K. Ming Chan

Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients

Electrical stimulation (ES) of injured peripheral nerves accelerates axonal regeneration in laboratory animals. However, clinical applicability of this intervention has never been investigated in human subjects. The aim of this pilot study was to determine the effect of ES on axonal regeneration after surgery in patients with median nerve compression in the carpal tunnel causing marked motor axonal loss. A randomized control trial was conducted to provide proof of principle for ES-induced acceleration of axon regeneration in human patients. Carpel tunnel release surgery (CTRS) was performed and in the stimulation group of patients, stainless steel electrode wires placed alongside the median nerve proximal to the surgical decompression site for immediate 1 h 20 Hz bipolar ES. Subjects were followed for a year at regular intervals. Axonal regeneration was quantified using motor unit number estimation (MUNE) and sensory and motor nerve conduction studies. Purdue Pegboard Test, Semmes Weinstein Monofilaments, and Levines Self-Assessment Questionnaire were used to assess functional recovery. The stimulation group had significant axonal regeneration 6-8 months after the CTRS when the MUNE increased to 290+/-140 (mean+/-SD) motor units (MU) from 150+/-62 MU at baseline (p<0.05). In comparison, MUNE did not significantly improve in the control group (p>0.2). Terminal motor latency significantly accelerated in the stimulation group but not the control group (p>0.1). Sensory nerve conduction values significantly improved in the stimulation group earlier than the controls. Other outcome measures showed a significant improvement in both patient groups. We conclude that brief low frequency ES accelerates axonal regeneration and target reinnervation in humans.

Double-blind randomized controlled trial of low-level laser therapy in carpal tunnel syndrome

Several studies have suggested that low‐level laser therapy (LLLT) is effective in patients with carpal tunnel syndrome (CTS). In a double‐blind randomized controlled trial of LLLT, 15 CTS patients, 34 to 67 years of age, were randomly assigned to either the control group (n = 8) or treatment group (n =7). Both groups were treated three times per week for 5 weeks. Those in the treatment group received 860 nm galium/aluminum/arsenide laser at a dosage of 6 J/cm2 over the carpal tunnel, whereas those in the control group were treated with sham laser. The primary outcome measure was the Levine Carpal Tunnel Syndrome Questionnaire, and the secondary outcome measures were electrophysiological data and the Purdue pegboard test. All patients completed the study without adverse effects. There was a significant symptomatic improvement in both the control (P = 0.034) and treatment (P =0.043) groups. However, there was no significant difference in any of the outcome measures between the two groups. Thus, LLLT is no more effective in the reduction of symptoms of CTS than is sham treatment. Muscle Nerve 30: 182–187, 2004

Randomized controlled trial of strength training in post‐polio patients

Many post‐polio patients develop new muscle weakness decades after the initial illness. However, its mechanism and treatment are controversial. The purpose of this study was to test the hypotheses that: (1) after strength training, post‐polio patients show strength improvement comparable to that seen in the healthy elderly; (2) such training does not have a deleterious effect on motor unit (MU) survival; and (3) part of the strength improvement is due to an increase in voluntary motor drive. After baseline measures including maximum voluntary contraction force, voluntary activation index, motor unit number estimate, and the tetanic tension of the thumb muscles had been determined, 10 post‐polio patients with hand involvement were randomized to either the training or control group. The progressive resistance training program consisted of three sets of eight isometric contractions, three times weekly for 12 weeks. Seven healthy elderly were also randomized and trained in a similar manner. Changes in the baseline parameters were monitored once every 4 weeks throughout the training period. The trained post‐polio patients showed a significant improvement in their strength (P < 0.05). The magnitude of gain was greater than that seen in the healthy elderly (mean ± SE, 41 ± 16% vs. 29 ± 8%). The training did not adversely affect MU survival and the improvement was largely attributable to an increase in voluntary motor drive. We therefore conclude that moderate intensity strength training is safe and effective in post‐polio patients. Muscle Nerve 27: 332–338, 2003

Contractile properties of human motor units in health, aging, and disease

The primary function of skeletal muscle is to produce force for postural control and movement. Although the contractile properties of the whole muscle are useful functional indicators, they do not accurately reflect the heterogeneity of the constituent motor units (MUs) and their changes in health and disease. However, data on the contractile properties of human MUs, in comparison to other animal species, are relatively sparse. This, in part, is due to greater methodological challenges of in vivo studies of MUs in the human. The purpose of this review is to critically appraise the methods used in humans; to describe the normative data from different muscle groups; to discuss differences between data from healthy humans and other animal species; and, last, to characterize changes of the MU contractile properties in aging, disease, and in response to intervention. Because the spike‐triggered averaging technique can only be used to study the twitch properties, other methods were subsequently developed to measure a wider range of contractile properties. Although there is general agreement between human data and those from other animal species, major differences do exist. Potential reasons for these discrepancies include true biological differences, but differences in the techniques used may also be responsible. Although limited, measurement of MU contractile properties in humans has provided insight into the changes associated with aging and motoneuronal diseases and provides a means of gauging their adaptive capacity for training and immobilization.

Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets.

Peripheral nerve injury is common especially among young individuals. Although injured neurons have the ability to regenerate, the rate is slow and functional outcomes are often poor. Several potential therapeutic agents have shown considerable promise for improving the survival and regenerative capacity of injured neurons. These agents are reviewed within the context of their molecular mechanisms. The PI3K/Akt and Ras/ERK signaling cascades play a key role in neuronal survival. A number of agents that target these pathways, including erythropoietin, tacrolimus, acetyl-l-carnitine, n-acetylcysteine and geldanamycin have been shown to be effective. Trk receptor signaling events that up-regulate cAMP play an important role in enhancing the rate of axonal outgrowth. Agents that target this pathway including rolipram, testosterone, fasudil, ibuprofen and chondroitinase ABC hold considerable promise for human application. A tantalizing prospect is to combine different molecular targeting strategies in complementary pathways to optimize their therapeutic effects. Although further study is needed prior to human trials, these modalities could open a new horizon in the clinical arena that has so far been elusive.

Age-related changes in muscle fatigue resistance in humans.

OBJECTIVE The goal of this study was to compare the relative contributions from the muscle and the central nervous system to muscle fatigue resistance in aging. METHODS Each subject carried out 90 s of sustained maximal voluntary isometric contraction (MVC) of the thumb using the thenar and forearm thumb muscles. Contractile capacity of the thenar muscles was assessed through tetanic stimulation of the median nerve. Interpolated doublets delivered during an MVC represented the overall voluntary activation level while transcranial cortical stimulation with an electromagnetic stimulator was used to assess motor output upstream from the corticomotoneuronal pathway. RESULTS Nine elderly subjects [four females and five males, 70+/-9 years old (mean+/-SD)] and 10 younger subjects (five females and five males, 30+/-6 years old) were tested. After the fatiguing exercise, the elderly groups MVC declined by 29% as opposed to 47% in the younger group (p<0.01). The elderly groups greater fatigue resistance was accounted for by increased fatigue resistance at the muscle level as well as in the central nervous system. At least some of the decline in the central motor drive was upstream from the corticomotoneuronal pathway. CONCLUSION The higher muscle fatigue resistance in the elderly group was attributable to differences in both the peripheral and central nervous systems.

Functional Electrical Stimulation and Spinal Cord Injury

Spinal cord injuries (SCI) can disrupt communications between the brain and the body, resulting in loss of control over otherwise intact neuromuscular systems. Functional electrical stimulation (FES) of the central and peripheral nervous system can use these intact neuromuscular systems to provide therapeutic exercise options to allow functional restoration and to manage medical complications following SCI. The use of FES for the restoration of muscular and organ functions may significantly decrease the morbidity and mortality following SCI. Many FES devices are commercially available and should be considered as part of the lifelong rehabilitation care plan for all eligible persons with SCI.

Motor unit number estimation: A technology and literature review

Introduction: Numerous methods for motor unit number estimation (MUNE) have been developed. The objective of this article is to summarize and compare the major methods and the available data regarding their reproducibility, validity, application, refinement, and utility. Methods: Using specified search criteria, a systematic review of the literature was performed. Reproducibility, normative data, application to specific diseases and conditions, technical refinements, and practicality were compiled into a comprehensive database and analyzed. Results: The most commonly reported MUNE methods are the incremental, multiple‐point stimulation, spike‐triggered averaging, and statistical methods. All have established normative data sets and high reproducibility. MUNE provides quantitative assessments of motor neuron loss and has been applied successfully to the study of many clinical conditions, including amyotrophic lateral sclerosis and normal aging. Conclusions: MUNE is an important research technique in human subjects, providing important data regarding motor unit populations and motor unit loss over time. Muscle Nerve 50: 884–893, 2014

NORMATIVE VALUES AND THE EFFECTS OF AGE, GENDER, AND HANDEDNESS ON THE MOBERG PICK-UP TEST

The Moberg Pick‐Up Test is a standardized test for assessing hand dexterity. Although reduction of sensation in the hand occurs with aging, the effect of age on a subjects performance of the Moberg Pick‐Up Test has not been examined. The primary goal of this study was to examine the impact of aging and, secondarily, the impact of gender and handedness, on performance of the Moberg Pick‐Up Test in 116 healthy subjects. The average time to complete each of the four subsets of the test was analyzed using the Kruskal–Wallis, Mann–Whitney U, and Wilcoxon signed‐rank tests. The results show that hand dexterity of the subjects was significantly affected by age, with young subjects being the fastest and elderly subjects the slowest. Women accomplished the test faster than men, and task performance with the dominant hand was faster than with the non‐dominant hand. Use of normative values established based on age and gender is a valuable objective tool to gauge hand function in patients with different neurologic disorders. Muscle Nerve, 2007

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the β‐frequency band (15–35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non‐invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in β‐band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in β‐band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or β‐band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.