The dystrophinopathies in Costa Rica

A five-years long study aiming to describe the basic genetic epidemiology of the dystrophinopathies in Costa Rica recruited 31 patients with clinical symptoms of DMD/BMD at the National Children's Hospital (HNN). This center is the obligate reference hospital of the national health system for genetic diseases, however, the geographic origin of the patients, a low percentage of deletions and a high proportion of de novo mutations found among them indicate that a significant ascertainment bias impedes a substantial scientific approach to confront and alleviate the problems posed by these severe diseases in Costa Rica.     

Motor unit tracking with high-density surface EMG

Following (tracking) individual motor units over time can provide important new insights, both into the relationships among various motor unit (MU) morphological and functional properties and into how these properties are influenced by neuromuscular disorders or interventions. The present study aimed to determine whether high-density surface EMG (HD-sEMG) recordings, which use an array of surface electrodes over a muscle, can increase the yield of MU tracking studies in terms of the number of MUs that can be tracked. For that purpose, four HD-sEMG recording sessions were performed on the thenar muscles of ten healthy subjects. Decomposition of the recorded composite responses yielded a study total of 2849 motor unit action potentials (MUAPs). MUAPs that were found in both of the first two sessions, performed on the same day, were defined as trackable MUAPs. Our results show that 22 (median value; range, 13–34) MUAPs per nerve were trackable, which represented approximately 5% of the total MU population. Of these trackable MUAPs, 16 (11–26) could also be found in one or both of the third and fourth sessions, which were performed between 1 and 13 weeks after the initial studies. Nine (4–18) MUAPs were found in all four sessions. Many of the characteristic MUAP shapes matched well between sessions, even when these sessions were several weeks apart. However, some MUAPs seem very sensitive to changes in arm position or in the muscle’s morphology (e.g., to changes in muscle fiber length due to variable degrees of thumb flexion or extension), particularly those from larger and/or superficial MUs. Standardization is, therefore, essential to detect even small MUAP changes, as may occur with pathology or interventions. If this is accomplished, MU tracking with HD-sEMG may prove to be a powerful tool for a promising type of neurophysiological investigation.     

Motor evoked potentials with magnetic stimulation: correlations with height

The relationship between height and motor evoked potentials (MEPs) was studied in 52 healthy young subjects. Evoked responses from the abductor digiti minimi and tibialis anterior muscles were obtained following magnetic stimulation over the vertex and the cervical and lumbar regions. The latencies of MEPs were highly correlated with height. The conduction time from the motor cortex to the lumbar region was also correlated with height, but that from the motor cortex to the cervical region was not. It is concluded that height is an important variable in defining the MEP normality.     

Motor unit abnormalities in Dystonia musculorum mice

Dystonia musculorum (dt) is a mouse inherited sensory neuropathy caused by mutations in the dystonin gene. While the primary pathology lies in the sensory neurons of dt mice, the overt movement disorder suggests motor neurons may also be affected. Here, we report on the contribution of motor neurons to the pathology in dt(27J) mice. Phenotypic dt(27J) mice display reduced alpha motor neuron cell number and eccentric alpha motor nuclei in the ventral horn of the lumbar L1 spinal cord region. A dramatic reduction in the total number of motor axons in the ventral root of postnatal day 15 dt(27J) mice was also evident. Moreover, analysis of the trigeminal nerve of the brainstem showed a 2.4 fold increase in number of degenerating neurons coupled with a decrease in motor neuron number relative to wild type. Aberrant phosphorylation of neurofilaments in the perikaryon region and axonal swellings within the pre-synaptic terminal region of motor neurons were observed. Furthermore, neuromuscular junction staining of dt(27J) mouse extensor digitorum longus and tibialis anterior muscle fibers showed immature endplates and a significant decrease in axon branching compared to wild type littermates. Muscle atrophy was also observed in dt(27J) muscle. Ultrastructure analysis revealed amyelinated motor axons in the ventral root of the spinal nerve, suggesting a possible defect in Schwann cells. Finally, behavioral analysis identified defective motor function in dt(27J) mice. This study reveals neuromuscular defects that likely contribute to the dt(27J) pathology and identifies a critical role for dystonin outside of sensory neurons.     

Motor unit behavior during clonus.

Medial gastrocnemius surface electromyographic activity and intramuscular electromyographic activity were recorded from six individuals with chronic cervical spinal cord injury to document the recruitment order of motor units during clonus. Four subjects induced clonus that lasted up to 30 s while two subjects induced clonus that they actively stopped after 1 min. Mean clonus frequency in different subjects ranged from 4.7 to 7.0 Hz. Most of the 166 motor units recorded during clonus (98%) fired once during each contraction but at slightly different times during each cycle. Other motor units fired during some clonus cycles (1%) or in bursts (1%). When 59 pairs of units were monitored over consecutive clonus cycles (n = 5-89 cycles), only 8 pairs of units altered their recruitment order in some cycles. Recruitment reversals only occurred in units that fired close together in the clonus cycle. These data demonstrate that orderly motor unit recruitment occurs during involuntary contractions of muscles paralyzed chronically by cervical spinal cord injury, providing further support for the importance of spinal mechanisms in the control of human motor unit behavior.     

Motor unit number estimation--a Bayesian approach

All muscle contractions are dependent on the functioning of motor units. In diseases such as amyotrophic lateral sclerosis (ALS), progressive loss of motor units leads to gradual paralysis. A major difficulty in the search for a treatment for these diseases has been the lack of a reliable measure of disease progression. One possible measure would be an estimate of the number of surviving motor units. Despite over 30 years of motor unit number estimation (MUNE), all proposed methods have been met with practical and theoretical objections. Our aim is to develop a method of MUNE that overcomes these objections. We record the compound muscle action potential (CMAP) from a selected muscle in response to a graded electrical stimulation applied to the nerve. As the stimulus increases, the threshold of each motor unit is exceeded, and the size of the CMAP increases until a maximum response is obtained. However, the threshold potential required to excite an axon is not a precise value but fluctuates over a small range leading to probabilistic activation of motor units in response to a given stimulus. When the threshold ranges of motor units overlap, there may be alternation where the number of motor units that fire in response to the stimulus is variable. This means that increments in the value of the CMAP correspond to the firing of different combinations of motor units. At a fixed stimulus, variability in the CMAP, measured as variance, can be used to conduct MUNE using the "statistical" or the "Poisson" method. However, this method relies on the assumptions that the numbers of motor units that are firing probabilistically have the Poisson distribution and that all single motor unit action potentials (MUAP) have a fixed and identical size. These assumptions are not necessarily correct. We propose to develop a Bayesian statistical methodology to analyze electrophysiological data to provide an estimate of motor unit numbers. Our method of MUNE incorporates the variability of the threshold, the variability between and within single MUAPs, and baseline variability. Our model not only gives the most probable number of motor units but also provides information about both the population of units and individual units. We use Markov chain Monte Carlo to obtain information about the characteristics of individual motor units and about the population of motor units and the Bayesian information criterion for MUNE. We test our method of MUNE on three subjects. Our method provides a reproducible estimate for a patient with stable but severe ALS. In a serial study, we demonstrate a decline in the number of motor unit numbers with a patient with rapidly advancing disease. Finally, with our last patient, we show that our method has the capacity to estimate a larger number of motor units.     

Motor potentials evoked by paired cortical stimuli

We recorded the motor evoked potentials (MEPs) from the abductor pollicis brevis muscle, after supramaximal electrical transcranial stimulation, and studied the effect of paired transcranial shocks with varying interstimulus time intervals, in 10 normal subjects, 4 patients with median nerve neuropathy and 2 patients with motoneurone disease.In relaxed muscles the amplitude of the MEP evoked by a single shock averaged 30% of the M wave. With intervals from 1 to 2.5 msec 2 shocks evoked one MEP far larger in size than the control MEP (70% of the M wave). With intervals of 10 msec and longer, the 2 shocks evoked 2 independent MEPs; the size of the MEP following the second shock (test) was inversely correlated with the size of the control MEP: the more the control MEP approached the size of the M wave, the smaller the test MEP. Single motor unit records showed that, in the normal subjects and patients with peripheral neuropathy, the same motor unit was activated either by the first or the second shock, whereas in the patients with motoneurone disease it fired twice. In active muscles, the control MEP averaged 70% of the M wave. With intervals of 10 msec and longer the test MEP was markedly suppressed; with 100 msec intervals it fully recovered. In relaxed muscles, by delivering a double shock at a 1.5 msec interval, thus evoking a large MEP, followed by a second double-shock, the test MEP was completely suppressed for a period of 20 msec; it began to recover at 50 msec intervals and fully recovered after 150 msec.These results indicate that: (1) high-threshold spinal motoneurones can profit from temporal summation if double-shocks are delivered at short time intervals; (2) the synchronous excitation of the motoneuronal pool produced by transcranial stimulation is followed by a 20 msec period of absolute inhibition, possibly through a massive activation of the Renshaw system; (3) during voluntary contraction, only a portion of the motoneuronal pool remains refractory, possibly because of the enhanced spinal excitability.     

Motor unit recruitment during prolonged isometric contractions

Motor unit recruitment patterns were studied during prolonged isometric contraction using fine wire electrodes. Single motor unit potentials were recorded from the brachial biceps muscle of eight male subjects, during isometric endurance experiments conducted at relative workloads corresponding to 10% and 40% of maximal voluntary contraction (MVC), respectively. The recordings from the 10% MVC experiment demonstrated a characteristic time-dependent recruitment. As the contraction progressed both the mean number of motor unit spikes counted and the mean amplitude of the spikes increased significantly (P<0.01). This progressive increase in spike activity was the result of a discontinuous process with periods of increasing and decreasing activity. The phenomenon in which newly recruited motor units replace previously active units is termed motor unit rotation and appeared to be an important characteristic of motor control during a prolonged low level contraction. In contrast to the 10% MVC experiment, there was no indication of de novo recruitment in the 40% MVC experiment. Near the point of exhaustion a marked change in action potential shape and duration dominated the recordings. These findings demonstrate a conspicuous difference in the patterns of motor unit recruitment during a 10% and a 40% MVC sustained contraction. It is suggested that there is a close relationship between intrinsic muscle properties and central nervous system recruitment strategies which is entirely different in fatiguing high and low level isometric contractions.     

Evoked potentials and unit activity in the cat somatosensory cortex

Investigation of unit activity of the cat somatosensory cortex has shown that the principal role in the genesis of the primary response, the response to stimulation of the thalamic relay nucleus, the callosal response, and certain other forms of evoked potentials (EPs) of the somatosensory cortex is played by neurons not usually responding by spike generation during EP development. The EPs reflect what the cortical neurons received from the afferent volley, and the level of their polarization, but they are not a reliable indicator of fast nervous processes in the cerebral cortex. The EPs reflect postsynaptic potentials (PSPs) of neurons not directly participating actively in the analysis of information reaching the cortex.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No, 4, pp. 360–367, July–August, 1970.     

Exploring the Split-Hand Phenomenon in ALS with Motor unit Number Index (MUNIX)

Human Physiology - Split-hand phenomenon in amyotrophic lateral sclerosis (ALS) is characterized by uneven progression of muscle weakness in the intrinsic hand muscles, with predominant wasting of...     

Motor unit discharge pattern and conduction velocity in patients with upper motor neuron syndrome

Motor unit properties were analyzed in patients with upper motor neuron syndrome (UMNS). Multi-channel surface electromyographic (EMG) signals were recorded for 300 s from the biceps brachii muscle of seven male subacute patients (time from lesion, mean ± SE, 4.9 ± 1.0 months). In three patients, both arms were investigated, leading to 10 recorded muscles. Patients were analyzed in rest-like condition with motor units activated due to pathological muscle overactivity. For a total of 12 motor units, the complete discharge pattern was extracted from EMG decomposition. Interpulse interval variability was 7.8 ± 0.9%. At minimum discharge rate (6.4 ± 0.4 pulses per second, pps), conduction velocity was smaller than at maximum discharge rate (12.0 ± 0.9 pps) in all motor units (3.60 ± 0.21 m/s vs. 3.84 ± 0.20 m/s). Conduction velocity changed by 1.35 ± 0.48% (different from zero, P < 0.01) for each increase of 1 pps in discharge rate. It was concluded that conduction velocity of low-threshold motor units in subacute patients with UMNS had similar values as reported in healthy subjects and was positively correlated to instantaneous discharge rate (velocity recovery function of muscle fibers).     

Motor unit acceleration maps and interference mechanomyographic distribution

The study analyses the two-dimensional distribution of surface mechanomyographic (MMG) signal generated by the activation of single motor units located in three transverse positions in the tibialis anterior muscle. In 12 healthy volunteers, surface MMG signals were recorded from the tibialis anterior muscle with a 3x4 grid of accelerometers spaced by 20 and 30mm in the transverse and longitudinal direction. Three intramuscular electromyographic (EMG) signals were recorded with wire electrodes inserted 20-mm apart, between the first and second most proximal accelerometers of each column of the grid. The subject was asked to activate three different motor units (target motor units) in three contractions with visual feedback from each of the three intramuscular recordings (three locations). The MMG signals from the 12 accelerometers were averaged using the intramuscular single motor unit action potentials as trigger in order to obtain surface motor unit acceleration maps (MUAMs). The peak-to-peak value of the averaged MMG depended on motor unit location (P<0.001) and on the transverse position of the accelerometer in the grid (P<0.05). Moreover, MUAM amplitude depended on the interaction between motor unit location and transverse accelerometer position (P<0.05), demonstrating an influence of motor unit location on the generated MUAM. The observed dependency of MUAMs on motor unit location provides a quantitative analysis of the effect of the volume conductor on the recorded surface MMG signal.     

Motor unit activity during long-lasting intermittent muscle contractions in humans

Changes accompanying long-lasting intermittent muscle contractions (30%–50% of the maximal) were investigated by tracing the activity of 38 motor units (MU) of the human biceps brachii muscle recorded from fine-wire branched electrodes. The motor task was a continuous repetition of ramp-and-hold cycles of isometric flexion contractions. During ramp-up phases a significant decline in recruitment thresholds was found with no changes in the discharge pattern. During ramp-down phases the unchanged mean value of derecruitment thresholds during the task was accompanied by increased duration of the last two interspike intervals (ISI). These findings would suggest that during fatigue development the main compensatory mechanism during ramp-up contractions is space coding while for ramp-down contractions it is rate coding. During the steady-state phases the mean value of ISI, as well as the firing variability, had increased by the end of the task in most of the MU investigated . In addition 17 recruited MU were also investigated. These units revealed a lower initial discharge rate and a faster decrease in the mean discharge rate with the development of fatigue. The gradual reduction of the recruitment threshold of already active MU and the recruitment of new units demonstrated an increased excitability of the motorneuron pool during fatigue. A typical recruitment pattern (a first short ISI followed by a long one) was observed during ramp-up contractions in units active from the very beginning of the task, as well as during sustained contractions at the onset of the stable discharge of the additionally recruited MU. Accepted: 23 September 1997     

Single motor unit and fiber action potentials during fatigue

Muscle fatigue is defined as a loss of tension development during constant stimulation. Although the relationship is not well documented, muscle fatigue has been inferred from electromyogram (EMG) signals. The purpose of this study was to determine the relationship between the amplitude and duration of single motor unit action potentials (MUAPs) and the loss of tension development (fatigue) in the medial gastrocnemius muscles of cats. Single motor units were fatigued by continuous stimulation at 10 or 80 Hz or with trains of 40-Hz stimuli. When motor units were stimulated at 10 Hz and with trains at 40 Hz (low frequency), tension declined and remained depressed during recovery. The changes in the MUAP correlated poorly with changes in tension. During and after stimulation at 80 Hz (high frequency), changes in the amplitude and duration of MUAPs correlated highly with changes in tension development. Since the EMG signal is dependent on a summation and cancellation of individual MUAPs, the EMG provides a reasonable estimate of high-frequency fatigue but an unreliable measure of low-frequency fatigue.     

Motor unit recruitment in the trapezius muscle with special reference to coarse arm movements.

Chronic shoulder pain is common in a variety of occupations. The "Cinderella hypothesis" suggests that the pain originates from damaged type I muscle fibres driven into degenerative processes as a result of too long activation and too short recovery time. The main purpose of this study was to investigate if the same motor units are active during all phases of coarse arm movements. Eight healthy volunteers participated in the study. Intramuscular electromyographic signals were picked up with a four-lead fine wire electrode, during a unilateral straight arm movement. The movement started with either (part 1) an abduction or a flexion, then (2) a movement in the horizontal plane from the sagittal to the frontal plane or vice versa, and finally (3) an adduction or an extension to the start position. The movement cycle was performed in three different speeds, slow, medium, and high, with one, two or five cycles per 20 s, respectively. On an average, the motor unit action potentials (MUAPs) of 6 motor units (range, 1-15) were identified per trail. In total 94% of the MUAP trains that were identified showed firings in all 3 parts of the movements. The findings support the Cinderella hypothesis, although there is a need to further investigate the temporal pattern of long-term motor unit activity.