Peripheral nerve injuries are common and frequently result in incomplete functional recovery even with optimal surgical treatment. Permanent motor and sensory deficits are associated with significant ...patient morbidity and socioeconomic burden. Despite substantial research efforts to enhance peripheral nerve regeneration, few effective and clinically feasible treatment options have been found. One promising strategy is the use of low frequency electrical stimulation delivered perioperatively to an injured nerve at the time of surgical repair. Possibly through its effect of increasing intraneuronal cyclic AMP, perioperative electrical stimulation accelerates axon outgrowth, remyelination of regenerating axons, and reinnervation of end organs, even with delayed surgical intervention. Building on decades of experimental evidence in animal models, several recent, prospective, randomized clinical trials have affirmed electrical stimulation as a clinically translatable technique to enhance functional recovery in patients with peripheral nerve injuries requiring surgical treatment. This paper provides an updated review of the cellular physiology of electrical stimulation and its effects on axon regeneration, Level I evidence from recent prospective randomized clinical trials of electrical stimulation, and ongoing and future directions of research into electrical stimulation as a clinically feasible adjunct to surgical intervention in the treatment of patients with peripheral nerve injuries.
ABSTRACT
Introduction: The goal of this study is to test the hypothesis that single motor unit action potentials (SMUPs) originating from other ulnar nerve–innervated intrinsic hand muscles can ...inflate the motor unit number estimation (MUNE) of the hypothenar muscles. Methods: Using the multiple point stimulation method, SMUPs recorded over the hypothenar muscles from distant origins were characterized through multichannel recordings. The MUNE calculated using only the hypothenar SMUPs was compared with estimations based on the whole ensemble. Results: Of the 41 studies performed, distant SMUPs represented 17 ± 9.5% (mean ± SD) of the overall sample. MUNE calculated using only hypothenar SMUPs was 423 ± 204, compared with 537 ± 290 if all SMUPs were included (P < 0.05). The extent of increase in MUNE was highly correlated with the proportion of distant SMUPs found (r = 0.89, P < 0.05). Discussion: Erroneous inclusion of SMUPs from distant muscles can significantly distort the MUNE results. Muscle Nerve 59:337–341, 2019
Environmental management has been researching extensively in the last two decades. Pressure from environmental regulations or policies plays an important role to boost environmental management ...practices. Nevertheless, the relationship between such pressure and the ultimate firm performance is not very obvious. Although green product innovation has been recognized as a predictor to improve environment performance, there is a lack of discussion in the literature to examine the mediating effect of green product innovation between the aforementioned pressure and firm performance. Additionally, most previous studies adopted a static view which ignores the implications on external dynamic factors in many empirical studies. In this connection, this study contributes to the field of knowledge by filling these two gaps. More specifically, this study: (i) examines the effect of green product innovation on the relationship between pressure of environmental regulations (or policies) and firm performance; and (ii) evaluates the moderating effect of environmental dynamism on the relationship between green production innovation and firm performance. A questionnaire survey is conducted in an emerging country, China, to verify the hypotheses.
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.
•Peripheral nerve injuries are common.•Although peripheral nerves can regenerate, functional outcomes are often poor.•Understanding the molecular mechanisms of nerve regeneration allows targeted therapy.•Several agents have shown promise in animal models of nerve injury.•We review these agents and discuss the feasibility of future clinical application.
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 Levine's 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.
Objective
Brief postsurgical electrical stimulation (ES) has been shown to enhance peripheral nerve regeneration in animal models following axotomy and crush injury. However, whether this treatment ...is beneficial in humans with sensory nerve injury has not been tested. The goal of this study was to test the hypothesis that ES would enhance sensory nerve regeneration following digital nerve transection compared to surgery alone.
Methods
Patients with complete digital nerve transection underwent epineurial nerve repair. After coaptation of the severed nerve ends, fine wire electrodes were implanted before skin closure. Postoperatively, patients were randomized to receiving either 1 hour of 20Hz continuous ES or sham stimulation in a double‐blinded manner. Patients were followed monthly for 6 months by a blinded evaluator to monitor physiological recovery of spatial discrimination, pressure threshold, and quantitative small fiber sensory testing. Functional disability was measured using the Disability of Arm, Shoulder, and Hand questionnaire.
Results
A total of 36 patients were recruited, with 18 in each group. Those in the ES group showed consistently greater improvements in all sensory modalities by 5 to 6 months postoperatively compared to the controls. Although there was a trend of greater functional improvements in the ES group, it was not statistically significant (p > 0.01).
Interpretation
Postsurgical ES enhanced sensory reinnervation in patients who sustained complete digital nerve transection. The conferred benefits apply to a wide range of sensory functions. Ann Neurol 2015;77:996–1006
Aims
To determine whether diabetes distress or depression screening better predict increased hemoglobin A1c (HbA1c) and to assess interactions with age, sex, race, obesity, and insurance status.
...Background
Diabetes distress is a negative emotional reaction to diabetes, diabetes complications, self-management demands, unresponsive providers, and/or poor interpersonal relationships. Guidelines recommend annual depression screening, however diabetes distress may be mistaken for depression.
Method
Depression (PHQ-9) and diabetes distress (PAID-T) scores from self-administered tests were studied in 313 patients with type 1 diabetes (T1D) between the ages of 13–17. Spearman correlations and robust rank order multivariable regression analysis were used to assess relationships to age, duration, HbA1c. Kruskal–Wallis test was used to assess differences between sexes, races, and insurance status. Receiver operator curves (ROC) were constructed to see whether PAID-T or PHQ-9 scores more closely predicted HbA1c greater than 9%.
Results
HbA1c was more strongly correlated with PAID-T (
r
s
= 0.37,
p
< 0.01), than PHQ-9 (
r
s
= 0.27,
p
< 0.01) scores. Area under ROC curve for poor HbA1c was 0.75 for PAID and 0.64 for PHQ-9. PAID-T and PHQ-9 scores were increased in females and subjects with public insurance and both were significantly related to HbA1c even when accounting for age, sex, race obesity, and insurance status. PHQ-9 and PAID-T scores correlated with BMI-Z scores in Blacks, but not Whites.
Conclusions
Both depression and diabetes distress are associated with increased HbA1c in adolescents with T1D, though distress is more so. Diabetes distress and depression should be routinely assessed in T1D adolescents, particularly those with public insurance.
ABSTRACT
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
Abstract
BACKGROUND
Patients with severe cubital tunnel syndrome often have poor functional recovery with conventional surgical treatment. Postsurgical electrical stimulation (PES) has been shown to ...enhance axonal regeneration in animal and human studies.
OBJECTIVE
To determine if PES following surgery for severe cubital tunnel syndrome would result in better outcomes compared to surgery alone.
METHODS
Patients with severe cubital tunnel syndrome in this randomized, double-blind, placebo-controlled trial were randomized in a 1:2 ratio to the control or stimulation groups. Control patients received cubital tunnel surgery and sham stimulation, whereas patients in the stimulation group received 1-h of 20 Hz PES following surgery. Patients were assessed by a blinded evaluator annually for 3 yr. The primary outcome was motor unit number estimation (MUNE) and secondary outcomes were grip and key pinch strength and McGowan grade and compound muscle action potential.
RESULTS
A total of 31 patients were enrolled: 11 received surgery alone and 20 received surgery and PES. Three years following surgery, MUNE was significantly higher in the PES group (176 ± 23, mean + SE) compared to controls (88 ± 11, P < .05). The mean gain in key pinch strength in the PES group was almost 3 times greater than in the controls (P < .05). Similarly, other functional and physiological outcomes showed significantly greater improvements in the PES group.
CONCLUSION
PES enhanced muscle reinnervation and functional recovery following surgery for severe cubital tunnel syndrome. It may be a clinically useful adjunct to surgery for severe ulnar neuropathy, in which functional recovery with conventional treatment is often suboptimal.
Graphical Abstract
Graphical Abstract
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