Muscle Velocity Recovery Cycles Research Articles

O-26 Muscle velocity recovery cycles in neurogenic muscles

O-26 Muscle velocity recovery cycles in neurogenic muscles

MScanFit motor unit number estimation (MScan) and muscle velocity recovery cycle recordings in amyotrophic lateral sclerosis patients

ObjectiveMotor Unit Number Estimation (MUNE) methods, such as the recently developed MScanFit MUNE (MScan), may be valuable in tracking motor unit loss in ALS. Muscle Velocity Recovery Cycles (MVRCs) provide information about muscle membrane properties and can reveal disease-related changes.This study was undertaken to test the applicability of MScan to the anterior tibial muscle (TA) and to test whether the MVRCs could improve understanding of ALS pathophysiology. MethodsTwenty-six ALS patients and 25 healthy controls were evaluated by quantitative electromyography, nerve conduction study and the two novel methods: MScan and MVRC; all in the TA and peroneal nerve. ResultsThe estimated number of motor units for ALS patients (Median: 45, interquartile range: 28.5–76.5) was significantly lower than for the controls (117, 96.0–121.0) (P = 2.19 × 10−7). Unit size was increased only when amplitudes were expressed as percentage of CMAP. Of MVRC measurements, only relative refractory period was significantly abnormal in patients. ConclusionMScanFit MUNE gives a sensitive and quantitative measure of loss of TA motor units in ALS. Muscle fiber membrane properties are mostly unaffected, despite substantial denervation, presumably due to collateral reinnervation. SignificanceMScan is suitable for detecting motor unit loss in TA. MVRCs do not provide new insights in ALS.

T79. Muscle velocity recovery cycles in detection of early axonal involvement in guillain barre syndrome

Introduction Electrophysiological changes in Guillain Barre Syndrome (GBS) are usually first seen 2–3 weeks after disease onset. Therefore, the initial diagnosis may be uncertain and differentiation between the demyelinating (Acute Inflammatory Demyelinating Polyneuropathy-AIDP) and axonal (Acute Motor Axonal Neuropathy-AMAN) types may be difficult. Muscle Velocity Recovery Cycles (MVRC) enable in vivo assessment of muscle membrane properties. We aimed in this study to examine whether MVRC may detect early changes in patients with GBS and may enable differentiation between AIDP and AMAN. Methods Nine patients with GBS symptoms (5 AIDP, 3 AMAN and 1 acute CIDP (chronic inflammatory demyelinating polyneuropathy)) and 24 age- and sex-matched healthy controls were prospectively included. In addition to conventional nerve conduction studies (NCS) and electromyography, all patients were examined by MVRC in the anterior tibial muscle using Qtrac-software in the 1st week of symptom-start. A 4th-week control examination by NCS and electromyography was done in all patients, while MVRC was done in 4 (3 AIDP and 1 AMAN). MVRC parameters consisted of muscle relative refractory period (MRRP) and early, late and residual supernormality after 1, 2 or 5 conditioning stimuli. Results None of the patients had spontaneous activity in the 1st week examination. MRRP was significantly prolonged in patients compared to healthy controls, and early and late supernormality after 2 and 5 conditioning stimuli were decreased (non-parametric t test, p 0.05). Conclusion Changes in MVRC already in the 1st week of symptoms before presence of spontaneous activity may suggest early detection of axonal involvement in GBS. Additionally, MVRC could distinguish AIDP from AMAN, however this could also be due to severity of the disease in these patients. These results may suggest the potential use of MVRC in clinics. Future studies are needed with larger patient groups.

S130. Muscle velocity recovery cycles in intensive care unit patients

Introduction Critical illness myopathy is a disabling condition that develops in critically ill patients and presents as diffuse muscle weakness and failure to wean from mechanical ventilation. Muscle Velocity Recovery Cycles (MVRC) enable in vivo assessment of muscle membrane properties. We aimed in this study to examine whether MVRC may detect changes in patients with delayed wean from mechanical ventilation. Methods Six patients (mean age: 52.4 ± 5.8) with failure to wean from mechanical ventilation and 24 healthy controls (mean age: 53.2 ± 3.2) were prospectively included. In addition to conventional nerve conduction studies (NCS) and electromyography, all patients were examined by MVRC in the anterior tibial muscle using Qtrac-software. MVRC parameters consisted of muscle relative refractory period (MRRP) and early and late supernormality after 1, 2 or 5 conditioning stimuli. Results Motor NCS of peroneal and tibial and sensory NCS of sural nerves were normal. None of the patients had spontaneous activity and quantitative motor unit potential analysis was normal. MRRP was significantly prolonged in patients (5.9 ± 0.7) compared to healthy controls (3.6 ± 0.09), and early supernormality was lower in patients than healthy controls after 2 (5.1 ± 1.1 vs 11.3 ± 0.4) and 5 (4.6 ± 1.1 vs 13.5 ± 0.4) conditioning stimuli. Similarly, late supernormality was decreased in patients compared to healthy controls after 1 (2.4 ± 0.5 vs 3.9 ± 0.2), 2 (1.4 ± 0.4 vs 2.8 ± 0.1) and 5 (3.1 ± 0.8 vs 7.9 ± 0.2) conditioning stimuli (t test, p Conclusion Changes in MVRC in patients with failure to wean from mechanical ventilation may suggest critical illness myopathy in these patients. MVRC may detect changes in the muscle membrane before spontaneous activity and motor unit potential changes are seen. Future studies with larger patient groups and follow-up examinations are needed.

Sarcolemmal excitability changes in normal human aging.

The exact mechanisms underlying the loss of skeletal muscle bulk and power with normal human aging are not well established. Recording of muscle velocity recovery cycles (MVRCs) is an in-vivo neurophysiologic technique we employed to assess the impact of age on sarcolemmal excitability. MVRC recordings were obtained from tibialis anterior (n = 74) and rectus femoris (n = 32) muscles in 74 healthy subjects (18-84 years, median age 35 years, interquartile range 29-55 years). Increasing age was linearly associated with longer muscle relative refractory period (MRRP) and reduced early supernormality (ESN) in both tibialis anterior (MRRP: r2 = 0.38, P < 0.001; ESN: r2 = 0.33, P < 0.001) and rectus femoris (MRRP: r2 = 0.30, P = 0.002; ESN: r2 = 0.19, P = 0.01) muscles. The results are consistent with progressive depolarization of the resting sarcolemmal potential with normal aging. This may be an important mechanism in explaining age-related muscle decline. Muscle Nerve 57: 981-988, 2018.

Muscle membrane properties in A pig sepsis model: Effect of norepinephrine.

Sepsis-induced myopathy and critical illness myopathy are common causes of muscle weakness in intensive care patients. This study investigated the effect of different mean arterial blood pressure (MAP) levels on muscle membrane properties following experimental sepsis. Sepsis was induced with fecal peritonitis in 12 of 18 anesthetized and mechanically ventilated pigs. Seven were treated with a high (75-85 mmHg) and 5 were treated with a low (≥60 mmHg) MAP target for resuscitation. In septic animals, resuscitation was started 12 h after peritonitis induction, and muscle velocity recovery cycles were recorded 30 h later. Muscles in the sepsis/high MAP group showed an increased relative refractory period and reduced early supernormality compared with the remaining septic animals and the control group, indicating membrane depolarization and/or sodium channel inactivation. The membrane abnormalities correlated positively with norepinephrine dose. Norepinephrine may contribute to sepsis-induced abnormalities in muscle by impairing microcirculation. Muscle Nerve 57: 808-813, 2018.

Sarcolemmal excitability in the myotonic dystrophies.

Chloride conductance disturbances contribute to sarcolemmal dysfunction in myotonic dystrophy type 1 (DM1) and type 2 (DM2). Studies using muscle velocity recovery cycles (MVRCs) suggest Na+ /K+ -adenosine triphosphatase activation becomes defective in advanced DM1. We used MVRCs to investigate muscle excitability in DM1 and DM2. MVRCs were measured for patients with mild (n = 8) and advanced (n = 11) DM1, DM2 (n = 4), and normal controls (n = 30). Residual supernormality after multiple conditioning stimuli was increased in DM2 and advanced DM1. Advanced DM1 was distinguished by increases in muscle relative refractory period (MRRP) and reduced early supernormality as well as peak amplitude decrements for the first and last responses in train during repetitive stimulation. Prolongation of the MRRP indicates that depolarization of the resting muscle membrane potential occurs in advanced DM1, with possible implications for future therapeutic approaches. Muscle Nerve 57: 595-602, 2018.

In vivo assessment of muscle membrane properties in the sodium channel myotonias.

The gain-of-function mutations that underlie sodium channel myotonia (SCM) and paramyotonia congenital (PMC) produce differing clinical phenotypes. We used muscle velocity recovery cycles (MVRCs) to investigate membrane properties. MVRCs and responses to trains of stimuli were compared in patients with SCM (n = 9), PMC (n = 8), and normal controls (n = 26). The muscle relative refractory period was reduced in SCM, consistent with faster recovery of the mutant sodium channels from inactivation. Both SCM and PMC showed an increased early supernormality and increased mean supernormality following multiple conditioning stimuli, consistent with slowed sodium channel inactivation. Trains of fast impulses caused a loss of amplitude in PMC, after which only half of the muscle fibers recovered, suggesting that the remainder stayed depolarized by persistent sodium currents. The differing effects of mutations on sodium channel function can be demonstrated in human subjects in vivo using this technique. Muscle Nerve 57: 586-594, 2018.

O99 Muscle velocity recovery cycles in neurogenic muscles

Muscle Velocity Recovery Cycles (MVRC) enable assessment of muscle membrane properties. MVRC has been studied in some myopathies, however, the method has never been tested in neurogenic muscles. We aimed in this study to examine whether MVRC differ in neurogenic and normal muscles and how MVRC variables correlate to the incidence of spontaneous activity (SA) in electromyography (EMG). Twenty-five patients with confirmed peroneal neuropathy (twenty) or L5 root lesion (five) were prospectively included. In addition to EMG, MVRC was done in anterior tibial muscle using Qtrac-software. MVRC parameters comprised muscle relative refractory period (MRRP) and early, late and residual supernormality after 1, 2 or 5 conditioning stimuli. Results were compared to 16 age- and sex-matched healthy subjects (HS). There was significant correlation between the incidence of SA and MRRP (r = 0.54) and early and late supernormality most pronounced in early supernormality after 5 conditioning stimulation (r = 0.64) (p < 0.001). The same MVRC parameters differed between patients and HS (t-test, p < 0.05). In contrast, residual supernormality did not differ between groups and there was no correlation to SA. Significantly prolonged MRRP and pronounced slowing in propagation velocity in early supernormal period suggest lower depolarization threshold in the denervated fibers. This is supported by significant correlation to incidence of SA in EMG. MVRC may be a potential diagnostic tool for electrodiagnosis of neuromuscular disorders and may provide information in understanding muscle pathophysiology. Future studies are required with larger patient groups with comparison of different nerve and muscle disorders.

Force training induces changes in human muscle membrane properties.

Human muscle membrane properties can be assessed in vivo by recording muscle velocity recovery cycles (MVRCs). This study was undertaken to study the effect of muscle force training on MVRC parameters. MVRCs with 1 to 5 conditioning stimuli were recorded from brachioradialis muscle before and after 2 weeks of muscle force training in 12 healthy subjects. The effects of training on relative refractory period and early and late supernormality were quantified. Force training induced a reduction of relative refractory period (P < 0.0001), while early supernormality was increased (P < 0.02) and peaked earlier (P < 0.01). Late supernormality and the increases in late supernormality due to 2 and 5 conditioning stimuli remained unchanged. Muscle force training leads to hyperpolarization of the resting muscle membrane potential, probably caused by an increase in the number of sodium pump sites. Muscle Nerve 54: 144-146, 2016.

In vivo assessment of muscle membrane properties in myotonic dystrophy.

Myotonia in myotonic dystrophy types 1 (DM1) and 2 (DM2) is generally attributed to reduced chloride-channel conductance. We used muscle velocity recovery cycles (MVRCs) to investigate muscle membrane properties in DM1 and DM2, using comparisons with myotonia congenita (MC). MVRCs and responses to repetitive stimulation were compared between patients with DM1 (n = 18), DM2 (n = 5), MC (n = 18), and normal controls (n = 20). Both DM1 and DM2 showed enhanced late supernormality after multiple conditioning stimuli, indicating delayed repolarization as in MC. Contrary to MC, however, DM1 showed reduced early supernormality after multiple conditioning stimuli, and weak DM1 patients also showed abnormally slow latency recovery after repetitive stimulation. These findings support the presence of impaired chloride conductance in both DM1 and DM2. The early supernormality changes indicate that sodium currents were reduced in DM1, whereas the weakness-associated slow recovery after repetitive stimulation may provide an indication of reduced Na(+) /K(+) -ATPase activation. Muscle Nerve 54: 249-257, 2016.

4. Muscle excitability in Myotonic Dystrophy type 1

The measurement of muscle velocity recovery cycles (MVRCs) is now an established technique that has been used to determine the excitability properties of skeletal muscle in vivo in a variety of myopathic conditions. Patterns of change in the velocity of muscle action potentials generated by different temporal combinations of prior conditioning impulses sensitively reflect membrane polarization and the function of T-tubules. Further, studies in myotonia congenita (MC) have yielded fundamental insights into the function of the muscle chloride channel itself, in both MC and in general. Myotonic dystrophy type 1 (DM1) is an inherited disorder of RNA splicing that alters the transcription of muscle chloride channels, thereby affecting function and causing myotonia. However, a number of other genes encoding muscle proteins that may determine excitability are similarly mis-spliced. We studied the excitability properties of skeletal muscle in DM1, aiming to gain further insight into the determinants of muscle membrane dysfunction in this disorder. Control studies were established and a cohort of DM1 compared to these. The results of the studies will be presented.

Muscle velocity recovery cycles: Comparison between surface and needle recordings.

Recording of muscle velocity recovery cycles (MVRCs) has been developed as a technique to investigate the pathophysiology of muscle diseases. MVRCs have been measured by direct muscle stimulation and concentric electromyographic needle recording. This study was undertaken to determine whether recordings can be made with surface electrodes. MVRCs with 1 and 2 conditioning stimuli were recorded simultaneously with concentric needle and surface electrodes from the brachioradialis muscle in 12 healthy volunteers. Muscle relative refractory period, early and late supernormality, and extra-late supernormality were compared between the recording techniques. Surface recordings were possible in all subjects. The multifiber action potentials recorded with surface electrodes were smaller than those recorded with needles, but there was no significant difference between any of their MVRC properties. MVRCs can be recorded with surface electrodes in healthy subjects. The use of surface electrodes may facilitate the technique of recording MVRCs.

Muscle channelopathies: recent advances in genetics, pathophysiology and therapy.

This article reviews recent advances in clinical, genetic, diagnostic and pathophysiological aspects of the skeletal muscle channelopathies. Genetic advances include the use of the minigene assay to confirm pathogenicity of splice site mutations of CLC-1 chloride channels and a new gene association for Andersen-Tawil syndrome. Mutations causing a gating pore current have been established as a pathomechanism for hypokalaemic periodic paralysis. Mutations in nonchannel genes, including the mitochondrial mATP6/8 genes, have been linked to channelopathy-like episodic weakness. Advances in diagnostic tools include the use of MRI and muscle velocity recovery cycles to evaluate myotonia congenita patients. Specific neonatal presentations of sodium channel myotonia are now well documented. An international multicentre placebo-controlled randomized clinical trial established that mexiletine is an effective therapy in the nondystrophic myotonias. This is the first evidence-based treatment for a skeletal muscle channelopathy. Recent evidence in mouse models indicated that bumetanide can prevent attacks of hypokalaemic periodic paralysis, but this has not yet been tested in patient trials. Advances in genetic, clinical, diagnostic and pathomechanistic understanding of skeletal muscle channelopathies are being translated into improved therapies. Mexiletine is the first evidence-based treatment for nondystrophic myotonias. Bumetanide is effective in preventing attacks in mouse models of hypokalaemic periodic paralysis and now needs to be tested in patients.

Early changes of muscle membrane properties in porcine faecal peritonitis.

IntroductionSepsis-induced myopathy and critical illness myopathy (CIM) are possible causes of muscle weakness in intensive care patients. They have been attributed to muscle membrane dysfunction. The aim of this study was to investigate membrane properties in the early stage of experimental sepsis by evaluating muscle excitability.MethodsIn total, 20 anaesthetized and mechanically ventilated pigs were randomized to either faecal peritonitis (n = 10) or to non-septic controls (n = 10). Resuscitation with fluids and vasoactive drugs was started 3 hours after peritonitis induction. Muscle membrane properties were investigated by measuring muscle velocity recovery cycles before induction of peritonitis as well as 6, 18 and 27 hours thereafter. Muscle relative refractory period (MRRP) and early supernormality (ESN) were assessed.ResultsPeritonitis lasting 27 hours was associated with an increase of MRRP by 28% from 2.38 ± 0.18 ms (mean ± SD) to 3.47 ± 1.79 ms (P <0.01) and a decrease of ESN by 31% from 9.64 ± 2.82% to 6.50 ± 2.64% (P <0.01). ESN reduction was already apparent 6 hours after induction of peritonitis. Values in controls did not show any significant alterations.ConclusionsMuscle membrane abnormalities consistent with membrane depolarization and/or sodium channel inactivation occurred within 6 hours of peritonitis induction. This indicates that changes that have been described in established sepsis-induced myopathy and/or CIM start early in the course of sepsis. Muscle excitability testing facilitates evaluation of the time course of these changes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0484-2) contains supplementary material, which is available to authorized users.

Chloride channels in myotonia congenita assessed by velocity recovery cycles

Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected. MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal controls. MC patients exhibited increased early supernormality, but this was prevented by treatment with sodium channel blockers. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation. MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that, in dominant MC, the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC-1 activation curve.

Membrane dysfunction in Andersen‐Tawil syndrome assessed by velocity recovery cycles

Andersen-Tawil syndrome (ATS) due to Kir2.1mutations typically manifests as periodic paralysis, cardiac arrhythmias and developmental abnormalities but is often difficult to diagnose clinically. This study was undertaken to determine whether sarcolemmal dysfunction could be identified with muscle velocity recovery cycles (MVRCs). Eleven genetically confirmed ATS patients and 20 normal controls were studied. MVRCs were recorded with 1, 2, and 5 conditioning stimuli and with single conditioning stimuli during intermittent repetitive stimulation at 20 Hz, in addition to the long exercise test. ATS patients had longer relative refractory periods (P < 0.0001) and less early supernormality, consistent with membrane depolarization. Patients had reduced enhancement of late supernormality with 5 conditioning stimuli (P < 0.0001), and less latency reduction during repetitive stimulation (P < 0.001). Patients were separated completely from controls by combining MVRC and repetitive stimulation. MVRCs combined with repetitive stimulation differentiated ATS patients from controls more effectively than the conventional long-exercise test.

Temperature dependency of human muscle velocity recovery cycles

Velocity recovery cycles (VRCs) of human muscle action potentials have been proposed as a new technique for studying muscle membrane function. This study was undertaken to determine the temperature dependency of VRC parameters. VRCs with 1 conditioning stimulus were recorded repeatedly from brachioradialis muscle during cooling, and intramuscular temperature was recorded. VRCs in 6 normal volunteers were measured at 1°C intervals from 34°C to 28°C. The effects of temperature on relative refractory period and early and late supernormality were quantified. Muscle VRC curves shift progressively upward and to the right with cooler temperatures. The most sensitive parameter to temperature changes was relative refractory period, whereas early supernormality was rather insensitive. Late supernormality was unaffected by temperature changes. Knowledge of temperature-induced changes of muscle VRC parameters is essential for future studies. Thus, the results of this study provide a firm basis for clinical studies with this technique.

Muscle velocity recovery cycles: Effects of repetitive stimulation on two muscles

We sought to characterize the excitability properties of tibialis anterior (TA) and brachioradialis (BR) muscles at rest and during electrically induced muscle activation in normal subjects. Two centers recruited 10 subjects each. Multi-fiber velocity recovery cycles (VRCs) were recorded from TA (both centers) and BR (one center). VRCs were assessed at rest and during repetitive stimulation (intermittent 20 Hz for 6 min). Changes in latency and peak amplitude of the muscle action potential induced by a frequency ramp to 30 Hz were also characterized. Excitability properties recorded from TA were very similar between centers. Repetitive stimulation generated marked excitability changes, which were similar between TA and BR. Standardized tests of muscle VRCs and responses to repetitive stimulation can provide consistent measures of membrane function and may encourage their wider use in clinical neurophysiology to investigate the pathophysiology of neuromuscular disorders.

Validity of multi-fiber muscle velocity recovery cycles recorded at a single site using submaximal stimuli

ObjectiveTo examine the validity of multi-fiber muscle velocity recovery cycles (VRCs) recorded by direct muscle stimulation with submaximal stimuli. MethodsVRCs were recorded from tibialis anterior muscle in normal volunteers with 1, 2 and 5 conditioning stimuli. Recordings were made with 6 different amplitudes of conditioning stimuli. Recordings were also made with two recording electrodes, at least 15mm apart. ResultsMuscle VRCs in 6 subjects were not significantly different for conditioning stimuli between 80% and 150% of test stimulus amplitude. When recorded at two sites in 9 subjects, VRCs were similar when estimated over the shorter distance, the longer distance, and from the conduction time between the two electrodes. ConclusionsMulti-fiber muscle VRCs can be reliably recorded with a single recording electrode and with equal amplitude conditioning and test stimuli. SignificanceClinical neurophysiologists can be assured that this new method of testing muscle membrane properties provides valid and robust measurements on normal muscles.