Reliability of a novel neurostimulation method to study involuntary muscle phenomena

Experimental methods involving painful electrical stimulation of a peripheral nerve showed the existence of a minimum stimulation frequency capable of inducing cramp, termed "threshold frequency" (TF). Our aim was to test an alternative method to induce fasciculations and cramps electrically. Two daily sessions of electrical stimulation of the abductor hallucis muscle were performed in 19 volunteers on 3 days: stimulation trains of 150 monophasic square pulses (duration 152 micros) of increasing frequency (current intensity 30% higher than maximal; frequency of the first trial, 4 pps; recovery between trials, 1 min) were delivered to the main muscle motor point until a cramp developed. Once a cramp was induced the protocol was repeated after 30 min. To verify by electromyography that cramp occurred, a surface electrode array was placed between the motor point and the distal tendon. Ambient and skin temperature were kept constant in all sessions. Fasciculations and cramps were elicited in all subjects. We observed the following median (interquartile range) values of TF: day 1 (session 1), 13 (6) pps; day 1 (session 2), 16 (4) pps; day 2 (session 1), 16 (6) pps; day 2 (session 2), 18 (6) pps; day 3 (session 1), 17 (4) pps; day 3 (session 2), 18 (8) pps. TF intersession intraclass correlation coefficients were 0.82, 0.92, and 0.90 for days 1, 2, and 3, respectively. TF interday intraclass correlation coefficient was 0.85. The absence of pain due to the stimulation and the demonstration of TF reliability support the use of our method for the study of involuntary muscle phenomena.     

Superiority of sonographic evaluation of contracted versus relaxed muscle thickness in motor neuron diseases

ObjectiveTo compare the correlations of relaxed and contracted limb muscle thickness with clinical scales in patients with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).MethodsPatients with ALS and SMA were prospectively recruited from December 2018 to November 2019. All patients underwent clinical assessment and sonographic muscle thickness measurement of eight relaxed muscles (biceps brachii, abductor pollicis brevis (APB), first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis), and four contracted muscles (biceps brachii, APB, quadriceps, and tibialis anterior).Results91 patients with ALS and 31 patients with SMA were recruited. Contracted muscle thickness compared to relaxed muscle showed higher reliability and similar or better correlations with muscle strength and clinical scales, especially in ALS patients with hyperreflexia. Strong to very strong correlations with clinical scales were observed with multivariate analysis of relaxed and contracted muscle thickness (0.64–0.87).ConclusionsSonographic evaluation of contracted muscle thickness is an objective measure that correlates with disease burden. It is feasible, quick, valid and reliable, and may be superior to evaluation of relaxed muscles.SignificanceSonographic evaluation of contracted muscle thickness is superior to evaluation of relaxed muscles.     

Electrical stimulation cramp threshold frequency correlates well with the occurrence of skeletal muscle cramps

The minimum electrical stimulation frequency (HZ ) at which a muscle cramps is termed threshold frequency (TF). TF is theorized to represent one's predisposition to cramping; however, TF and cramp occurrence have never been correlated. We hypothesized that TF would be lower in individuals with a cramp history and lower on the second of two days of testing; genetics may partially explain this lower TF. Cramp TF was measured in 19 subjects with (Group 1), and 12 subjects without (Group 2), a cramp history. Group 1 had a lower TF (14.9 ± 1.3 vs. 25.5 ± 1.6 HZ ; P < 0.001) and a higher family history of cramping than Group 2 (89% vs. 27%; P < 0.001). TF was lower on day 2 (18.3 ± 0.26 HZ ) than day 1 (19.7 ± 0.25 HZ ; P = 0.03). Lower TFs are correlated with cramp history, supporting the inference that lower TFs may represent increased predisposition toward cramping. TF may be used to identify individuals at risk of cramping. Muscle Nerve 39: 364–368, 2009     

Botulinum toxin treatment of muscle cramps: A clinical and neurophysiological study

Botulinum toxin is now widely used in the treatment of severla hyperkinetic movement disorders. To evaluate its efficacy in treating muscle cramping syndromes, we studied clinical and neurophysiological variables before and after botulinum toxin injections into calf muscles and small flexor muscles of the foot in patients with an inherited benign crampfasciculation syndrome. At each assessment the clinical severity of cramp was scored and the cramp threshold frequency was measured with repetitive electrical peripheral nerve stimulation. Botulinum toxin injection signifcantly lowered our patients' clinical cramp severity scores (mean ± SD: before, 3.80 ± 0.44; after, 1.40 ± 0.54), left muscle strength unchanged and significanlty increased their cramp threshold frequencies (before, 4.22 ± 2.26 Hz; after, 10.0 ± 3.74 Hz). The clinical beefit induced by botulinum toxin lasted about 3 months. Boutlinum toxin injections also significantly reduced fasciculation potentials in relaxed muscles (before, 0.86 ± 0.19 fasciculations/sec; after, 0.45 ± 0.11 fasciculations/sec). These findings show that local intramuscular injection of botulinum toxin provide effective, safe, and long-lasting relief of cramps possibly by reducing presynaptic cholinergic stimulation of motor nerve terminals and by impairing the input/output function of intrafusal and extrafusal motor end plates.     

Babinski response: stimulus and effector.

This is an electromyographic study of the activity in flexor and extensor muscles of the big toe in 22 patients with a Babinski sign and 49 controls, after mechanical or electrical stimulation of the sole. The results indicate: (1) the Babinski sign is mediated by the extensor hallucis longus (EHL), and not by the extensor hallucis brevis; (2) electrical stimuli may fail to activate the EHL in these patients, and conversely may evoke EHL reflexes in control subjects; (3) in skin reflexes, electrical and mechanical stimuli are not freely interchangeable.     

Oscillatory interaction between the hand area of human primary motor cortex and finger muscles during steady-state isometric contraction

Objective

To compare the magnitudes of β-band coherence between the primary motor cortex (M1) and electromyogram (EMG) for finger muscles, and to determine whether M1–EMG coherence is related to the stability of muscle contraction.

Methods

Cortical signals and EMG during steady-state isometric contraction of right thumb muscle (flexor pollicis brevis (FPB)) or right little finger muscle (flexor digiti minimi brevis (FDMB)) were recorded simultaneously with magnetoencephalography system from 13 right-handed healthy subjects.

Results

The magnitudes of β-band M1–EMG coherence and spectral power in the M1 for the FPB muscle were greater than that for the FDMB muscle (P < 0.001 and P < 0.005, respectively). The stability of EMG for the FPB was higher than that for FDMB (P < 0.001). Greater levels of β-band M1–EMG coherence were associated with higher levels of EMG stability (P < 0.05). The mean dipole sources of the FPB muscle were located more laterally, inferiorly and anteriorly than that of FDMB in the M1 hand area (P < 0.005).

Conclusions

The strength of β-band M1–EMG coherence would play an important role in the stability level of finger-muscle contraction.

Significance

The β-band M1–EMG coherence may reflect effective oscillatory interaction between the M1 and finger muscle during steady-state motor output.     

Effect of sacral-root stimulation on the motor cortex in patients with idiopathic overactive bladder syndrome

AIMS OF THE STUDY: It is presumed that idiopathic overactive bladder syndrome (OBS) is due to visceral hypersensitivity. Sacral-root stimulation can restore the bladder function, but its mechanism remains uncertain. It is well-known that long-term peripheral stimulation can induce brain plasticity. Hence, we investigated whether brain reorganization occurred along with clinical improvement after sacral-root stimulation. MATERIAL AND METHODS: Because toe flexion is the index for monitoring wire placement, we used the flexor hallucis brevis (FHB) as the target muscle. Transcranial magnetic stimulation (TMS) was applied to study motor cortex excitability and the brain mapping of the muscle. RESULTS: Six patients with idiopathic OBS were included in the study. All demonstrated clinical improvement after sacral-root stimulation. Motor cortex excitability and the area of representation for the flexor hallucis brevis muscle increased for at least 30 min after sacral-root stimulation had terminated. CONCLUSION: Our results showed that cerebral activities changed after sacral-root stimulation. The improvement in urinary urgency and urgency perception was probably due in part to brain reorganization.     

Lack of caspase‐3 attenuates immobilization‐induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation

Introduction: Immobilization by casting induces disuse muscle atrophy (DMA). Methods: Using wild type (WT) and caspase‐3 knockout (KO) mice, we evaluated the effect of caspase‐3 on muscle mass, apoptosis, and inflammation during DMA. Results: Caspase‐3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 ± 4% in KO vs. 36 ± 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase‐3 decreased immobilization‐induced increased apoptotic myonuclei (3.2‐fold) and macrophage infiltration (2.2‐fold) in soleus muscle and attenuated increased monocyte chemoattractant protein‐1 mRNA expression (2‐fold in KO vs. 18‐fold in WT) in gastrocnemius. Conclusions: Caspase‐3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways. Muscle Nerve 47: 711–721, 2013     

Mexiletine for muscle cramps in amyotrophic lateral sclerosis: A randomized,double‐blind crossover trial

Introduction: More than 90% of amyotrophic lateral sclerosis (ALS) patients have muscle cramps, but evidence‐based treatments have not been available. Methods: A multicenter, double‐blind, placebo‐controlled crossover trial of mexiletine 150 mg twice daily was conducted in ALS patients requesting treatment of symptomatic muscle cramps. Results: Muscle cramp frequency was reduced in 18 of 20 patients; 13 reductions were attributed to treatment (P < 0.05). The average reduction, based on t tests, was 1.8 cramps per day (a reduction from 5.3 with placebo to 3.5 with mexiletine). The estimated reduction of cramp severity was 15 units on a 100‐unit scale (P = 0.01) from a baseline average of 46. No effect on fasciculations was noted. One patient discontinued the study because of dizziness, and another patient discontinued the study to start open‐label mexiletine therapy. No serious adverse event occurred. Discussion: Mexiletine is a well tolerated and effective medication for controlling the symptom of muscle cramps in ALS. Muscle Nerve 58 : 42–48, 2018     

Exercise induced muscle blood flow is decreased in Charcot–Marie–Tooth disease type 1 polyneuropathy: a power Doppler analysis

Background and purpose

Intramuscular blood flow increases during physical activity and may be quantified immediately following exercise using power Doppler sonography. Post-exercise intramuscular blood flow is reduced in patients with muscular dystrophy, associated with disease severity and degenerative changes. It is not known if intramuscular blood flow is reduced in patients with neuropathy, nor if it correlates with muscle strength and structural changes. The aim was to determine whether blood flow is reduced in patients with polyneuropathy due to Charcot–Marie–Tooth disease type 1 (CMT1) and to compare more affected distal to less affected proximal muscles.

Methods

This was a cross-sectional study including 21 healthy volunteers and 17 CMT patients. Power Doppler ultrasound was used to quantify post-exercise intramuscular blood flow in distal (gastrocnemius) and proximal (elbow flexor) muscles. Intramuscular blood flow was compared to muscle echo intensity, muscle strength, disease severity score, patient age and electromyography.

Results

Polyneuropathy patients showed reduced post-exercise blood flow in both gastrocnemius and elbow flexors compared to controls. A more prominent reduction was seen in the gastrocnemius (2.51% vs. 10.34%, p < 0.0001) than in elbow flexors (4.48% vs. 7.03%, p < 0.0001). Gastrocnemius intramuscular blood flow correlated with muscle strength, disease severity and age. Receiver operating characteristic analysis showed that quantification of intramuscular blood flow was superior to echo intensity for detecting impairment in the gastrocnemius (area under the curve 0.962 vs. 0.738, p = 0.0126).

Conclusion

Post-exercise intramuscular blood flow is reduced in CMT1 polyneuropathy. This reduction is present in both impaired distal and minimally affected proximal muscles, indicating it as an early marker of muscle impairment due to neuropathy.     

Prospective study of muscle cramps in Charcot‐Marie‐Tooth disease

Introduction: This study aims to assess the frequency, location, severity, duration, and fluctuation over time of muscle cramps in Charcot‐Marie‐Tooth disease (CMT). Methods: Inherited Neuropathies Consortium Contact Registry participants recorded the occurrence and characteristics of muscle cramps using an 11‐question survey administered 3 times over 8 weeks. Results: A total of 110 adult patients with CMT completed the survey. Weekly cramp frequency was 9.3 (SD 12.3), and 23% had daily muscle cramps. Twenty‐two percent reported a significant impact on quality of life. Over 8 weeks, the daily frequency and severity of muscle cramps did not change significantly. Conclusions: Patients with CMT have muscle cramps that vary little over an 8‐week period, and they may interfere with quality of life. These data may be useful in the planning of clinical trials of agents to treat adults with CMT‐associated muscle cramps. Muscle Nerve 51: 485–488, 2015     

The influence of muscular lengthening on cramps

Muscle cramps induced by voluntary contraction and by electrical stimulation of the peripheral nerve were studied electrophysiologically in 10 healthy subjects. The aim was to verify that cramps can be evoked by electrical stimulation of peripheral nerve and to clarify the physiological mechanism responsible by analyzing the effect of muscular stretching on cramps. Our results showed: (1) Cramps can be induced even after peripheral nerve block by electrical stimulation distal to the block. (2) No cramps were recorded during or following maximal voluntary contraction without muscular shortening, while 7 of 10 subjects showed a true cramp following maximal effort with shortening of the muscle. (3) Muscle stretching caused a sudden interruption of cramps induced by either voluntary contracion or electrical stimulation of the peripheral nerve, even after the induction of nerve block. (4) The lengthening state of the muscle can strongly influence the possibility of evoking cramps by electrical stimulation of nerve. Our study verifies the experimental model proposed by Lambert in 1969, emphasizing the relevance of frequency of stimulation and confirming the hyposthesis that cramps are of peripheral origin. The effects of muscle stretch and lengthening on cramp interruption and development also have a peripheral mechanism.     

Contribution of reference electrode to the compound muscle action potential

In compound muscle action potential (CMAP) recording, the contribution by the reference electrode is considered to be much smaller than that of the active electrode. We tested this assumption by making quantitative measurements of the signals recorded individually by the active and reference electrodes. In the thenar (median nerve) and extensor digitorum brevis (peroneal nerve) muscles, the reference electrode did contribute less. In the hypothenar muscle (ulnar nerve), however, the signals recorded by active and reference electrodes were of similar amplitude. In tibial nerve conduction studies (NCS), the CMAP from the abductor hallucis (AH) muscle was recorded mainly by the reference electrode; the large-amplitude signal recorded by the reference electrode is attributed to volume-conducted activity from other muscles stimulated during the study. The onset latency of the potential recorded by the active and reference electrodes was similar despite significantly different distances from the stimulating site. Hence, the merits of using anatomic landmarks for defining the distal stimulation site are assessed. When the reference electrode makes a large contribution, the CMAP amplitude may not decrease commensurate with any wasting of the muscle under the active recording electrode, and the need to use another muscle for recording the CMAP for that nerve should be considered.     

Abnormal postexcitatory and interhemispheric motor cortex inhibition in writer's cramp

Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study excitatory and inhibitory stimulation effects in 25 patients with writer's cramp and 25 healthy volunteers. We investigated excitatory and inhibitory corticospinally mediated motor effects in muscles contralateral to the stimulation side as well as interhemispheric inhibition of tonic motor activity in muscles ipsilateral to stimulation. Motor evoked potentials (MEPs) were recorded from both first dorsal interosseus muscles. Motor thresholds at rest and amplitudes and latencies of MEPs obtained during maximal contraction were always bilaterally normal. The duration of postexcitatory inhibition was significantly shortened (168±55 vs. 198±39 ms in normal subjects, P=0.001) and the duration of interhemispheric inhibition prolonged (30.3±6.6 vs. 26±3.9 ms in normal subjects, P < 0.001). Both observations would be compatible with a decreased inhibition of corticospinal and transcallosal outputs of the motor cortex. The results were not influenced by fatigue effects. Abnormal motor cortex inhibition seems to be a generalized phenomenon in writer's cramp since it was detected in both hemispheres and during a simple isometric motor task which did not evoke dystonic symptoms. Received: 28 February 2000 / Received in revised form: 29 June 2000 / Accepted: 1 August 2000     

Motor ‘surround inhibition’ is not correlated with activity in surround muscles

Surround inhibition (SI) is a neural process that has been extensively investigated in the sensory system and has been recently probed in the motor system. Muscle‐specific modulation of corticospinal excitability at the onset of an isolated finger movement has been assumed to reflect the presence of SI in the motor system. This study attempted to characterise this phenomenon in a large cohort of normal volunteers and investigate its relationship with muscle activity in the hand. Corticospinal excitability of the pathways projecting to three hand muscles [first dorsal interosseus (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM)] and electromyographic (EMG) activity of the same muscles were assessed in 31 healthy volunteers during an isolated index finger movement. In the agonist FDI muscle both corticospinal excitability and EMG activity were found to be increased at the onset of the movement (P < 0.001 and P < 0.001, respectively). On the contrary, in the surround ADM, there was dissociation between the corticospinal excitability (decreased: P < 0.001) and EMG activity (increased: P < 0.001). Cross‐correlation analysis of the EMG activity showed that neuronal signals driving the agonist and surround muscles are not synchronised when SI is present. The results suggest a distinctive origin of the neuronal signals driving the agonist and surround muscles. In addition, they indicate that cortical output might be simultaneously modulated by voluntary and non‐voluntary activity, generated in cortical and subcortical structures, respectively.     

Quantitative assessment of motor impairment and surgical outcome in Hirayama disease with proximal involvement using motor unit number index

ObjectiveTo assess the feasibility of motor unit number index (MUNIX) in quantitatively evaluating Hirayama disease (HD) with proximal involvement and to identify the effectiveness of anterior cervical fusion (ACF) in treating atypical HD with proximal involvement.MethodsThis study included 28 atypical HD patients with proximal involvement (proximal-distal vs. distal-proximal groups: 5 vs. 23) and 41 healthy controls. All patients underwent pre- and postoperative 1-year MUNIX tests on abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB) and deltoid (Del). The disabilities of arm, shoulder and hand (DASH) and Medical Research Council (MRC) scales were also performed in these patients before and one year after operation.ResultsPreoperatively, the patients in the distal-proximal group showed reduced compound muscle action potential (CMAP), decreased MUNIX and increased motor unit size index (MUSIX) in bilateral distal muscles and symptomatic-side proximal muscles (P < 0.05), and similar abnormalities were also observed in ADM, BB and Del on the symptomatic side in the proximal-distal groups (P < 0.05). Postoperative follow-up analysis identified increased MUNIX in the symptomatic-side proximal muscles with improved motor function in the proximal-distal groups (P < 0.05), and distal-proximal group patients showed an increase in both CMAP and MUSIX in the symptomatic-side proximal muscles (P < 0.05).ConclusionsMUNIX may serve as an available supplementary test to quantitatively evaluate the motor dysfunction and treatment outcome in HD with proximal involvement. ACF procedures can effectively treat these atypical HD patients, especially for those whose symptoms started in proximal muscles.     

A noninvasive technique to assess completeness of spinal cord lesions in humans

The effect of scalp stimulation delivered through electrodes overlying the motor cortex was evaluated in five healthy subjects and six patients with traumatic spinal cord injury. The latency to the onset of the electromyographic response was measured in the biceps brachii and abductor pollicis brevis muscles. In all the patients, latencies to the muscle (biceps brachii) whose innervation originated above the lesion were in the normal range; whereas, latencies to the muscle (abductor pollicis brevis) whose innervation originated below the lesion were prolonged. Electromyographic signals were recorded in muscles which showed no voluntary motor activity. No lateral differences in latencies were found in healthy subjects; however, in the patients, significant differences were obtained between the right and left abductor pollicis brevis muscles. The results of this study demonstrate that the spinal cord of patients with a lesion deemed to be clinically complete, contains nerve fibers which descend through the lesion and are capable of conveying impulses leading to muscle contraction.     

The effect of cutaneous input on intracortical inhibition in focal task‐specific dystonia

In normal subjects short interval intracortical inhibition (SICI) is topographically modulated by cutaneous input, which may be important for focusing muscle activation during tasks. In patients with writer's cramp, a task‐specific focal dystonia characterized by inappropriate and excessive muscle activation of the upper limb during certain motor tasks, intracortical inhibition is reduced at rest and lacks the normal topographically‐specific modulation during motor tasks. In the present study we investigated whether cutaneous input modulated SICI in a group of patients with writer's cramp and a control group of subjects. Electromyographic recordings were made from the right first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles. Brief electrical stimuli were applied to either digit II or digit V with ring electrodes. SICI was investigated using a paired transcranial magnetic stimulation paradigm employing interstimulus intervals of 1–15 ms. Cutaneous input from both digit II and digit V modulated motor evoked potentials and SICI in a topographically‐specific manner in control subjects. In contrast, cutaneous input failed to modulate motor evoked potentials or SICI in the focal hand dystonia patients. These results provide further evidence of abnormal sensorimotor integration in focal hand dystonia. © 2007 Movement Disorder Society     

Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in Amyotrophic Lateral Sclerosis

Objective

Motor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with Amyotrophic Lateral Sclerosis (ALS). However, it is unclear whether MUNIX also detects motor unit loss in strong, non-wasted muscles.

Provocation tests in doppler ultrasonography for carpal tunnel syndrome

Introduction: Doppler ultrasonography (DU) has recently been shown to be useful in imaging carpal tunnel syndrome (CTS). In this study, we aim to characterize the changes seen after exercise and electrical stimulation. Methods: Five patients with CTS were recruited with 5 age‐matched subjects. DU was used to visualize the median nerve, flexor tendon, and bone at base line and after 1 minute of: (a) median nerve motor stimulation, (b) median nerve sensory stimulation, (c) abductor pollicis brevis contraction, and (d) adductor digiti minimi contraction. Results: Blood flow in the median nerve was greater after APB exercise. Furthermore, blood flow in the median nerve was greater in cases than controls after APB exercise. At baseline, blood flow in the flexor tendon was greater in cases than controls. Conclusions: While limited by sample size, this study demonstrates that exercise of median innervated muscles may be useful in enhancing diagnostic utility of DU for CTS. Muscle Nerve, 2013