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Study Design: Controlled radiological study., Objective: Ascertain if a difference exists in the mechanical effects on the cord between the unilateral and bilateral straight leg raise (SLR) and to verify whether the effect on the spinal cord may be cumulative between the two., Summary of Background Data: To the authors' knowledge these are the first data on noninvasive, in vivo, normative measurement of spinal cord displacement with bilateral SLR test., Methods: Sixteen asymptomatic volunteers were scanned with 1.5-T magnetic resonance scanner (Siemens Avanto, Erlangen, Germany) using T2-weighted turbo spin-echo fat-saturation sequence. The displacement of the medullar cone relative to the vertebral endplate of the adjacent vertebra during the passive bilateral SLR was quantified and compared with the position of the conus in the neutral (anatomic) position and with unilateral SLR. Each movement was performed twice for evaluation of reproducibility. The measurements were repeated by 2 observers. Four practitioners performed the maneuvers in a random sequence to avoid series effects., Results: Compared with the neutral (anatomic) position, the medullar cone displaced caudally in the spinal canal by 2.33 ± 1.2 mm (μ ± SD) with unilateral (P ≤ 0.001) and 4.58 ± 1.48 mm with bilateral SLR (P ≤ 0.001). Statistical significance was also reached for bilateral versus unilateral SLR (P ≤ 0.001). Spearman correlations proved higher than 0.99 for intra and interobserver reliability, and 0.984 for results reproducibility in bilateral SLR., Conclusion: The caudal displacement of the medullar cone was significantly greater (almost double) with the bilateral SLR than the unilateral SLR. We hypothesize that this greater movement may be because more force was transmitted to the cord through a larger number nerve roots with the bilateral than unilateral SLR. The high correlation values in this study show that these movements are consistent and reproducible. This study offers baseline measurements on which further studies in diagnosis and treatment of lumbar disc protrusion and radiculopathy may be developed.

Study Design: Controlled radiological study., Objective: To investigate noninvasively in vivo spinal cord displacement in the vertebral canal during the passive straight leg raise (SLR) in asymptomatic subjects. The basic assumption is that the cord follows L5 and S1 nerve roots displacement by similar magnitude and direction (principle of linear dependence)., Summary of Background Data: It is generally accepted that the SLR produces some caudal movement mainly of L5 and S1 nerve roots, but the magnitude of this displacement is still a matter of debate., Methods: Sixteen asymptomatic volunteers were scanned with 1.5-T magnetic resonance scanner (Siemens Avanto, Erlangen, Germany) using T2-weighted turbo spin-echo fat-saturation sequence. The displacement of the medullar cone relative to the vertebral endplate of the adjacent vertebra during the passive SLR was quantified and compared with the position of the conus in the neutral (anatomic) position. Each movement was performed twice for evaluation of reproducibility. The measurements were repeated by 2 observers. Four practitioners performed the maneuvers in a random sequence to avoid series effects., Results: Compared with the neutral (anatomic) position, the medullar cone displaced caudally in the spinal canal by 2.31 ± 1.2 mm with right (P ≤ 0.001) and 2.35 ± 1.2 mm with left SLR (P ≤ 0.001). Spearman correlations proved higher than 0.99 for intra and interobserver reliability, as well as results reproducibility testing for each maneuver., Conclusion: The data show that the spinal cord in the thoracolumbar region slides distally in response to the clinically applied SLR test. The high correlation values in this study show that these movements are consistent and reproducible. Because of the neural continuum, the authors speculate that this movement might be directly proportional to the sliding of the L5 and S1 neural roots. This study offers baseline measurements on which further studies in diagnosis of lumbar disc protrusion and radiculopathy may be developed.

Study Design: A prospective study., Objective: To examine the diameter (mm), transverse diameter (mm), and cross-sectional area (mm²) of the C5, C6, and C7 nerve roots using ultrasonography., Summary of Background Data: Each of the cervical nerve roots affected a different motor or sensory area. Although there were several studies that performed a detailed assessment of cervical nerve root anatomy in cadavers, only a few studies on the thickness of cervical nerve roots in living specimens have been performed. We examined whether the thickness of the C5, C6, and C7 nerve roots, as well as the area supplied by each of the roots, varied., Methods: All 219 subjects (99 males and 120 females; mean age, 47 ± 15 yr) were healthy volunteers. The diameter and the transverse diameter were measured via ultrasonography, and the cross-sectional area was calculated for each of the C5-C7 nerve roots., Results: The following diameter measurements (right and left, respectively) were obtained: C5, 2.8 and 2.9 mm; C6, 3.6 and 3.8 mm; and C7, 3.3 and 3.4 mm. The following transverse diameter measurements were obtained (right and left, respectively): C5, 2.8 and 3.0 mm; C6, 3.7 and 3.8 mm; and C7, 3.5 and 3.4 mm. The following cross-sectional area measurements (right and left, respectively) were obtained: C5, 6.3 and 6.4 mm²; C6, 10.7 and 11.0 mm²; and C7, 8.8 and 8.8 mm². Based on the 3 measurement methods, the C5 nerve root was significantly thinner than the other 2 nerve roots (P < 0.001), and the C7 nerve root was smaller than the C6 nerve root (P = 0.001)., Conclusion: The C5 nerve root was significantly thinner than the C6 and C7 cervical nerve roots. The fact that the C5 nerve is thinner may render it more susceptible to damage during cervical surgery.

The aim of this study was to evaluate the effects of electrophysiological monitoring on selective rhizotomy of the glossopharyngeal nerve (SRGN) in treatment of glossopharyngeal neuralgia (GPN). From December, 2009 to May, 2012, SRGN was carried out on 8 patients with GPN, through a suboccipital sigmoid sinus posterior approach. The electrodes were placed on the cricothyroid muscle (vagus nerve). Two groups of amplitudes (A1 and A2) were recorded. A1 was recorded when the mixed nerve root was stimulated, and A2 when the part of the vagus nerve was stimulated. The glossopharyngeal nerve was sectioned and the vagus nerve was preserved. If A1/A2 < 50%, the mixed nerve root should be sectioned, otherwise the mixed nerve root should be retained. As the representation of vagus nerve, the averages of A1 and A2 were 22 and 36 μV respectively. The 8 patients were followed up for 9-39 months. Seven patients (87.5%) obtained complete pain relief (excellent) without complications such as hoarseness, dysphagia, and cough. One case (12.5%) obtained moderate relief (good), and was under control with carbamazepine at a dosage of 600 mg/d. Cough was occurred in this patient, but relieved in two months. Electrophysiological monitoring in SRGN can improve the efficiency of pain relief and reduce the incidence of complications., (Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background Context: The correction of severe spinal deformities by an isolated posterior approach often involves cord manipulation together with hypotensive anesthesia. To date, the efficiency of methods to increase the tolerance of the cord to displacement and the influence of hypotension on this tolerance is yet to be assessed., Purpose: The objective of this study was to determine the limits of cord displacement before the disappearance of neurophysiologic signals. The influence of the type of force applied, the section of the roots, and the induced hypotension on the cord's tolerance to displacement was also assessed., Study Design: Experimental study using a domestic pig model., Outcome Measures: Successive records of cord-to-cord motor evoked potentials were obtained during displacement maneuvers. Displacing forces were released immediately after the absence of neurophysiologic signals., Methods: Surgical procedures were performed under conventional general anesthesia. The spinal cord and nerve roots from T6 to T10 levels were exposed by excision of the posterior elements, allowing for free cord movement. Three groups were established according to the method of spinal cord displacement: the separation (Group 1, n=5), the root stump pull (Group 2, n=5), and the torsion groups (Group 3, n=5). An electromechanical external device was used to apply the displacing forces. The three displacement tests were repeated after sectioning the adjacent nerve roots. The experiments were first carried out under normotension and afterward under induced hypotension., Results: In Group 1, evoked potential disappeared with a displacement of 10.1±1.6 mm with unharmed roots and 15.3±4.7 mm after the sectioning of four adjacent roots (p<.01). After induced hypotension, potentials were lost at 4.0±1.2 mm (p<.01). In Group 2, the absence of potentials occurred at 20.0±4.3 mm and increased to 23.5±2.1 mm (p<.05) after cutting the two contralateral roots. Under hypotensive conditions, the loss of neurophysiologic signals was detected at 5.3±1.2 mm (p<.01). In Group 3, the cord allowed torsion of 95.3±.2° that increased to 112.4±7.1° if the contralateral roots were cut. Under hypotension, the loss of potentials was found at 20±6.2° (p<.01)., Conclusions: In this experimental model, it was possible to displace the thoracic spinal cord by a distance superior to the spinal cord width without suffering neurophysiologic changes. The limits of cord displacement increase when the adjacent nerve roots are sacrificed. Induced hypotension had a dramatic effect on the tolerance of the spinal cord for displacement. This work has an important clinical significance because induced hypotension during specific spine surgery procedures requiring spinal cord manipulation in humans may increase the risk of neurologic spinal cord injury., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: Information regarding the selection procedure for selective dorsal rhizotomy (SDR) in children with spastic cerebral palsy (CP) is scarce. Therefore, the aim of this study was to summarize the selection criteria for SDR in children with spastic CP., Method: A systematic review was carried out using the following databases: MEDLINE, CINAHL, EMBASE, PEDro, and the Cochrane Library. Additional studies were identified in the reference lists. Search terms included 'selective dorsal rhizotomy', 'functional posterior rhizotomy', 'selective posterior rhizotomy', and 'cerebral palsy'. Studies were selected if they studied mainly children (<18y of age) with spastic CP, if they had an intervention of SDR, if they had a detailed description of the selection criteria, and if they were in English. The levels of evidence, conduct of studies, and selection criteria for SDR were scored., Results: Fifty-two studies were included. Selection criteria were reported in 16 International Classification of Functioning, Disability and Health model domains including 'body structure and function' (details concerning spasticity [94%], other movement abnormalities [62%], and strength [54%]), 'activity' (gross motor function [27%]), and 'personal and environmental factors' (age [44%], diagnosis [50%], motivation [31%], previous surgery [21%], and follow-up therapy [31%]). Most selection criteria were not based on standardized measurements., Interpretation: Selection criteria for SDR vary considerably. Future studies should describe clearly the selection procedure. International meetings of experts should develop more uniform consensus guidelines, which could form the basis for selecting candidates for SDR., (© 2013 Mac Keith Press.)

Presynaptic inhibition is one of the most powerful inhibitory mechanisms in the spinal cord. The underlying physiological mechanism is a depolarization of primary afferent fibers mediated by GABAergic axo-axonal synapses (primary afferent depolarization). The strength of primary afferent depolarization can be measured by recording of volume-conducted potentials at the dorsal root (dorsal root potentials, DRP). Pathological changes of presynaptic inhibition are crucial in the abnormal central processing of certain pain conditions and in some disorders of motor hyperexcitability. Here, we describe a method of recording DRP in vivo in mice. The preparation of spinal cord dorsal roots in the anesthetized animal and the recording procedure using suction electrodes are explained. This method allows measuring GABAergic DRP and thereby estimating spinal presynaptic inhibition in the living mouse. In combination with transgenic mouse models, DRP recording may serve as a powerful tool to investigate disease-associated spinal pathophysiology. In vivo recording has several advantages compared to ex vivo isolated spinal cord preparations, e.g. the possibility of simultaneous recording or manipulation of supraspinal networks and induction of DRP by stimulation of peripheral nerves.

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits.

Increased dietary salt in rats has been shown to sensitize central sympathetic circuits and enhance sympathetic responses to several stressors, including hyperinsulinemia, intracerebroventricular injection of angiotensin, and electrical stimulation of sciatic nerve afferents. These findings prompted us to test the hypothesis that increased dietary salt enhanced the exercise pressor reflex. Male Sprague-Dawley rats were fed 0.1% (low) or 4.0% (high) NaCl chow for 2 to 3 wk. On the day of the experiment, the rats were decerebrated, and the hind limb muscles were statically contracted for 30 s by electrically stimulating the cut peripheral ends of the L4 and L5 ventral roots. We found that contraction produced a significantly greater increase in mean arterial pressure of rats fed 4.0% (n = 26) vs. 0.1% (n = 22) NaCl (24 ± 2 vs. 15 ± 2 mmHg, respectively; P < 0.05). Baseline mean arterial pressure was not different between groups (0.1%, 77 ± 4 vs. 4.0% NaCl, 80 ± 3 mmHg). Likewise, the tension time indexes were not different between the two groups (P = 0.42). Section of the L4 and L5 dorsal roots greatly attenuated both the pressor and cardioaccelerator responses to contraction in both groups of rats, an effect showing that the responses were reflex in origin. Finally, electrical stimulation of the lumbar sympathetic chain produced similar increases in mean arterial pressure and decreases in femoral arterial blood flow and conductance between rats fed 0.1% vs. 4.0% NaCl diets. We conclude that increased dietary salt enhances the exercise pressor reflex.

Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in the microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu(31), Pro(34)]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked the detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu(31), Pro(34)]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu(31), Pro(34)]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [(35)S]GTPγS binding simulated by [Leu(31), Pro(34)]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating the inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Introduction: In this study we used a rat model to elucidate the linear make-up of each major nerve of the upper limb by the C7 root through sensory stimulation and functional magnetic resonance imaging (fMRI)., Methods: The C7 nerve root and major nerves of the right forelimb were stimulated electrically. Blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) was performed concurrently. Voxel overlap within the primary sensory cortex was calculated., Results: C7 comprised sensation in <1% in the musculocutaneous nerve, 6% in the ulnar nerve, 16% in the radial nerve, and 19% in the median nerve (P<0.005 for each). The overlap was always <25% for each major nerve., Conclusions: This study helps explain why C7 is a suitable donor for brachial plexus injury treatment and why there is only a transient sensory deficit after transfer.

Primary sensory axon injury is common after spinal cord and root injuries and causes patients to suffer chronic pain and persistent loss of sensation and motor coordination. The devastating consequences of such injuries are due primarily to the failure of severed axons to regenerate within the damaged CNS. Our understanding of the molecular and cellular events that play key roles in preventing or promoting functional regeneration is far from complete, in part because complex and dynamic changes associated with nerve injury have had to be deduced from comparisons of static images obtained from multiple animals after their death. Revolutionary innovations in optics and mouse transgenics now permit real-time monitoring of regenerating dorsal root axons directly in living animals. Here, we describe detailed procedures for repetitive monitoring of identified axons in a lumbar dorsal root over hours to weeks using both widefield and two-photon microscopes. We also discuss the strengths and limitations of in vivo imaging and provide suggestions based on our own experience for troubleshooting issues associated with repeated anesthetization, an extensive laminectomy, and post-op care. These techniques provide the unprecedented opportunity to obtain novel insights into why sensory axons fail to reenter the spinal cord.

Skilled motor control is regulated by the convergence of somatic sensory and motor signals in brain and spinal motor circuits. Cervical deafferentation is known to diminish forelimb somatic sensory representations rapidly and to impair forelimb movements. Our focus was to determine what effect deafferentation has on the motor representations in motor cortex, knowledge of which could provide new insights into the locus of impairment following somatic sensory loss, such as after spinal cord injury or stroke. We hypothesized that somatic sensory information is important for cortical motor map topography. To investigate this we unilaterally transected the dorsal rootlets in adult rats from C4 to C8 and mapped the forelimb motor representations using intracortical microstimulation, immediately after rhizotomy and following a 2-week recovery period. Immediately after deafferentation we found that the size of the distal representation was reduced. However, despite this loss of input there were no changes in motor threshold. Two weeks after deafferentation, animals showed a further distal representation reduction, an expansion of the elbow representation, and a small elevation in distal movement threshold. These changes were specific to the forelimb map in the hemisphere contralateral to deafferentation; there were no changes in the hindlimb or intact-side forelimb representations. Degradation of the contralateral distal forelimb representation probably contributes to the motor control deficits after deafferentation. We propose that somatic sensory inputs are essential for the maintenance of the forelimb motor map in motor cortex and should be considered when rehabilitating patients with peripheral or spinal cord injuries or after stroke., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Hoffmann reflex to tibial nerve stimulation at the popliteal fossa (tibial H-reflex) is routinely used to evaluate S1 radiculopathy. However, it lacks sensitivity because other lesions along this reflex circuit affect the H-reflex bilaterally. This study was undertaken to determine whether the H-reflex evoked by stimulating proximally at the S1 foramen (S1 foramen H-reflex) could improve S1 root lesion evaluation sensitivity in patients with diabetes mellitus. A randomized paired study was designed to evaluate tibial and S1 foramen H-reflexes; bilateral H-M interval (HMI) and H-reflex latency were compared in 22 diabetic patients with unilateral S1 radiculopathy. Other electrophysiological evaluations included standard tibial conduction studies, sural conduction studies and needle electromyography (EMG). The S1 foramen H-reflex had a significantly higher sensitivity (91.0%, 20 of 22) in evaluating S1 radiculopathy than the conventional tibial H-reflex (63.6%, 14 of 22, p < 0.05). Bilateral tibial compound muscle action potential amplitudes were reduced in 3 patients, and sural sensory nerve action potential amplitudes decreased in 7 patients. Needle EMG revealed denervation restricted to the paraspinal muscle and myotomes supplied by the S1 nerve root on the ipsilateral side in 18 patients, and multiple lumbosacral nerve roots were involved bilaterally in the other 4 patients. Our results demonstrate that the S1 foramen H-reflex is a more sensitive assessment of S1 compressive radiculopathy in patients with diabetes mellitus.

Objective: To generate peripheral nerve animal model of pure motor nerve fibers/pure sensory nerve fibers, and identify them., Methods: The SPF SD rats were adopted in this study, and divided into 3 groups. In group A, we ablated L2-L4 ventral roots (VRs) to generate peripheral nerve animal model of pure sensory fibers. In group B, we ablated L2-L4 dorsal root ganglions (DRGs) to generate peripheral nerve animal model of pure motor fibers. Two time end-points were set as 2 weeks and 4 weeks. Neuron cells in lumbar spinal cords were detected by immunohistochemical staining with antibody of neuronal nuclei (NeuN). Motor neuron cells in lumbar spinal cords of pure motor fiber animal models and sensory neuron cells in lumbar spinal cords of pure sensory fiber animal models were counted respectively, and then compared to that of normal animals. Femoral nerves distal to the furcation were stained in osmium tetroxide, and then myelinated nerve fibers in the muscle branch and cutaneous branch of femoral nerve were counted respectively., Results: The mean numbers of sensory neuron cells and motor neuron cells in normal lumbar spinal cords were 62.57 ± 1.02 and 29.73 ± 3.03 per 10 × 20 visual field respectively. For different end-points, the mean numbers of sensory neuron cells after ablating vental foots were 62.12 ± 1.77 (2 weeks), 62.15 ± 1.32 (4 weeks) per 10 × 20 visual field respectively; the mean numbers of motor neuron cells after ablating DRGs were 30.12 ± 0.44 (2 weeks), 30.00 ± 1.87 (4 weeks) per 10 × 20 visual field respectively. In group A, motor axons in muscle branch were degenerated as the sensory axons in muscle branch and cutaneous branch were not changed. The senory axons in femoral nerve for the two end-points were 1 558.17 ± 50.14 (2 weeks) and 1 544.00 ± 47.42 (4 weeks). In group B, sensory axons in muscle branch were degenerated as the motor axons were reserved. The motor axons in muscle branch for the two end-points were 387.67 ± 48.50 (2 weeks) and 393.50 ± 27.86 (4 weeks). There was no statistically significant difference in these mean numbers for the two end-points. The degenerating axons and myelin sheath had not been totally eliminated by the endpoint of 2 weeks., Conclusion: Peripheral nerve animal model of pure motor fibers can be generated by ablating L2-L4 DRGs; peripheral nerve animal model of pure sensory fibers can be generated by ablating L2-L4 ventral roots. The degenerating axons and myelin sheath have been totally eliminated by the end-point of 4 weeks. Ablating the ventral roots does not influence the survival of sensory neuron cells; and ablating the DRGs does not influence the survival of motor neuron cells.

Compression of spinal roots is an important medical problem, which may arise from intervertebral disc herniation, tumor growth or as a result of high energy accidents. Differently from avulsion, root crushing maintains the central/peripheral nervous system (CNS/PNS) connection, although the axons are axotomized and motoneurons degenerate. Such neuronal death may decrease and delay motor function recovery. In the present study we have investigated the neuroprotective effects of mesenchymal stem cell (MSC) therapy following such proximal lesions. Motor recovery and synaptic stabilization were analyzed by the use of morphological and functional approaches. For that, crushing the ventral roots at L4, L5 and L6 was unilaterally performed in Lewis rats. Four weeks after injury, an increased motoneuron survival was observed in the MSC-treated group, coupled with a smaller decrease of inputs at the motoneuron surface and nearby neuropil, seen by synaptophysin and synapsin immunolabeling and decreased astrogliosis, seen by GFAP immunolabeling. In this sense, MSC-treated group displayed a significant preservation of GABAergic terminals, indicating a possible neuroprotection to glutamate excitotoxicity. Motor function recovery was acutely improved in MSC-treated group as compared to Dulbeco's modified eagle medium (DMEM)-treated. Overall, we provide evidence that ventral root crushing (VRC), although milder than avulsion, results in significant loss of motoneurons (~51%) that can be reduced by MSC administration within the spinal cord. Such treatment also improves the number of synapses immunoreactive against molecules present in inhibitory inputs. Also, an increased number of regenerated axons was obtained in the MSC-treated group, in comparison to the DMEM-treated control. Overall, MSC therapy acutely improved limb strength and gait coordination, indicating a possible clinical application of such treatment following proximal lesions at the CNS/PNS interface., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Urinary disorders account for 10% of deaths in patients with complete spinal cord injury. Sacral anterior root stimulation (SARS) may be a valuable therapeutic option to restore complete and voluntary micturition (CVM), but questions on its cost-effectiveness remain., Objective: To evaluate the cost-effectiveness of SARS to restore CVM in patients with complete spinal cord injury., Methods: We conducted a nonrandomized, multicenter, parallel-group cohort study comparing SARS vs. current medical treatments with catheterization or reflex micturition. CVM was assessed at 12 months (end of follow-up) by urodynamic examination. Medical and nonmedical costs were measured in the perspective of the French national health insurance. Linear regression models were used to estimate the incremental net benefit ((Equation is included in full-text article.); λ = willingness-to-pay) adjusted for potential confounders, and P (INB >0) (i.e., probability of SARS being cost-effective vs medical treatment) for different values of λ., Results: Twenty-five patients were included in each group in 2005 to 2009. At inclusion, mean age was 41 years; 45 (90%) patients were male, and 29 (59%) patients were paraplegic. At 12 months, 15 (60%) patients with SARS had a CVM vs. 3 (12%) patients with medical treatment (P < .001). The total mean cost was 42,803 €; and 8762 €, respectively (P < .001). After adjustment for CVM and voiding methods at inclusion, P (INB >0) was 74% at λ = 100,000 €. This probability was 94% in a sensitivity analysis excluding 6 patients presenting a CVM at inclusion., Conclusion: The effectiveness and cost of SARS are much higher than for medical treatment. Our results inform decision makers of the opportunity to reimburse SARS in this vulnerable population.

Background: Neurosurgical residents have traditionally been instructed on surgical techniques and procedures through an apprenticeship model. Currently, there has been research and interest in expanding the neurosurgical education model., Objective: To establish a posterior cervical decompression educational curriculum with a novel cervical simulation model., Methods: The Congress of Neurological Surgeons developed a simulation committee to explore and develop simulation-based models. The educational curriculum was developed to have didactic and technical components with the incorporation of simulation models. Through numerous reiterations, a posterior cervical decompression model was developed and a 2-hour education curriculum was established., Results: Individual's level of training varied, with 5 postgraduate year (PGY) 2 participants, 1 PGY-3 participant, 2 PGY-5 participants, and 1 attending, with the majority being international participants (6 of 9, 67%). Didactic scores overall improved (7 of 9, 78%). The technical scores of all participants improved from 11 to 24 (mean, 14.1) to 19 to 25 (mean, 22.4). Overall, in the posterior cervical decompression simulator, there was a significant improvement in the didactic scores (P = .005) and the technical scores (P = .02)., Conclusion: The posterior cervical decompression simulation model appears to be a valuable tool in educating neurosurgery residents in the aspects of this procedure. The combination of a didactic and technical assessment is a useful teaching strategy in terms of educational development.

Background: Peripheral nerve (PN) transplantation and ventral root implantation are the two common types of recovery operations to restore the connection between motoneurons and their target muscles after brachial plexus injury. Despite experience accumulated over the past decade, fundamental knowledge is still lacking concerning the efficacy of the two microsurgical interventions., Methods: Thirty-eight adult female Sprague-Dawley rats were divided into 5 groups. Immediately following root avulsion, animals in the first group (n = 8) and the second group (n = 8) received PN graft and ventral root implantation respectively. The third group (n = 8) and the fourth group (n = 8) received PN graft and ventral root implantation respectively at one week after root avulsion. The fifth group received root avulsion only as control (n = 6). The survival and axonal regeneration of severed motoneurons were investigated at 6 weeks post-implantation., Results: Re-implantation of ventral roots, both immediately after root avulsion and in delay, significantly increased the survival and regeneration of motoneurons in the avulsed segment of the spinal cord as compared with PN graft transplantation., Conclusions: The ventral root re-implantation is a better surgical repairing procedure than PN graft transplantation for brachial plexus injury because of its easier manipulation for re-implanting avulsed ventral roots to the preferred site, less possibility of causing additional damage and better effects on motoneuron survival and axonal regeneration.

Magnetic stimulation can activate the human central and peripheral nervous systems non-invasively and virtually painlessly. Magnetic stimulation over the spinal enlargements can activate spinal nerves at the neuroforamina (magnetic-neuroforamina stimulation). This stimulation method provides us with information related to the latency of compound-muscle action potential (CMAP), which is usually interpreted as peripheral motor-conduction time (PMCT). However, this stimulation method has faced several problems in clinical applications. One is that supramaximal CMAPs were unobtainable. Another is that magnetic stimulation did not usually activate the spinal nerves in the spinal canal, i.e., the cauda equina, which prevented an evaluation of its conduction. For these reasons, magnetic-neuroforamina stimulation was rarely used to evaluate the conduction of peripheral nerves. It was mainly used to evaluate the conduction of the corticospinal tract using the parameter of central motor-conduction time (CMCT), which was calculated by subtracting PMCT from the latency of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex. Recently, supramaximal stimulation has been achieved in magnetic-neuroforamina stimulation, and this has contributed to the measurement of both CMAP size and latency. The achievement of supramaximal stimulation is ascribed to the increase in magnetic-stimulator output and a novel coil, the magnetic augmented translumbosacral stimulation (MATS) coil. The most proximal part of the cauda equina can be reliably activated using the MATS coil (magnetic-conus stimulation), thus contributing to the measurement of cauda equina conduction time (CECT) and cortico-conus motor-conduction time (CCCT). These recent developments in magnetic-motor-root stimulation enable us to more precisely evaluate the conduction of the proximal part of peripheral nerves and that of the corticospinal tract for lower-limb muscles. In this review article, we summarise the basic mechanisms, recent topics, clinical applications, comparison to electrical stimulation, pitfalls, safety and additional issues in magnetic-motor-root stimulation., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Rare cases of demyelinating neuropathy have been described in association with amyotrophic lateral sclerosis (ALS). We report two patients with typical ALS whose initial electroneuromyographic (ENMG) presentation could suggest the existence of a process of motor nerve fiber demyelination. However, subsequent ENMG examinations and the fatal course of the disease in a few months rather supported severe ongoing axonal degeneration at the origin of motor nerve conduction abnormalities. Repeated examinations could be required to distinguish between ENMG features of concomitant demyelinating neuropathy and rapidly progressive motor neuron loss in ALS., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Sensory feedback is critical for normal locomotion and adaptation to external perturbations during movement. Feedback provided by group Ia afferents influences motor output both directly through monosynaptic connections and indirectly through spinal interneuronal circuits. For example, the circuit responsible for reciprocal inhibition, which acts to prevent co-contraction of antagonist flexor and extensor muscles, is driven by Ia afferent feedback. Additionally, circuits mediating presynaptic inhibition can limit Ia afferent synaptic transmission onto central neuronal targets in a task-specific manner. These circuits can also be activated by stimulation of proprioceptive afferents. Rodent locomotion rapidly matures during postnatal development; therefore, we assayed the functional status of reciprocal and presynaptic inhibitory circuits of mice at birth and compared responses with observations made after 1 wk of postnatal development. Using extracellular physiological techniques from isolated and hemisected spinal cord preparations, we demonstrate that Ia afferent-evoked reciprocal inhibition is as effective at blocking antagonist motor neuron activation at birth as at 1 wk postnatally. In contrast, at birth conditioning stimulation of muscle nerve afferents failed to evoke presynaptic inhibition sufficient to block functional transmission at synapses between Ia afferents and motor neurons, even though dorsal root potentials could be evoked by stimulating the neighboring dorsal root. Presynaptic inhibition at this synapse was readily observed, however, at the end of the first postnatal week. These results indicate Ia afferent feedback from the periphery to central spinal circuits is only weakly gated at birth, which may provide enhanced sensitivity to peripheral feedback during early postnatal experiences.

Objective: To verify the safety and clinical use of non-invasive high-voltage electrical stimulation (HVES) in patients with compressive radiculopathy. To test the feasibility of HVES to survey nerve root function during lumbosacral surgery., Methods: In 20 patients undergoing lumbosacral surgery for degenerative spinal diseases, compound muscle action potentials (CMAPs) evoked by maximal HVES were bilaterally recorded throughout surgery from L3 to S2 radicular territories. A preliminary study was performed in awake patients to rule out detrimental effects caused by HVES., Results: Preoperative study confirmed the safety of HVES. Unexpectedly, a transient but significant remission of pain was observed after root stimulation. Intraoperative monitoring (IOM) was accomplished in all patients. HVES never hindered surgical procedures and never caused mechanical damage within the operatory field. In 4 patients acute, highly focal and reversible conduction failure was promptly detected by HVES in radicular territories congruent with the root manipulated at that moment., Conclusions: HVES is a safe and sensitive tool to monitor nerve root function in lumbosacral surgery., Significance: The method is based on the assumption that any acute conduction failure occurring during surgery can be immediately and unambiguously detected by HVES if root stimulation is supramaximal and delivered rostral to the surgical level., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

In the present study, we characterized the evoked electrical activity from T(13) to S(2) dorsal roots (DRs) during glass probe-stimulation of the vagina-cervix-uterus junction (VCUJ) of female Wistar rats. The results showed that gentle stimulation of VCUJ evoked high-amplitude electrical activity in L(3) and L(6) DRs. Hypogastric or pelvic nerve transection failed to abolish this activity. L(6)-S(1) spinal trunk transection abolished the high-amplitude electrical activity evoked in L(6) DR, while transection of the lumbosacral trunk blocked the high-amplitude electrical activity evoked in L(3) DR. These data suggest that during copulation, penile intromission likely activates the low-threshold sensory receptors of the VCUJ, thereby evoking sensory neural activity that enters the spinal cord via L(3) and L(6) dorsal roots, whose axons travel through the lumbosacral trunk and pudendal nerve., (Copyright © 2013. Published by Elsevier B.V.)

Electrode mounts are being developed to improve electrical stimulation and recording. Some are tight-fitting, or even re-shape the nervous structure they interact with, for a more selective, fascicular, access. If these are to be successfully used chronically with human nerve roots, we need to know more about the possible damage caused by the long-term entrapment and possible compression of the roots following electrode implantation. As there are, to date, no such data published, this paper presents a review of the relevant literature on alternative causes of nerve root compression, and a discussion of the degeneration mechanisms observed. A chronic compression below 40 mmHg would not compromise the functionality of the root as far as electrical stimulation and recording applications are concerned. Additionally, any temporary increase in pressure, due for example to post-operative swelling, should be limited to 20 mmHg below the patient's mean arterial pressure, with a maximum of 100 mmHg. Connective tissue growth may cause a slower, but sustained, pressure increase. Therefore, mounts large enough to accommodate the root initially without compressing it, or compliant, elastic, mounts, that may stretch to free a larger cross-sectional area in the weeks after implantation, are recommended.

Propriospinal pathways, consisting of axons from interneurons that project to other spinal segments, have been implicated as likely candidates to mediate interlimb coordination in developing and adult mammals during quadrupedal locomotion. The superficial thoracic ventrolateral funiculus (VLF) contains both ascending and descending axons, and when stimulated can induce alternating rhythmic locomotor-like activity in the lumbar ventral roots of the isolated neonatal rat spinal cord. The goal of this work was to characterize the synaptic inputs onto cervical neurons from ascending axons in the VLF. Sprague-Dawley rats (P4-P7) were deeply anesthesized with halothane and their spinal cords were isolated, removed, and maintained in vitro. Intracellular recordings were made from 68 cervical (C5-C7) neurons having 71 latency classifications in response to thoracic VLF stimulation. Antidromic (n=35), monosynaptic (n=2), di-or tri-synaptic (n=18) and long-latency polysynaptic (n=16) responses were recorded. Recordings from reduced preparations (mid-sagittal section at C5-C7) suggest that much of the delay in the long-latency polysynaptic responses require a bilaterally intact cervical spinal cord. Fifty-three percent (17/32) of the VLF responsive cervical interneurons tested also exhibited long latency excitatory responses to lumbar dorsal root stimulation suggesting that many of the cervical VLF responsive interneurons receive indirect input from lumbar primary afferents. We hypothesize that the VLF contains a population of ascending axons originating from lumbar propriospinal interneurons that can influence cervical inter- and motoneurons. These ascending VLF axons may participate in interlimb coordination by providing moment-by-moment feedback to the cervical enlargement of lumbar central pattern generator and/or hindlimb proprioceptive activity., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Most investigations into the role of the body axis in vertebrate locomotion have focused on the trunk, although in most tetrapods, the tail also plays an active role. In salamanders, the tail contributes to propulsion during swimming and to dynamic balance and maneuverability during terrestrial locomotion. The aim of the present study was to obtain information concerning the neural mechanisms that produce tail muscle contractions during locomotion in the salamander Pleurodeles waltlii. We recorded the ventral root activities in in vitro spinal cord preparations in which locomotor-like activity was induced via bath application of N-methyl-d-aspartate (20μM) and d-serine (10μM). Recordings showed that the tail spinal cord is capable of producing propagated waves of motor activity that alternate between the left and right sides. Lesion experiments further revealed that the tail rhythmogenic network is composed of a double chain of identical hemisegmental oscillators. Finally, using spinal cord preparations bathed in a chamber partitioned into two pools, we revealed efficient short-distance coupling between the trunk and tail networks. Together, our results demonstrate the existence of a pattern generator for rhythmic tail movements in the salamander and show that the global architecture of the tail network is similar to that previously proposed for the mid-trunk locomotor network in the salamander. Our findings further support the view that salamanders can control their trunk and tail independently during stepping movements. The relevance of our results in relation to the generation of tail muscle contractions in freely moving salamanders is discussed., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This depression was D(2) but not D(1) receptor dependent and was not due exclusively to depression of excitatory drive to motoneurons. Furthermore, the depression in excitation was not dependent on network activity. We next compared the modulatory effects of DA on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting, and increased amplitude. Overall, these data demonstrate that DA can potentiate network activity while at the same time reducing the gain of recurrent excitatory feedback loops from motoneurons onto the network.

A new stimulating protocol [fictive locomotion-induced stimulation (FListim)], consisting of intrinsically variable weak waveforms applied to a single dorsal root is very effective (though not optimal as it eventually wanes away) in activating the locomotor program of the isolated rat spinal cord. The present study explored whether combination of FListim with low doses of pharmacological agents that raise network excitability might further improve the functional outcome, using this in vitro model. FListim was applied together with N-methyl-d-aspartate (NMDA) + serotonin, while fictive locomotion (FL) was electrophysiologically recorded from lumbar ventral roots. Superimposing FListim on FL evoked by these neurochemicals persistently accelerated locomotor-like cycles to a set periodicity and modulated cycle amplitude depending on FListim rate. Trains of stereotyped rectangular pulses failed to replicate this phenomenon. The GABA(B) agonist baclofen dose dependently inhibited, in a reversible fashion, FL evoked by either FListim or square pulses. Sustained episodes of FL emerged when FListim was delivered, at an intensity subthreshold for FL, in conjunction with subthreshold pharmacological stimulation. Such an effect was, however, not found when high potassium solution instead of NMDA + serotonin was used. These results suggest that the combined action of subthreshold FListim (e.g., via epidural stimulation) and neurochemicals should be tested in vivo to improve locomotor rehabilitation after injury. In fact, reactivation of spinal locomotor circuits by conventional electrical stimulation of afferent fibers is difficult, while pharmacological activation of spinal networks is clinically impracticable due to concurrent unwanted effects. We speculate that associating subthreshold chemical and electrical inputs might decrease side effects when attempting to evoke human locomotor patterns.

N-methyl-d-aspartate (NMDA) receptors are of critical importance for locomotion in the developing neonatal spinal cord in rats and mice. However, due to profound changes in the expression of NMDA receptors in development between the neonatal stages and adulthood, it is unclear whether NMDA receptors are still an important component of locomotion in the adult rodent spinal cord. To shed light on this issue, we have taken advantage of recently developed preparations allowing the intracellular recording of adult motoneurons that control the tail in the sacrocaudal spinal cord of adult mice and rats. We show that in the adult sacrocaudal spinal cord, NMDA induces rhythmic activity recorded on the ventral roots, often coordinated from left to right, as in swimming motions with the tail (fictive locomotion). The adult motoneurons themselves are intrinsically sensitive to NMDA application. That is, when motoneurons are synaptically isolated with TTX, NMDA still causes spontaneous bursts of rhythmic activity, depending on the membrane potential. We show that these bursts in motoneurons depend on an NMDA-mediated persistent inward current and are terminated by the progressive activation of a persistent outward current. These results indicate that motoneurons, along with the central pattern generator, can actively participate in the production of swimminglike locomotor activity in adult rodents.

Objective: To review published series describing C1-2 posterolateral instrumentation, comparing outcomes in patients who had and did not have C2 nerve sacrifice., Methods: Online databases were searched for English-language articles between 1994 and April 2011 pertaining to posterior atlantoaxial instrumentation with C1 lateral mass and C2 screws. Twenty studies describing 732 patients with C2 nerve preservation and 6 studies describing 361 patients with C2 sacrifice met inclusion criteria., Results: All but one small study without a control group were retrospective case series, making all evidence class III. Excluding C2 nerve dysfunction, no neurological deterioration was observed. Three instances of vertebral artery injury were secondary to soft tissue dissection and one was secondary to C1 screw insertion. There were seven instances of C1 screw malposition in the preservation group and none in the section group. Reported in roughly 20% of patients, mean estimated blood loss tended to be lower with C2 nerve sectioning (213 vs. 471 mL) and operative times were somewhat shorter (118 vs. 132 minutes). C2 nerve section resulted in greater symptomatic numbness (11.6% vs. 1.3%; P < 0.0001) but less neuropathic pain (0.3% vs. 4.7%; P = 0.0002) compared with C2 preservation., Conclusions: Sacrifice of the C2 nerve root to aid in the insertion of C1 lateral mass screws when performing posterior atlantoaxial instrumented fusions is a treatment option (class III). It may decrease blood loss and operative duration, potentially advantageous in elderly or frail patients. Numbness occurred in roughly 12% of patients, an outcome that may be unacceptable to certain patient populations, but neuropathic pain was nearly absent in reported studies with nerve section. C2 nerve preservation and retraction for C1 screw placement may have higher incidence of neuropathic pain (~5%). Rates of fusion are universally high independent of C2 nerve technique., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Percutaneous spinal stimulation is a promising new technique for understanding human spinal reflexes and for evaluating the pathophysiology of motor roots. Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral junctions, sites that overlie the lumbosacral enlargement. The present study sought to determine the best location for targeting sensory and motor roots during sitting. We used paired stimuli, 50 ms apart, to distinguish the contribution of the reflex and motor components which make up the root evoked potential. This assumed that post-stimulation attenuation, primarily through homosynaptic depression, would abolish the second potential if it was trans-synaptic in origin. Conversely, successive responses would be unchanged if motor roots were being stimulated. Here, we show that sensory root reflexes were optimally elicited with percutaneous stimulation over the L1-L3 vertebrae. However, the optimal position varied between subjects and depended on the target muscle being studied. A collision test showed that the reflex recorded in pre-tibial flexors was low in amplitude and was prone to crosstalk from neighbouring muscles. In contrast to the reflex response, direct motor root activation was optimal with stimulation over the more caudal L5-S1 vertebrae. The present results support the utility of paired stimulation for evaluating the topographical recruitment of sensory and motor roots to human leg muscles.

In the rat, external urethral sphincter (EUS) activation during micturition consists of three sequential phases: 1) an increase in tonic EUS activity during passive filling and active contraction of the bladder (guarding reflex), 2) synchronized phasic activity (EUS bursting) associated with voiding, and 3) sustained tonic EUS activity that persists after bladder contraction. These phases are perturbed following spinal cord injury. The purpose of the present study was to characterize individual EUS motor unit (MU) patterns during micturition in the spinally intact and transected adult rat. EUS MU activity was recorded from either the L5 or L6 ventral root (intact) or EUS muscle (transected) during continuous flow cystometry in urethane-anesthetized adult female Sprague-Dawley rats. With the use of bladder pressure threshold and timing of activation, four distinct patterns of EUS MU activity were identified in the intact rat: low threshold sustained, medium/high threshold sustained, medium/high threshold not sustained, and burst only. In general, these MUs displayed little frequency modulation during active contraction, generated high-frequency bursts of action potentials during EUS bursting, and varied in terms of the duration of sustained tonic activity. In contrast, three general patterns of EUS MU activity were identified in the transected rat: low threshold, medium threshold, and high threshold. These MUs exhibited considerable frequency modulation during active contraction of the bladder, no bursting behavior and little to no sustained firing. The prominent frequency modulation of EUS MUs is likely due to the enhanced guarding reflex seen in EUS whole muscle electromyogram recordings in transected rats (D'Amico SC, Schuster IP, Collins WF 3rd. Exp Neurol 228: 59-68, 2011). In addition, EUS MU recruitment in transected rats more closely followed predictions by the size principle than in intact rats. This may reflect the influence of local synaptic circuits or intrinsic properties of EUS motoneurons that are active in intact rats but attenuated or absent in transected rats.

It is not well-studied how the ubiquitous neuromodulator adenosine (ADO) affects mammalian locomotor network activities. We analyzed this here with focus on roles of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)-sensitive A(1)-type ADO receptors. For this, we recorded field potentials from ventral lumbar nerve roots and electrically stimulated dorsal roots in isolated newborn rat spinal cords. At ≥ 25μM, bath-applied ADO slowed synchronous bursting upon blockade of anion-channel-mediated synaptic inhibition by bicuculline (20 μM) plus strychnine (1 μM) and this depression was countered by DPCPX (1 μM) as tested at 100 μM ADO. ADO abolished this disinhibited rhythm at ≥ 500 μM. Contrary, the single electrical pulse-evoked dorsal root reflex, which was enhanced in bicuculline/strychnine-containing solution, persisted at all ADO doses (5 μM-2 mM). In control solution, ≥ 500 μM ADO depressed this reflex and pulse train-evoked bouts of alternating fictive locomotion; this inhibition was reversed by 1 μM DPCPX. ADO (5 μM-2 mM) did not depress, but stabilize alternating fictive locomotion evoked by serotonin (10 μM) plus N-methyl-d-aspartate (4-5 μM). Addition of DPCPX (1μM) to control solution did not change either the dorsal root reflex or rhythmic activities indicating lack of endogenous A(1) receptor activity. Our findings show A(1) receptor involvement in ADO depression of the dorsal root reflex, electrically evoked fictive locomotion and spontaneous disinhibited lumbar motor bursting. Contrary, chemically evoked fictive locomotion and the enhanced dorsal root reflex in disinhibited lumbar locomotor networks are resistant to ADO. Because ADO effects in standard solution occurred at doses that are notably higher than those occurring in vivo, we hypothesize that newborn rat locomotor networks are rather insensitive to this neuromodulator., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

After peripheral nerve injury, axons often project sprouts from the node of Ranvier proximal to the damage site. It is well known that one parent axon can sprout and maintain several regenerating axons. If enough endoneurial tubes in the distal stump are present for the regenerating axons to grow along, then the number of mature myelinated nerve fibers in the distal stump will be greater than the number in the proximal stump. "Multiple regeneration" is used to describe this phenomenon in the peripheral nerve. According to previous studies, a prominent nerve containing many axons can be repaired by the multiple regenerating axons sprouting from another nerve that contains fewer axons. Most peripheral nerves contain a mixture of myelinated motor and sensory axons as well as unmyelinated sensory and autonomic axons. In this study, a multiple regeneration animal model was developed by bridging the proximal common peroneal nerve with the distal common peroneal nerve and the tibial nerve. Differences in the multiple regeneration ratio of motor and sensory nerves were evaluated using histomorphometry one month after ablating the dorsal root ganglion (DRGs) and ventral roots, respectively. The results suggest that the motor nerves have a significantly larger multiple regeneration ratio than the sensory nerves at two different time points.

In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface. The electrodes did not deteriorate after a 3 month immersion in phosphate buffered saline (PBS) at 37 °C. Due to the unique microscopic topography of the metal film on PDMS, the electrodes are extremely compliant and can withstand handling during implantation (twisting and bending) without electrical failure. The device was transplanted acutely to anaesthetized rats, and strands of the dorsal branch of roots L6 and S1 were surgically teased and inserted in three microchannels under saline immersion to allow for simultaneous in vivo recordings in an acute setting. We utilized a tripole electrode configuration to maintain background noise low and improve the signal to noise ratio. The device could distinguish two types of afferent nerve activity related to increasing bladder filling and contraction. To our knowledge, this is the first report of multichannel recordings of bladder afferent activity.

Prrxl1-CreER(T2) transgenic mice expressing tamoxifen-inducible Cre recombinase were generated by modifying a Prrxl1-containing BAC clone. Cre recombination activity was examined in Prrxl1-CreER(T2); Rosa26 reporter mice at various embryonic and postnatal stages. Pregnant mice were treated with a single dose of tamoxifen at embryonic day (E) 9.5 or E12.5, and X-gal staining was performed 2 days later. Strong X-gal staining was observed in the somatosensory ganglia (e.g., dorsal root and trigeminal ganglia) and the first central sites for processing somatosensory information (e.g., spinal dorsal horn and trigeminal nerve-associated nuclei). When tamoxifen was administered at postnatal day (P) 20 or in adulthood (P120), strong Cre recombination activity was present in the primary somatosensory ganglia, while weak Cre recombination activity was found in the spinal dorsal horn, mesencephalic trigeminal nucleus, principal sensory trigeminal nucleus, and spinal trigeminal nucleus. This mouse line provides a useful tool for exploring genes' functions in the somatosensory system in a time-controlled way., (Copyright © 2012 Wiley Periodicals, Inc.)

Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of the postnatal spinal cord that have not been investigated. In the present study, we utilized a novel transgenic mouse line to electrophysiologically characterize dI6 interneurons located close to the central canal and study their function during fictive locomotion. The majority of dI6 cells investigated were found to be rhythmically active during fictive locomotion and could be divided into two electrophysiologically distinct populations of interneurons. The first population fired rhythmic trains of action potentials that were loosely coupled to ventral root output and contained several intrinsic membrane properties of rhythm-generating neurons, raising the possibility that these cells may be involved in the generation of rhythmic activity in the locomotor CPG. The second population fired rhythmic trains of action potentials that were tightly coupled to ventral root output and lacked intrinsic oscillatory mechanisms, indicating that these neurons may be driven by a rhythm-generating network. Together these results indicate that dI6 neurons comprise an important component of the locomotor CPG that participate in multiple facets of motor behavior.

In addition to potential spinal cord injury, spinal surgery carries a risk of damage to spinal nerve roots, which could result in sensory or motor deficit. Both spontaneous and triggered electromyography (sEMG and tEMG, respectively) have been employed to reduce the risk of these deficits. This article reviews the theory and best practice of electromyographic monitoring for spinal surgery, the evidence supporting its use for various types of spine surgery, and finally, suggestions for future directions to improve knowledge and advance electromyographic monitoring of spinal nerves.

Study Design: Retrospective review study., Objectives: To identify whether it is safe to perform a magnetic resonance imaging (MRI) exam on patients who have a sacral anterior root stimulator (SARS)., Setting: Adult patients with spinal cord injury and implanted SARS attending the National Spinal Injuries Centre who have had MRI scans., Methods: Retrospective review between 1989 and 2010. The effect of the MRI scans on the function of the SARS (Finetech-Brindley, UK) was assessed up to 6 months following MRI at 0.2 and 1.5 T., Results: A total of 18 patients with SARS implants had MRI scans at 0.2 and 1.5 T of the cervical, thoracic and lumbar spine, head, shoulder and pelvis. MRI examinations were abandoned on two occasions in one patient due to radiofrequency interference. One patient's stimulator ceased to function 5 months following MRI; both of these patients showing complications had their MRI examinations at 0.2 T. There were no adverse effects at 1.5 T. In one patient the SARS was removed within 6 months after MRI due to an unrelated medical condition. A total of 17 patients showed no symptoms that required terminating the examination. In all the 11 patients with a complete and functioning implant before MRI at 1.5 T, the SARS was functioning appropriately, and no change in bladder function was reported up to 6 months following MRI., Conclusion: It is safe to perform an MRI scan on patients with SARS providing the examination is conducted in a 1.5 T system.

Different intraoperative neuromonitoring modalities (mixed-nerve somatosensory-evoked potential [M-SSEP], dermatomal somatosensory-evoked potential [D-SSEP], compound motor-evoked potential [CMEP], electromyography [EMG], and the Hoffmann reflex [H-reflex]) have been developed for early detection of nerve root injury, for timely revision, and for damage reduction. In this study, we discuss the advantages and disadvantages of M-SSEP and D-SSEP by reviewing experimental evidence from animal models and clinical practice.

Increases in lung volume inhibit the inspiratory output from the medulla, but the effect of lung inflation on the voluntary control of breathing in humans is not known. We tested corticospinal excitability using transcranial magnetic stimulation (TMS) to evoke a response in the scalene muscles. TMS was delivered at rest at three different lung volumes between functional residual capacity (FRC) and total lung capacity (TLC) during incremental inspiratory and incremental expiratory manoeuvres. Motor evoked potentials (MEPs) in scalenes were ∼50% larger at a high lung volume (FRC+∼90% inspiratory capacity [IC]) compared to lower lung volumes (FRC and FRC+∼40% IC) in both inspiratory and expiratory manoeuvres (p<0.001). The change in MEP size was not due to differences in pre-stimulus EMG amplitude (p=0.29). The results suggest a differential effect of lung inflation on the automatic and voluntary control of breathing in humans., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A new tool for locomotor circuitry activation in the non-injured human by transcutaneous electrical spinal cord stimulation (tSCS) has been described. We show that continuous tSCS over T11-T12 vertebrae at 5-40 Hz induced involuntary locomotor-like stepping movements in subjects with their legs in a gravity-independent position. The increase of frequency of tSCS from 5 to 30 Hz augmented the amplitude of evoked stepping movements. The duration of cycle period did not depend on frequency of tSCS. During tSCS the hip, knee and ankle joints were involved in the stepping performance. It has been suggested that tSCS activates the locomotor circuitry through the dorsal roots. It appears that tSCS can be used as a non-invasive method in rehabilitation of spinal pathology.

Objective: We examined the efficacy of temporary spinal cord stimulation involving the insertion of only a needle and quadripolar lead into the epidural space and applied using an extracorporeal stimulation generator for a few weeks of early postherpetic neuralgia from one to six months of its onset., Materials and Methods: Temporary spinal cord stimulation was applied in 33 patients with postherpetic neuralgia and in whom epidural block was effective. Temporary spinal cord stimulation was applied over seven days, and analgesic effects was evaluated based on visual analog scale (VAS) values before and after one, three, and six months following treatment. An analgesic effect was defined as a decrease of over 50% in the VAS value compared with before treatment., Results: VAS values decreased significantly from 68.1 mm (standard deviation [SD]± 15.2) before treatment to 37.5 mm (SD ± 20.4) after one month, to 38.0 mm (SD ± 18.7) after three months, and to 35.0 mm (SD ± 21.3) after six months. In 21/33 (63.6%) cases, an analgesic effect, defined as a decrease in the VAS value of greater than 50%, was observed one month after treatment, in 20/33 (60.6%) cases such an effect was observed three months after treatment, and in 21/33 (63.6%) cases the effect was still observed six months after treatment., Conclusions: Temporary spinal cord stimulation is an effective analgesic method for early postherpetic neuralgia from one to six months of its onset., (© 2012 International Neuromodulation Society.)

G-CSF is a glycoprotein commonly used to treat neutropenia. Recent studies have shown that the G-CSF receptor (G-CSF-R) is expressed by neurons in the central nervous system (CNS), and neuroprotective effects of G-CSF have been observed. In this study, the influence of G-CSF treatment on the glial reactivity and synaptic plasticity of spinal motoneurons in rats subjected to ventral root avulsion (VRA) was investigated. Lewis rats (7 weeks old) were subjected to unilateral VRA and divided into two groups: G-CSF and placebo treated. The drug treated animals were injected subcutaneously with 200 μg/kg/day of G-CSF for 5 days post lesion. The placebo group received saline buffer. After 2 weeks, both groups were sacrificed and their lumbar intumescences processed for transmission electron microscopy (TEM), motoneuron counting, and immunohistochemistry with antibodies against GFAP, Iba-1, and synaptophysin. Furthermore, in vitro analysis was carried out, using newborn cortical derived astrocytes. The results indicated increased neuronal survival in the G-CSF treated group coupled with synaptic preservation. TEM analyses revealed an improved preservation of the synaptic covering in treated animals. Additionally, the drug treated group showed an increase in astroglial reactivity both in vivo and in vitro. The astrocytes also presented an increased cell proliferation rate when compared with the controls after 3 days of culturing. In conclusion, the present results suggest that G-CSF has an influence on the stability of presynaptic terminals in the spinal cord as well as on the astroglial reaction, indicating a possible neuroprotective action., (Copyright © 2011 Wiley Periodicals, Inc.)