaments and is degraded in muscle cells. By contrast to extrafusal muscle fibres, spindle intrafusal fibres of normal mice contain a significant level of cardiac TnT and a low molecular weight splice form of ssTnT. Intrafusal fibres of ssTnT-knockout mice have significantly increased cardiac TnT. Rotarod and balance beam tests have revealed abnormal neuromuscular co-ordination in ssTnT-knockout mice and a blunted response to a spindle sensitizer, succinylcholine. The loss of ssTnT and a compensatory increase of cardiac TnT in intrafusal nuclear bag fibres may increase myofilament Ca2+ -sensitivity and tension, impairing spindle function, thus identifying a novel mechanism for the development of targeted treatment. A nonsense mutation at codon Glu180 of TNNT1 gene causes Amish nemaline myopathy (ANM), a recessively inherited disease with infantile lethality. TNNT1 encodes the slow skeletal muscle isoform of troponin T (ssTnT). The truncated ssTnT is unable to incorporate into myofilament and is degraded in muscle cells. The symptoms of ANM include muscle weakness, atrophy, contracture and tremors accompanied by clonus. An ssTnT-knockout (KO) mouse model recapitulates key features of ANM such as atrophy of extrafusal slow muscle fibres and increased fatigability. However, the neuromuscular reflex-related symptoms of ANM have not been explained. By isolating muscle spindles from ssTnT-KO and control mice aiming to examine the composition of myofilament proteins, we found that, in contrast to extrafusal fibres, intrafusal fibres contain a significant level of cardiac TnT and the low molecular weight splice form of ssTnT. Intrafusal fibres from ssTnT-KO mice have significantly increased cardiac TnT. Rotarod and balance beam tests revealed impaired neuromuscular co-ordination in ssTnT-KO mice, indicating abnormality in spindle functions. Unlike the wild-type control, the beam running ability of ssTnT-KO mice had a blunted response to a spindle sensitizer, succinylcholine. Immunohistochemistry detected ssTnT and cardiac TnT in nuclear bag fibres, whereas fast skeletal muscle TnT was detected in nuclear chain fibres, and cardiac α-myosin was present in one of the two nuclear bag fibres. The loss of ssTnT and a compensatory increase of cardiac TnT in nuclear bag fibres would increase myofilament Ca2+ -sensitivity and tension, thus affecting spindle activities. This mechanism provides an explanation for the pathophysiology of ANM, as well as a novel target for treatment.

Effects of deep cervical flexor training on impaired physiological functions associated with chronic neck pain: a systematic review

BackgroundNeck pain is a major health issue with high rates of recurrence. It presents with a variety of altered sensorimotor functions. Exercise is a cornerstone of rehabilitation and many training methods are used. Exercise is evaluated in most randomized controlled trials on its pain relieving effects. No review has assessed the effect of exercise on the altered physiological functions or determined if there are differential effects of particular training methods. This review investigated the effects of deep cervical flexor (DCF) training, a training method commonly used for patients with neck pain, and compared it to other training methods or no training on outcomes of cervical neuromuscular function, muscle size, kinematics and kinetics.MethodsWeb of Science, Scopus, CINAHL, PubMed were searched from inception until January 2018. Twelve randomized controlled trials were included that compared DCF training as sole intervention to other training or no interventions in persons with neck pain. The Cochrane Risk of Bias tool was used to assess the method quality. All outcome measures were analysed descriptively and meta-analyses were performed for measures evaluated in three or more studies.ResultsDCF training was compared to cervical endurance, strength, proprioception and mobility training, muscle stretching, and no intervention control groups. Physiological outcome measures included neuromuscular co-ordination (craniocervical flexion test), functional tasks, muscle fatigability, muscle size, kinematics (joint position sense, posture and range of motion) and kinetics (strength, endurance and contraction accuracy). Strong evidence was found for effectiveness of DCF training on neuromuscular coordination, but it had no or small effects on strength and endurance at higher loads. DCF training improved head and cervical posture, while evidence was limited or contradictory for other measures.ConclusionsDCF training can successfully address impaired neuromuscular coordination, but not cervical flexor strength and endurance at higher contraction intensities. A multimodal training regime is proposed when the aim is to specifically address various impaired physiological functions associated with neck pain.

Biochemical, Histological, and Memory Impairment Effects of Chronic Copper Toxicity: A Model for Non-Wilsonian Brain Copper Toxicosis in Wistar Rat

Animal models of copper toxicosis rarely exhibit neurological impairments and increased brain copper accumulation impeding the development of novel therapeutic approaches to treat neurodegenerative diseases having high brain Cu content. The aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15mg Cu/100g body weight) daily for 90days on copper and zinc levels in the liver and hippocampus, on biochemical parameters, and on neurobehavioral functions (by Morris water maze) of male Wistar rats. Copper-administered animals exhibited significantly decreased serum acetylcholinesterase (AChE) activity and impaired neuromuscular coordination and spatial memory compared to control rats. Copper-intoxicated rats showed significant increase in liver and hippocampus copper content (99.1 and 73% increase, respectively), 40.7% reduction in hepatic zinc content, and interestingly, 77.1% increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats. Massive grade 4 copper depositions and grade 1 copper-associated protein in hepatocytes of copper-intoxicated rats were substantiated by rhodanine and orcein stains, respectively. Copper-intoxicated rats demonstrated swelling and increase in the number of astrocytes and copper deposition in the choroid plexus, with degenerated neurons showing pyknotic nuclei and dense eosinophilic cytoplasm. In conclusion, the present study shows the first evidence in vivo that chronic copper toxicity causes impaired spatial memory and neuromuscular coordination, swelling of astrocytes, decreased serum AChE activity, copper deposition in the choroid plexus, neuronal degeneration, and augmented levels of copper and zinc in the hippocampus of male Wistar rats.

Chronic copper intoxication causes impaired spatial memory and hippocampus copper elevation in wistar rats

Background: Animal models of copper toxicities rarely exhibit neurological impairments and increased brain copper accumulation impeding the development of novel therapeutic approaches to treat neurodegenerative diseases having high brain Cu content. Aims: The aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g b.w.) daily for 90 days on copper and zinc levels in liver, kidney and hippocampus; expression of hepatic metallothionein-I and Atp7b gene, with metallothionein-III and acetylcholine esterase (AChE) gene in brain, biochemical parameters and neurobehavioral functions (by Morris water maze) of male wistar rats. Results: Copper administered animals exhibited significantly decreased serum AChE activity, increased hepatic metallothionein-I gene expression, impaired neuromuscular coordination and spatial memory compared to control rats. Copper intoxicated rats showed significant increase in liver, hippocampus and kidney tissues copper content (99.1, 73 and 74.9 % increase respectively), 40.7 % reduction in hepatic zinc content and interestingly, 77.1% increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats. Massive copper deposition and copper associated protein in hepatocytes of copper intoxicated rats was substantiated by rhodanine and orcein stains respectively. Copper intoxicated rats demonstrated swelling and increase in number of astrocytes, degenerated neurons having pyknotic nuclei with copper deposition in choroid plexus. Conclusion: Present study shows the first evidence in vivo that chronic copper toxicity causes impaired spatial memory, swelling of astrocytes, decreased serum AChE activity,

Rotenone induced neurotoxicity in rat brain areas: A histopathological study

Rotenone a pesticide is known to induce neurotoxicity. In earlier study we correlated rotenone induced biochemical changes and cerebral damage in brain areas with neuromuscular coordination in rats. The present study involves investigation of rotenone induced histopathological changes in the brain areas, viz. striatum (STR) and substantia nigra (SN) using HE (hematoxylin and eosin) and CV (Cresyl Violet) staining after 1, 7, and 14 day of unilateral intranigral administration of rotenone (3, 6 and 12μg/5μl) in adult male SD rats. Significant morphological changes in cell area or shape were shown by HE staining. The neuronal degeneration was shown by distorted neuronal cells, shrinkage of nuclei, dark staining in the regions of rotenone treated animals by CV staining. Rota rod test demonstrated significant impairment in motor coordination after 14days of treatment along with decreased GSH and increased MDA in STR and mid brain (MB). The study inferred rotenone causes neuronal damage which is evident by histopathological changes, impaired neuromuscular coordination and biochemical changes. The pattern of histopathological alterations corresponds with behavioral and biochemical manifestations.

A study to correlate rotenone induced biochemical changes and cerebral damage in brain areas with neuromuscular coordination in rats

Rotenone induces neurotoxicity but its correlation with biochemical and cerebral changes in rat brain regions are not well defined. In the present study rotenone was administered (3, 6 and12 μg/μl) intranigrally in adult male SD rats and its effect was assessed on neuromuscular coordination and in different brain areas viz. striatum (STR), mid-brain (MB), frontal cortex (FC) and hippocampus (HP) cerebral and biochemical changes on 1st and 7th day after treatment. All the doses of rotenone significantly impaired neuromuscular coordination performance on Rota rod test on 1st and 7th day. TTC staining showed significant increase in cerebral injury volume on 1st and 7th day after rotenone treatment indicating mitochondrial enzyme deficiency but increase after 7th day was less that after 1st day. Rotenone treated rats showed significant decrease in GSH and increase in MDA in different brain regions though the pattern was varied. After 1 day of rotenone (6 and 12 μg) treatment significant decrease in GSH was observed in STR and MB while MDA was significantly increased only in MB. The maximal effect on GSH and MDA was obtained in STR and MB on 7th day after treatment with 12 μg dose of rotenone. Thus, based on the occurrence of changes, it may be suggested that impairment of neuromuscular coordination is inked to oxidative stress rather than mitochondrial enzyme deficiency, all the processes are correlated with each other with the progression of time. MB appeared as most sensitive brain area towards rotenone toxicity.

Cycling impairs neuromuscular control during running in triathletes: Implications for performance, injury and intervention

Triathletes report incoordination when running after cycling. Fatigue is likely to contribute but impaired coordination of running may also relate to interference with neuromuscular control independent of fatigue. We investigated (a) the influence of the bike-run transition on neuromuscular coordination of running (i.e. does cycling have a direct effect on running?), (b) the effect of altered neuromuscular coordination on run-economy (RE, steady-state V02), (c) the association between exercise-related-leg-pain (ERLP) and neuromuscular coordination of running, (d) the role of fatigue in coordination changes, and (e) the effectiveness of taping as an intervention for impaired neuromuscular coordination. 34 highly trained triathletes participated. Three-dimensional kinematics, muscle recruitment and RE were compared between a control-run (no prior exercise) and a 30-min transition-run (preceded by 20 min of moderate-intensity cycling; i.e. run vs. cycle-run). Fatigue was evaluated using an established isometric protocol. Neuromuscular coordination was compared between transition-runs with and without augmented-low-Dye anti-pronation-taping applied. Short periods of cycling had no direct effect on running kinematics or muscle activity in most (−70%) highly trained triathletes. However, running muscle activity was influenced by cycling in a proportion (−30%) of highly trained triathletes (70.1 ± 13.7% change in mean EMG amplitude). This influence was not related to altered kinematics or fatigue, but instead was a direct effect of cycling on motor commands for running. This altered muscle recruitment was associated with reduced RE (3.7 ± 0.9% increase in V02) and 2.5-times greater likelihood of a history of ERLP, but was improved by an established taping intervention (70.5 ± 18.6% reversal of altered muscle recruitment).