Assessment of Motor Units in Neuromuscular Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Henderson RD
PROVIDER: S-EPMC5233620 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Publications
Assessment of Motor Units in Neuromuscular Disease.
Henderson Robert D RD McCombe Pamela A PA
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20170101 1
The motor unit comprises the anterior horn cell, its axon, and the muscle fibers that it innervates. Although the true number of motor units is unknown, the number of motor units appears to vary greatly between different muscles and between different individuals. Assessment of the number and function of motor units is needed in diseases of the anterior horn cell and other motor nerve disorders. Amyotrophic lateral sclerosis is the most important disease of anterior horn cells. The need for an ef ...[more]
Similar Datasets
Project description:A complex and functional living cellular system requires the interaction of one or more cell types to perform specific tasks, such as sensing, processing, or force production. Modular and flexible platforms for fabrication of such multi-cellular modules and their characterization have been lacking. Here, we present a modular cellular system, made up of multi-layered tissue rings containing integrated skeletal muscle and motor neurons (MNs) embedded in an extracellular matrix. The MNs were differentiated from mouse embryonic stem cells through the formation of embryoid bodies (EBs), which are spherical aggregations of cells grown in a suspension culture. The EBs were integrated into a tissue ring with skeletal muscle, which was differentiated in parallel, to create a co-culture amenable to both cell types. The multi-layered rings were then sequentially placed on a stationary three-dimensional-printed hydrogel structure resembling an anatomical muscle-tendon-bone organization. We demonstrate that the site-specific innervation of a group of muscle fibers in the multi-layered tissue rings allows for muscle contraction via chemical stimulation of MNs with glutamate, a major excitatory neurotransmitter in the mammalian nervous system, with the frequency of contraction increasing with glutamate concentration. The addition of tubocurarine chloride (a nicotinic receptor antagonist) halted the contractions, indicating that muscle contraction was MN induced. With a bio-fabricated system permitting controllable mechanical and geometric attributes in a range of length scales, our novel engineered cellular system can be utilized for easier integration of other modular "building blocks" in living cellular and biological machines.
| S-EPMC6444989 | biostudies-literature
Project description:Neuromuscular blocking agents can be used for purposes such as eliminating ventilator-patient dyssynchrony, facilitating gas exchange by reducing intra-abdominal pressure and improving chest wall compliance, reducing risk of lung barotrauma, decreasing contribution of muscles to oxygen consumption by preventing shivering and limiting elevations in intracranial pressure caused by airway stimulation in patients supported with mechanical ventilation in intensive care units. Adult Respiratory Distress Syndrome (ARDS), status asthmaticus, increased intracranial pressure and therapeutic hypothermia following ventricular fibrillation-associated cardiac arrest are some of clinical conditions that can be sustained by neuromuscular blockade. Appropriate indication and clinical practice have gained importance considering side effects such as ICU-acquired weakness, masking seizure activity and longer durations of hospital and ICU stays. We mainly aimed to review the current literature regarding neuromuscular blockade in up-to-date clinical conditions such as improving oxygenation in early ARDS and preventing shivering in the therapeutic hypothermia along with summarising the clinical practice in adult ICU in this report.
| S-EPMC6645848 | biostudies-literature
Project description:BackgroundA substantial impediment to progress in trials of new therapies in neuromuscular disorders is the absence of responsive outcome measures that correlate with patient functional deficits and are sensitive to early disease processes. Irrespective of the primary molecular defect, neuromuscular disorder pathological processes include disturbance of intramuscular water distribution followed by intramuscular fat accumulation, both quantifiable by MRI. In pathologically distinct neuromuscular disorders, we aimed to determine the comparative responsiveness of MRI outcome measures over 1 year, the validity of MRI outcome measures by cross-sectional correlation against functionally relevant clinical measures, and the sensitivity of specific MRI indices to early muscle water changes before intramuscular fat accumulation beyond the healthy control range.MethodsWe did a prospective observational cohort study of patients with either Charcot-Marie-Tooth disease 1A or inclusion body myositis who were attending the inherited neuropathy or muscle clinics at the Medical Research Council (MRC) Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK. Genetic confirmation of the chromosome 17p11.2 duplication was required for Charcot-Marie-Tooth disease 1A, and classification as pathologically or clinically definite by MRC criteria was required for inclusion body myositis. Exclusion criteria were concomitant diseases and safety-related MRI contraindications. Healthy age-matched and sex-matched controls were also recruited. Assessments were done at baseline and 1 year. The MRI outcomes-fat fraction, transverse relaxation time (T2), and magnetisation transfer ratio (MTR)-were analysed during the 12-month follow-up, by measuring correlation with functionally relevant clinical measures, and for T2 and MTR, sensitivity in muscles with fat fraction less than the 95th percentile of the control group.FindingsBetween Jan 19, 2010, and July 7, 2011, we recruited 20 patients with Charcot-Marie-Tooth disease 1A, 20 patients with inclusion body myositis, and 29 healthy controls (allocated to one or both of the 20-participant matched-control subgroups). Whole muscle fat fraction increased significantly during the 12-month follow-up at calf level (mean absolute change 1.2%, 95% CI 0.5-1.9, p=0.002) but not thigh level (0.2%, -0.2 to 0.6, p=0.38) in patients with Charcot-Marie-Tooth disease 1A, and at calf level (2.6%, 1.3-4.0, p=0.002) and thigh level (3.3%, 1.8-4.9, p=0.0007) in patients with inclusion body myositis. Fat fraction correlated with the lower limb components of the inclusion body myositis functional rating score (?=-0.64, p=0.002) and the Charcot-Marie-Tooth examination score (?=0.63, p=0.003). Longitudinal T2 and MTR changed consistently with fat fraction but more variably. In muscles with a fat fraction lower than the control group 95th percentile, T2 was increased in patients compared with controls (regression coefficients: inclusion body myositis thigh 4.0 ms [SE 0.5], calf 3.5 ms [0.6]; Charcot-Marie-Tooth 1A thigh 1.0 ms [0.3], calf 2.0 ms [0.3]) and MTR reduced compared with controls (inclusion body myositis thigh -1.5 percentage units [pu; 0.2], calf -1.1 pu [0.2]; Charcot-Marie-Tooth 1A thigh -0.3 pu [0.1], calf -0.7 pu [0.1]).InterpretationMRI outcome measures can monitor intramuscular fat accumulation with high responsiveness, show validity by correlation with conventional functional measures, and detect muscle water changes preceding marked intramuscular fat accumulation. Confirmation of our results in further cohorts with these and other muscle-wasting disorders would suggest that MRI biomarkers might prove valuable in experimental trials.FundingMedical Research Council UK.
| S-EPMC4672173 | biostudies-literature
Project description:BackgroundSarcopenia can be associated with the disease etiologies other than degenerative processes, such as neurologic disease including cerebral palsy, myelomeningocele, or Duchenne muscular dystrophy, even in children. Although the relationship between neurologic disease and scoliosis or ambulatory function is known, the mediators affecting scoliosis or gait function in these patients are unclear, an example might be sarcopenia. This study aimed to assess the degree of sarcopenia in young patients with neurologic diseases using computed tomography (CT), and analyze the correlation between sarcopenia and scoliosis or ambulatory function.MethodsPediatric and young adult patients (≤ 25 years old) who underwent whole-spine or lower-extremity CT were retrospectively included. From bilateral psoas muscle areas (PMAs) at the L3 level, the psoas muscle z-score (PMz) and psoas muscle index [PMI = PMA/(L3 height)²] were calculated. The t-test, Fisher's exact test, and logistic regression analyses were performed.ResultsA total of 121 patients (56 men, mean age 12.2 ± 3.7 years) were included with 79 neurologic and 42 non-neurologic diseases. Patients with neurologic diseases had lower PMz (P = 0.013) and PMI (P = 0.026) than patients without. In neurologic disease patients, severe scoliosis patients showed lower PMz (P < 0.001) and PMI (P = 0.001). Non-ambulatory patients (n = 42) showed lower BMI (β = 0.727, P < 0.001) and PMz (β = 0.547, P = 0.025). In non-ambulatory patients, patients with severe scoliosis also showed lower PMz (P < 0.001) and PMI (P = 0.004).ConclusionPatients with neurologic diseases could have sarcopenia even in young age. Psoas muscle volume was also associated with ambulatory function in these patients. Sarcopenia was more severe in severe scoliosis patients in the non-ambulatory subgroup.
| S-EPMC10226852 | biostudies-literature
Project description:OBJECTIVE:To determine the size, shape and distribution of single human motor units in-vivo in healthy controls of different ages. METHODS:A novel diffusion-weighted magnetic resonance imaging (MRI) technique was used in combination with in-scanner electrical stimulation to quantify the shape, cross-sectional area, and dimensions of individual motor units in 10 healthy subjects. RESULTS:Thirty-one discrete motor units were studied. The majority were elliptical or crescent shaped, but occasional split motor units were observed. The mean motor unit cross sectional area was 26.7 ± 11.2 mm2, the mean maximum dimension was 10.7 ± 3.3 mm, and the mean minimum dimension was 4.5 ± 1.2 mm. Subjects aged over 40 had significantly larger maximum dimensions than those below this age (p < 0.05). CONCLUSIONS:Motor unit MRI (MUMRI) is a novel technique capable of revealing the size, shape and position of multiple motor units in human muscles. It is reproducible, non-invasive, and sufficiently sensitive to detect physiologically relevant changes in motor unit morphology with age. SIGNIFICANCE:To our knowledge, these results provide the first imaging assessment of human motor unit morphology. The technique shows promise both as a diagnostic tool and as a biomarker in longitudinal studies of disease progression.
| S-EPMC7208543 | biostudies-literature
Project description:Little is known about the respiratory-related discharge properties of motor units driving any of the eight muscles that control the movement, shape, and stiffness of the mammalian tongue.To characterize the respiratory-related discharge of genioglossus motor units as synaptic drive to the hypoglossal motoneuron pool is increased with hypercapnia.We recorded airflow, genioglossus muscle EMG activity, and the respiratory-related discharge of 30 genioglossus muscle motor units in spontaneously breathing, urethane-anesthetized rats under control conditions and in hypercapnia (inspired CO2: 3, 6, 9, and 12%, 3-5 min at each level).All motor units were active throughout all or most of inspiration. Nine of 30 units showed "preinspiratory" activity (discharge onset within the last 20% of expiration), with continued discharge into inspiration. Six inspiratory units transitioned to a preinspiratory pattern when inspired CO2 exceeded 6%. For the majority of units (23/30), discharge rate increased with hypercapnia, with the maximum increase averaging about 50%. The average variability of interspike intervals within a spike train increased from 33% under baseline conditions to 50% with maximal hypercapnia.(1) The discharge pattern of genioglossus muscle motor units can be altered by hypercapnia; (2) most, but not all, genioglossus motor units receive synaptic input from CO2-sensitive chemoreceptors; (3) individual motor units have a wide range of CO2 sensitivities; and (4) hypercapnia significantly increases the variability of motor unit discharge, which may enhance muscle force output.
| S-EPMC2718418 | biostudies-other
Project description:The genioglossus is a major upper airway dilator muscle thought to be important in obstructive sleep apnea pathogenesis. Aging is a risk factor for obstructive sleep apnea although the mechanisms are unclear and the effects of aging on motor unit remodeled in the genioglossus remains unknown. To assess possible changes associated with aging we compared quantitative parameters related to motor unit potential morphology derived from EMG signals in a sample of older (n?=?11; >55 years) versus younger (n?=?29; <55 years) adults. All data were recorded during quiet breathing with the subjects awake. Diagnostic sleep studies (Apnea Hypopnea Index) confirmed the presence or absence of obstructive sleep apnea. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which estimated a MUP template from each extracted motor unit potential train (MUPT) for both the selective concentric needle and concentric needle macro (CNMACRO) recorded EMG signals. 2074 MUPTs from 40 subjects (mean±95% CI; older AHI 19.6±9.9 events/hr versus younger AHI 30.1±6.1 events/hr) were extracted. MUPs detected in older adults were 32% longer in duration (14.7±0.5 ms versus 11.1±0.2 ms; P ?=? 0.05), with similar amplitudes (395.2±25.1 µV versus 394.6±13.7 µV). Amplitudes of CNMACRO MUPs detected in older adults were larger by 22% (62.7±6.5 µV versus 51.3±3.0 µV; P<0.05), with areas 24% larger (160.6±18.6 µV.ms versus 130.0±7.4 µV.ms; P<0.05) than those detected in younger adults. These results confirm that remodeled motor units are present in the genioglossus muscle of individuals above 55 years, which may have implications for OSA pathogenesis and aging related upper airway collapsibility.
| S-EPMC4128697 | biostudies-literature
Project description:Spinal muscular atrophy (SMA), a recessive genetic disease, affects lower motoneurons leading to denervation, atrophy, paralysis and in severe cases death. Reduced levels of survival motor neuron (SMN) protein cause SMA. As a first step towards generating a genetic model of SMA in zebrafish, we identified three smn mutations. Two of these alleles, smnY262stop and smnL265stop, were stop mutations that resulted in exon 7 truncation, whereas the third, smnG264D, was a missense mutation corresponding to an amino acid altered in human SMA patients. Smn protein levels were low/undetectable in homozygous mutants consistent with unstable protein products. Homozygous mutants from all three alleles were smaller and survived on the basis of maternal Smn dying during the second week of larval development. Analysis of the neuromuscular system in these mutants revealed a decrease in the synaptic vesicle protein, SV2. However, two other synaptic vesicle proteins, synaptotagmin and synaptophysin were unaffected. To address whether the SV2 decrease was due specifically to Smn in motoneurons, we tested whether expressing human SMN protein exclusively in motoneurons in smn mutants could rescue the phenotype. For this, we generated a transgenic zebrafish line with human SMN driven by the motoneuron-specific zebrafish hb9 promoter and then generated smn mutant lines carrying this transgene. We found that introducing human SMN specifically into motoneurons rescued the SV2 decrease observed in smn mutants. Our analysis indicates the requirement for Smn in motoneurons to maintain SV2 in presynaptic terminals indicating that Smn, either directly or indirectly, plays a role in presynaptic integrity.
| S-EPMC2742401 | biostudies-literature
Project description:BACKGROUND:Phase synchrony has extensively been studied for understanding neural coordination in health and disease. There are a few studies concerning the implications in the context of BCIs, but its potential for establishing a communication channel in patients suffering from neuromuscular disorders remains totally unexplored. We investigate, here, this possibility by estimating the time-resolved phase connectivity patterns induced during a motor imagery (MI) task and adopting a supervised learning scheme to recover the subject's intention from the streaming data. METHODS:Electroencephalographic activity from six patients suffering from neuromuscular disease (NMD) and six healthy individuals was recorded during two randomly alternating, externally cued, MI tasks (clenching either left or right fist) and a rest condition. The metric of Phase locking value (PLV) was used to describe the functional coupling between all recording sites. The functional connectivity patterns and the associate network organization was first compared between the two cohorts. Next, working at the level of individual patients, we trained support vector machines (SVMs) to discriminate between "left" and "right" based on different instantiations of connectivity patterns (depending on the encountered brain rhythm and the temporal interval). Finally, we designed and realized a novel brain decoding scheme that could interpret the intention from streaming connectivity patterns, based on an ensemble of SVMs. RESULTS:The group-level analysis revealed increased phase synchrony and richer network organization in patients. This trend was also seen in the performance of the employed classifiers. Time-resolved connectivity led to superior performance, with distinct SVMs acting as local experts, specialized in the patterning emerged within specific temporal windows (defined with respect to the external trigger). This empirical finding was further exploited in implementing a decoding scheme that can be activated without the need of the precise timing of a trigger. CONCLUSION:The increased phase synchrony in NMD patients can turn to a valuable tool for MI decoding. Considering the fast implementation for the PLV pattern computation in multichannel signals, we can envision the development of efficient personalized BCI systems in assistance of these patients.
| S-EPMC6206934 | biostudies-literature
Project description:BACKGROUND:Clinical phenotypic heterogeneity represents a major barrier to trials in motor neuron disease (MND) and objective surrogate outcome measures are required, especially for slowly progressive patients. We assessed responsiveness of clinical, electrophysiological and radiological muscle-based assessments to detect MND-related progression. MATERIALS AND METHODS:A prospective, longitudinal cohort study of 29 MND patients and 22 healthy controls was performed. Clinical measures, electrophysiological motor unit number index/size (MUNIX/MUSIX) and relative T2- and diffusion-weighted whole-body muscle magnetic resonance (MR) were assessed three times over 12 months. Multi-variable regression models assessed between-group differences, clinico-electrophysiological associations, and longitudinal changes. Standardized response means (SRMs) assessed sensitivity to change over 12 months. RESULTS:MND patients exhibited 18% higher whole-body mean muscle relative T2-signal than controls (95% CI 7-29%, p?<?0.01), maximal in leg muscles (left tibialis anterior 71% (95% CI 33-122%, p?<?0.01). Clinical and electrophysiological associations were evident. By 12 months, 16 patients had died or could not continue. In the remainder, relative T2-signal increased over 12 months by 14-29% in right tibialis anterior, right quadriceps, bilateral hamstrings and gastrocnemius/soleus (p?<?0.01), independent of onset-site, and paralleled progressive weakness and electrophysiological loss of motor units. Highest clinical, electrophysiological and radiological SRMs were found for revised ALS-functional rating scale scores (1.22), tibialis anterior MUNIX (1.59), and relative T2-weighted leg muscle MR (right hamstrings: 0.98), respectively. Diffusion MR detected minimal changes. CONCLUSION:MUNIX and relative T2-weighted MR represent objective surrogate markers of progressive denervation in MND. Radiological changes were maximal in leg muscles, irrespective of clinical onset-site.
| S-EPMC6954906 | biostudies-literature