神经传导测定技术对腕管综合征病情评估的价值

目的:近年来腕管综合征发病率逐年升高,然而其慢性、隐匿性不易引起人们的重视,发现时往往已造成较大的危害。本文探讨腕管综合征的神经传导测定对病情评估的临床价值,旨在为患者腕管综合征早期发现和后续治疗提供进一步的临床参考依据。方法:选取我院124例确诊的腕管综合征患者。其中无大鱼际肌萎缩者有64例,并选取平均年龄相近的64例正常人作为对照(组A);有大鱼际肌畏缩者60例,并选取平均年龄相近的60例正常人作为对照(组B)。A、B组均经行神经电图检查,握力测定和两点辨别觉测定,分析神经传导速度改变与感觉、运动功能减退程度的关系。结果:A、B两组患者均有不同程度的神经传导改变:在A组患者神经传导改变中,运动和感觉传导速度(MCV和SCV)轻度下降,运动和感觉电位波幅(CMAP和SNAP)轻度下降,潜伏期(ML)轻度延长;在B组患者神经传导中,运动和感觉传导速度(MCV和SCV)明显下降,运动和感觉电位波幅(CMAP和SNAP)明显下降,潜伏期明显延长。结论:腕管综合征患者不同的临床表现有不同程度的神经电图表现,因此神经电图对神经传导的测定结果对腕管综合征患者的病情有良好的评估价值,值得临床推广。     

Neuromuscular transmission in cultures of adult human and rodent skeletal muscle after innervation in vitro by fetal rodent spinal cord

Electrophysiologic analyses have been carried out on in vitro-coupled explants of fetal rodent spinal cord and adult skeletal muscle of human as well as rodent origin. The studies demonstrate that characteristic neuromuscular transmission can develop and be maintained in these unusual tissue combinations during long-term culture. After coupling periods of 2–7 weeks in vitro, selective stimulation of spinal cord evokes widespread coordinated contractions in the muscle tissue. Simultaneous microelectrode recordings of cord and muscle responses to local cord, or ventral root, stimuli show that muscle action potentials (and contractions) generally occur with latencies of several msec after onset of cord discharges. Similar temporal relations are often seen during spontaneous rhythmic discharges of the coupled cord and muscle tissues. Long series of repetitive discharges, at 2–5 sec intervals, may occur synchronously between these cord and muscle explants, in response to single cord (or dorsal-root ganglion) stimuli, and they may also appear spontaneously. d-Tubocurarine (1–10 μg/ml) selectively and reversibly blocks neuromuscular transmission in these cultures. Eserine accelerates recovery of normal function. Spontaneous repetitive fibrillations of many of the cultured muscle fibers are observed sporadically, and these contractions often continue unabated after block of neuromusclar transmission by d-tubocurarine. Many of the fibers which show asynchronous fibrillations are probably not innervated (as in denervated muscle in situ). In some cases, however, extracellular as well as intracellular recordings indicate that similar fibrillations may also occur in fibers which are clearly innervated. Repetitive cord and muscle discharges are greatly augmented after introduction of strychnine. Complex rhythmic oscillatory (ca. 10/sec) afterdischarges generated in strychninized cord explants lead to similarly patterned muscle discharges (and contractions), which may also occur, at, times, in normal medium.     

肌电图检查评估腕管综合征手术效果的临床分析

目的:探讨采用肌电图检查评估腕管综合征的手术治疗效果。方法:选取35例(患侧手共39侧)临床确诊为腕管综合征并接受腕管切开减压术治疗的患者,于手术前后分别行肌电图检查,应用正中神经传导检查和拇短展肌针极肌电图检查,分析患者手术前和手术后腕部正中神经功能的变化情况。结果:手术后,患者正中神经感觉传导潜伏期异常率(33%)、正中神经运动传导潜伏期异常率(36%)较手术前(72%、74%)明显下降(P0.05),正中神经感觉传导波幅(7.40±5.05)较手术前(4.86±3.60)显著降低(P0.001),拇短展肌静息状态下失神经电位的异常率(69%)、重收缩时募集电位异常率(13%)均较手术前(85%、26%)明显下降(P0.05)。患者手术前后正中神经感觉传导速度和运动传导速度对比差异无统计学意义(P0.05)。结论:腕管切开减压术可解除正中神经卡压状态,明显恢复正中神经功能,增强拇短展肌肌力,临床治疗效果好。肌电图检查可为腕管综合征患者手术治疗效果的评估提供客观的依据。     

Follow-up assessment of patients with Pure Neural Leprosy in a reference center in Rio de Janeiro—Brazil

IntroductionPure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature.ObjectiveThis paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT).MethodsFifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS.ResultsParesthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT.DiscussionThe classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients.     

Refinement of the "Silver syndrome locus" on chromosome 11q12-q14 in four families and exclusion of eight candidate genes

Silver syndrome is a rare variant of autosomal dominant complicated hereditary spastic paraparesis (HSP), in which spasticity of the lower limbs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. The disease locus has been mapped to chromosome 11q12-q14. We report four Austrian families presenting with the typical clinical features of Silver syndrome. Sixteen individuals were affected upon clinical and/or electrophysiological examination. Ten persons showed mild to severe spasticity of the lower limbs. Wasting of the small hand muscles was present in nine affected family members of whom three had also gait disturbance. Three further individuals were asymptomatic. Electrophysiological studies showed normal or slightly to moderately slowed motor nerve conduction velocities, reduced amplitudes and occasionally chronodispersion of compound motor action potentials. In one patient, conduction block was observed. Sensory nerve action potentials were usually normal. Molecular genetic studies demonstrate linkage to chromosome 11q12-q14. Haplotype analysis in affected individuals indicates a common ancestor in the four families. By recombination analysis in affected individuals the Silver syndrome candidate gene interval can be reduced from 13 to 5.9 cM and can now be placed between the markers D11S1765 and D11S987. By sequence analysis of affected individuals eight functional and positional candidate genes could be excluded. Our study confirms the existence of the Silver syndrome locus on chromosome 11q12-q14 and provides the first report of nerve conduction velocity studies in Silver syndrome, which demonstrate the presence of a peripheral predominantly motor neuropathy.     

Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.     

Primary Hyperparathyroidism is Associated With subclinical Peripheral Neural Alterations

ObjectiveSome case reports have suggested primary hyperparathyroidism (PHPT) and peripheral polyneuropathy (PPN) are associated; however, there are no reports of studies examining this possible relationship. The aim of this study was to evaluate peripheral nerve conduction in subjects with PHPT.MethodsThe study involved 17 patients with PHPT. Mean patient age was 60.5 ± 12.9 years, serum calcium concentration was 11.5 ± 1.0 mg/dL, and the serum parathyroid hormone (PTH) level was 315 ± 569 pg/dL. The control group comprised 17 individuals without PHPT. The mean age of controls was 60.8 ± 12.5 years and the serum calcium concentration was 9.8 ± 0.3 mg/dL. Motor and sensory nerve conduction was assessed by electroneurography (ENG).ResultsThe following ENG parameters differed significantly between the PHPT and control groups: right (R) sural sensory nerve action potential conduction velocity (52.7 ± 6.3 m/s versus 58.0 ± 8.0 m/s; P = .041); R median compound muscle action potential (CMAP) amplitude (7.4 ± 1.6 mV versus 8.9 ± 1.7 mV; P = .002); R median CMAP latency (4.3 ± 1.2 ms versus 3.6 ± 0.6 ms; P = .032); R tibial CMAP latency (4.2 ± 1.1 ms versus 3.3 ± 0.4 ms; P = .001). The neurological examination was normal in all patients.ConclusionOur data demonstrate an association between PHPT and peripheral neurological alterations, consistent with subclinical sensory-motor PPN. (Endocr Pract. 2013;19:219-225)     

Electrophysiological changes in diabetic neuropathy: from subclinical alterations to disabling abnormalities

Clinical spectrum of diabetic neuropathy is variable; it may be asymptomatic, but once established as polyneuropathy, it is irreversible and may finally be disabling. To estimate the prevalence of subclinical diabetic polyneuropathy in the UAE, we undertook a pilot study by means of nerve conduction study (NCS) of peroneal motor and sural sensory studies in 60 diabetics with no symptoms of neuropathy. Neurological examination revealed clinical abnormalities suggesting polyneuropathy in 26 patients, 43% of the patients. NCS revealed abnormal values in 63% of the whole patients. Abnormal NCS was confirmed in 88% of the positive sign group. As to the negative sign group 44% had abnormalities in NCS. Prolonged F-wave latency was seen in 29% in no sign group and in 66% of the patients with positive signs. We found close association between neurological deficit score and abnormalities in NCS. Among various parameter of systemic nerve conduction study in subclinical patients, prolonged F-wave latency seems the commonest abnormality suggesting morphological changes in subclinical diabetic nerve. Decrease in amplitude of compound sensory action potential of sural nerve is another earlier abnormality, which is, then, accompanied by a fall in motor amplitude of peroneal nerve in advanced patients. Recently, our own group of Hirosaki has demonstrated that somatosensory central conduction time (CCT) between the spinal cord entry time and the arrival time to the sensory cortex is prolonged in diabetics. This abnormality might be partly responsible for the irreversible sensory deficits of diabetic neuropathy.     

Drug-induced peripheral neuropathies.

Review of the various drugs in current clinical use showed that over 50 of them may cause a purely sensory or mixed sensorimotor neuropathy. These include antimicrobials, such as isoniazid, ethambutol, ethionamide, nitrofurantoin, and metronidazole; antineoplastic agents, particularly vinca alkaloids; cardiovascular drugs, such as perhexiline and hydrallazine; hypnotics and psychotropics, notable methaqualone; antirheumatics, such as gold, indomethacin, and chloroquine; anticonvulsants, particularly phenytoin; and other drugs, including disulfiram, calcium carbimide, and dapsone. Patients receiving drug treatment who complain of paraesthesie, pain, muscle cramps, or other abnormal sensations and those without symptoms who are receiving drugs that are known or suspected to be neurotoxic should undergo neurological examination and studies of motor and sensory nerve conduction. This will allow the incidence of drug-induced peripheral neuropathy to be determined more precisely.     

THE APPEARANCE OF ACETYLCHOLINESTERASE IN THE MYOTOME OF THE EMBRYONIC RABBIT : An Electron Microscope Cytochemical and Biochemical Study

Acetylcholinesterase (AChE) activity has been studied in the myoblast of skeletal muscle of the 9–13 day fetal rabbit. Cytochemical activity is present in the nuclear envelope and the endoplasmic reticulum, including its derivatives the subsurface reticulum and the sarcoplasmic reticulum. End product is also found in the Golgi complex of the more differentiated myoblasts. The formation of reticulum-bound acetylcholinesterase in the myoblast appears to be independent of nerve-muscle contact, since the enzyme is present before the outgrowth of the spinal nerve. The nerve lacks cytochemical end product until the myoblast is well differentiated. Possible mechanisms of spontaneous muscle contraction have been discussed. A second type of myotomal cell, which exhibits a poorly localized end product of AChE activity, has been described. The ready solubility of the enzyme or diffusibility of its end product suggests that the enzyme may be a lyoesterase. This cell may be the precursor of the morphologically undifferentiated cell which is closely apposed to the myotubes in later stages of skeletal muscle development. Biochemical studies show a significant increase in AChE activity in the dermomyotome by day 12, when many of the myoblasts are well differentiated and the second type of myotomal cell is prominent. Cytochemical studies have indicated that many of the cells in the sample lack reaction product of enzymic activity, whereas others are very active. Biochemical values, therefore, reflect the amount of enzyme in the dermomyotome as a whole, but give little information on the enzymic content of individual cells.     

The "all-or-none" law in skeletal muscle and nerve fibres

In 1905 the Cambridge physiologist Keith Lucas extended the "all-or-none" principle (introduced by H. P. Bowditch for the cardiac tissue) to skeletal muscle and nerve fibres. Nevertheless, in a short time it was clear that nerve fibres obey this law, but also that frequency of discharge is another relevant factor in the nervous conduction.     

Mechanical stretch increases CCN2/CTGF expression in anterior cruciate ligament-derived cells

Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient’s skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.     

Improved Neurological Outcome by Intramuscular Injection of Human Amniotic Fluid Derived Stem Cells in a Muscle Denervation Model

PurposeThe skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS) have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model.ResultsNT-3 (Neurotrophin 3), BDNF (Brain derived neurotrophic factor), CNTF (Ciliary neurotrophic factor), and GDNF (Glia cell line derived neurotrophic factor) were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index) and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology.ConclusionIntramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve regeneration in a long term nerve anastomosis model.     

千频交流电刺激在外周神经传导阻断中的作用

感觉、运动或自主神经系统的异常病理活动与疼痛和痉挛等多种神经机能障碍有关。千频交流电（kilohertz frequency alternating current，KHFAC）刺激是一种阻断异常病理活动在外周神经内传导的有效方法，它在缓解相关神经机能障碍方面具有临床应用潜力。KHFAC产生的神经传导阻断受千频信号波形和参数、阻断电极设置和位置以及神经纤维类型和直径等因素影响，具有快速性、可控性、可逆性、局部作用和副作用小的特点。但是，在产生完全传导阻断前，KHFAC首先在靶向神经上激活一簇高频初始放电，这种初始响应可能导致肌肉抽搐或疼痛感。同时，在撤去KHFAC后处于阻断状态的靶向神经需要经历一段时间才能恢复正常传导能力，这是该技术导致的后续效应。目前，关于KHFAC阻断神经传导的生物物理机制假说包括千频信号诱发K⁺通道激活和Na⁺通道失活。本文首先介绍了KHFAC技术的电生理实验研究方法和计算模型仿真方法，然后综述目前关于KHFAC作用下神经传导阻断的研究进展，重点论述初始响应特性及消除方法、传导阻断的后续效应、刺激波形和参数的影响、电极设置与位置的影响以及该技术潜在的临床应用，同时归纳KHFAC阻断神经传导的生物物理机制，最后对该技术未来的相关研究进行展望。     

Axillary artery injury combined with delayed brachial plexus palsy due to compressive hematoma in a young patient: a case report

Aim

To prove the possibility of axillary nerve conduction changes following shoulder subluxation due to hemiplegia, in order to investigate the usefulness of screening nerve conduction studies in patients with hemiplegia for finding peripheral neuropathy.

Methods

Forty-four shoulders of twenty-two patients with a first-time stroke having flaccid hemiplegia were tested, 43 ± 12 days after stroke onset. Wasting and weakness of the deltoid were present in the involved side. Motor nerve conduction latency and compound muscle action potential (CMAP) amplitude were measured along the axillary nerve, comparing the paralyzed to the sound shoulder. The stimulation was done at the Erb's point whilst the recording needle electrode was inserted into the deltoid muscle 4 cm directly beneath the lateral border of the acromion. Wilcoxon signed rank test was used to compare the motor conduction between the sound and the paralytic shoulder. Mann-Whitney test was used to compare between plegic and sound shoulder in each side.

Results

Mean motor nerve conduction latency time to the deltoid muscle was 8.49, SD 4.36 ms in the paralyzed shoulder and 5.17, SD 1.35 ms in the sound shoulder (p < 0.001). Mean compound muscle action potential (CMAP) amplitude was 2.83, SD 2.50 mV in the paralyzed shoulder and was 7.44, SD 5.47 mV in the sound shoulder (p < 0.001). Patients with right paralyzed shoulder compared to patients with right sound shoulder (p < 0.001, 1-sided for latency; p = 0.003, 1-sided for amplitude), and patients with left paralyzed shoulder compared to patients with left sound shoulder (p = 0.011, 1-sided for latency, p = 0.001, 1-sided for amplitude), support the same outcomes. The electro-physiological changes in the axillary nerve may appear during the first six weeks after stroke breakout.

Conclusion

Continuous traction of the axillary nerve, as in hypotonic shoulder, may affect the electro-physiological properties of the nerve. It most probably results from subluxation of the head of the humerus, causing demyelinization and even axonopathy. Slowing of the conduction velocities of the axillary nerve in the paralyzed shoulders may be related also to the lowering of the skin temperature and muscular atrophy in the same limb. The usefulness of routine screening nerve conduction studies in the shoulder of hemiplegic patients seems to be advocated.     

Comparison of clinical findings and electromyography results in patients with preliminary diagnosis of carpal tunnel syndrome

ObjectiveTo evaluate the link between EMG findings and clinical status, the Boston questionnaire and the severity of pain in patients with pre-diagnosis of carpal tunnel syndrome.MethodsA total of 85 patients (133 hands) who presented to the Physical Therapy and Rehabilitation outpatient clinic consecutively with complaints of numbness, tingling, pain and weakness in their hands were evaluated for their demographic and clinical features. After the initial evaluation, the diagnosis of CTS was confirmed by EMG. Visual analog scale (VAS), the Boston Questionnaire (Symptom Severity Scale = SSS, Functional Status Scale = FSS) and nerve conduction study results (sensory conduction velocity = SCV, distal motor latency = DML, compound muscle action potential = CMAP) were enrolled.ResultsEighty-five patients (58 female and 27 male) participated in this study yielding 133 hands (73 right hands, 60 right hands) with CTS. The mean age was 48.3 ± 10.41 years. Of all patients, 68.2 % were female and 31.8 % were male. A statistically significant relationship was found between SSS and duration of symptoms, VAS, both right and left SCV, DML and CMAP. A statistically significant relationship was found between FSS and duration of symptoms, VAS and only right SCV, DML and CMAP.ConclusionThe diagnosis of CTS should be evaluated not only as an electrodiagnostic finding, but also the clinical picture of the patients. According to our results, both SSS and FSS had good correlations with VAS and the findings of EMG. Therefore, the Boston Questionnaire can provide a standardized measure of symptom severity and functional status in patients with CTS.     

Factors underlying the early limb muscle weakness in acute quadriplegic myopathy using an experimental ICU porcine model

The basic mechanisms underlying acquired generalized muscle weakness and paralysis in critically ill patients remain poorly understood and may be related to prolonged mechanical ventilation/immobilization (MV) or to other triggering factors such as sepsis, systemic corticosteroid (CS) treatment and administration of neuromuscular blocking agents (NMBA). The present study aims at exploring the relative importance of these factors by using a unique porcine model. Piglets were all exposed to MV together with different combinations of endotoxin-induced sepsis, CS and NMBA for five days. Peroneal motor nerve conduction velocity and amplitude of the compound muscle action potential (CMAP) as well as biceps femoris muscle biopsy specimens were obtained immediately after anesthesia on the first day and at the end of the 5-day experimental period. Results showed that peroneal nerve motor conduction velocity is unaffected whereas the size of the CMAP decreases independently of the type of intervention, in all groups after 5 days. Otherwise, despite a preserved size, muscle fibre specific force (maximum force normalized to cross-sectional area) decreased dramatically for animals exposed to MV in combination with CS or/and sepsis. These results suggest that the rapid declines in CMAP amplitude and in force generation capacity are triggered by independent mechanisms with significant clinical and therapeutic implications.     

Secondary carpal tunnel surgery

A small but significant group of patients with carpal tunnel syndrome "fail" primary carpal tunnel release and require secondary surgery. The persistence or recurrence of previous symptoms or the development of new symptoms is often indicative of the nature of the patient's problem. Postoperative complications may be classified into the general areas of neurological, vascular, tendon, and wrist complaints. A thorough clinical evaluation, including a complete neurological examination of the hand and upper extremity, provides an accurate assessment of the status of the median nerve. Important surgical techniques that may be used during secondary carpal tunnel surgery include internal neurolysis, neuroma-in-continuity assessment, neuroma management, nerve grafting, and tissue interposition flaps.     

Functional evaluation of nerve-skeletal muscle constructs engineered in vitro

Summary Previously, we have engineered three-dimensional (3-D) skeletal muscle constructs that generate force and display a myosin heavy-chain (MHC) composition of fetal muscle. The purpose of this study was to evaluate the functional characteristics of 3-D skeletal muscle constructs cocultured with fetal nerve explants. We hypothesized that coculture of muscle constructs with neural cells would produce constructs with increased force and adult MHC isoforms. Following introduction of embryonic spinal cord explants to a layer of confluent muscle cells, the neural tissue integrated with the cultured muscle cells to form 3-D muscle constructs with extensions. Immunohistochemical labeling indicated that the extensions were neural tissue and that the junctions between the nerve extensions and the muscle constructs contained clusters of acetylcholine receptors. Compared to muscles cultured without nerve explants, constructs formed from nerve-muscle coculture showed spontaneous contractions with an increase in frequency and force. Upon field stimulation, both twitch (2-fold) and tetanus (1.7-fold) were greater in the nerve-muscle coculture system. Contractions could be elicited by electrically stimulating the neural extensions, although smaller forces are produced than with field stimulation. Severing the extension eliminated the response to electrical stimulation, excluding field stimulation, as a contributing factor. Nervemuscle constructs showed a tendency to have higher contents of adult and lower contents of fetal MHC isoforms, but the differences were not significant. In conclusion, we have successfully engineered a 3-D nerve-muscle construct that displays functional neuromuscular junctions and can be electrically stimulated to contract via the neural extensions projecting from the construct.