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Background: Current research lacks comprehensive investigation into the biomechanical changes in the spinal cord and nerve roots during scoliosis correction. This study employs finite element analysis to extensively explore these biomechanical variations across different Cobb angles, providing valuable insights for clinical treatment., Methods: A personalized finite element model, incorporating vertebrae, ligaments, spinal cord, and nerve roots, was constructed using engineering software. Forces and displacements were applied to achieve Cobb angle improvements, designating T1/2-T4/5 as the upper segment, T5/6-T8/9 as the middle segment, and T9/10-L1/2 as the lower segment. Simulations under traction, pushing, and traction + torsion conditions were conducted, and biomechanical changes in each spinal cord segment and nerve roots were analyzed., Results: Throughout the scoliosis correction process, the middle spinal cord segment consistently exhibited a risk of injury under various conditions and displacements. The lower spinal cord segment showed no significant injury changes under traction + torsion conditions. In the early correction phase, the upper spinal cord segment demonstrated a risk of injury under all conditions, and the lower spinal cord segment presented a risk of injury under pushing conditions. Traction conditions posed a risk of nerve injury on both sides in the middle and lower segments. Under pushing conditions, there was a risk of nerve injury on both sides in all segments. Traction + torsion conditions implicated a risk of injury to the right nerves in the upper segment, both sides in the middle segment, and the left side in the lower segment. In the later correction stage, there was a risk of injury to the upper spinal cord segment under traction + torsion conditions, the left nerves in the middle segment under traction conditions, and the right nerves in the upper segment under pushing conditions., Conclusion: When the correction rate reaches 61-68%, particular attention should be given to the upper-mid spinal cord. Pushing conditions also warrant attention to the lower spinal cord and the nerve roots on both sides of the main thoracic curve. Traction conditions require attention to nerve roots bilaterally in the middle and lower segments, while traction combined with torsion conditions necessitate focus on the right-side nerve roots in the upper segment, both sides in the middle segment, and the left-side nerve roots in the lower segment., (© 2024. The Author(s).)

Purpose: Our goal was to assess acute autonomic nervous system (ANS) response to direct sacral nerve root (SNR) stimulation in the context of lower urinary tract dysfunction., Materials and Methods: In this retrospective monocentric study, patients undergoing 2-stage sacral nerve modulation for overactive bladder, nonobstructive urinary retention, or chronic bladder pain syndrome between March 2022 and June 2023 were analyzed. A standardized stimulation protocol was applied during the lead implantation, each of the 4 contact points being sequentially stimulated at the amplitude required to elicit anal motor response. Stimulations were labeled as StimA, StimB, StimC, and StimD, ordered by ascending order of minimum amplitude required for anal motor response. Heart rate variability parameters were collected using PhysioDoloris Monitor, and computed through the time-domain (standard deviation of normal-to-normal intervals [SDNN], root mean square of successive differences), the frequency-domain (low frequency, high frequency) and the graphical (Analgesia Nociception Index [ANI]) methods., Results: Fifty patients were analyzed, including 35 females. Twelve patients had an underlying neurological disease. Efficacy was deemed achieved in 54% of patients. SDNN variability significantly increased during StimA to StimC, while maximum SDNN significantly increased only during StimA. ANI variability significantly increased during all 4 stimulations, while maximum ANI significantly increased only during StimA., Conclusions: Direct stimulation of SNR is responsible for a significant increase in ANS and relative parasympathetic nervous system activity, with a greater effect observed when the stimulation was delivered closer to the SNR. These results shed light on potential mechanisms underlying sacral nerve modulation, particularly regarding the treatment of ANS dysregulation in lower urinary tract dysfunction.

Background: Central nervous system (CNS) disorders, such as stroke, often lead to spasticity, which result in limb deformities and significant reduction in quality of life. Spasticity arises from disruptions in the normal functioning of cortical and descending inhibitory pathways in the brainstem, leading to abnormal muscle contractions. Contralateral seventh cervical nerve cross transfer (CC7) surgery has been proven to effectively reduce spasticity, but the specific mechanism for its effectiveness is unclear., Methods: This study aimed to investigate the changes in the dorsal root ganglia (DRG) following CC7 surgery. A comprehensive anatomical analysis was conducted through cadaveric study and magnetic resonance imaging (MRI) study, to accurately measure the regional anatomy of the C7 DRG. DRG perfusion changes were quantitatively assessed by comparing pre- and postoperative dynamic contrast-enhanced (DCE) MRI., Results: In CC7 surgery, the C7 nerve root on the affected side is cut close to the DRG (3.6 ± 1.0 mm), while the C7 nerve root on the healthy side is cut further away from the DRG (65.0 ± 10.0 mm). MRI studies revealed that after C7 proximal neurotomy on the affected side, there was an increase in DRG volume, vascular permeability, and perfusion; after C7 distal neurotomy on the healthy side, there was a decrease in DRG volume, with no significant changes in vascular permeability and perfusion., Conclusion: This study provides preliminary insights into the mechanisms of spasticity reduction following CC7 surgery, indicating that changes in the DRG, such as increased vascular permeability and perfusion, could disrupt abnormal spinal γ-circuits. The resulting high-perfusion state of DRG, possibly due to heightened neuronal activity and metabolic demands, necessitating further research to verify this hypothesis., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

On demand and localized treatment for excessive muscle tone after spinal cord injury (SCI) is currently not available. Here, we examine the reduction in leg hypertonus in a person with mid-thoracic, motor complete SCI using a commercial transcutaneous electrical stimulator (TES) applied at 50 or 150 Hz to the lower back and the possible mechanisms producing this bilateral reduction in leg tone. Hypertonus of knee extensors without and during TES, with both cathode (T11-L2) and anode (L3-L5) placed over the spinal column (midline, MID) or 10 cm to the left of midline (lateral, LAT) to only active underlying skin and muscle afferents, was simultaneously measured in both legs with the pendulum test. Spinal reflexes mediated by proprioceptive (H-reflex) and cutaneomuscular reflex (CMR) afferents were examined in the right leg opposite to the applied LAT TES. Hypertonus disappeared in both legs but only during thoracolumbar TES, and even during LAT TES. The marked reduction in tone was reflected in the greater distance both lower legs first dropped to after being released from a fully extended position, increasing by 172.8% and 94.2% during MID and LAT TES, respectively, compared with without TES. Both MID and LAT (left) TES increased H-reflexes but decreased the first burst, and lengthened the onset of subsequent bursts, in the cutaneomuscular reflex of the right leg. Thoracolumbar TES is a promising method to decrease leg hypertonus in chronic, motor complete SCI without activating spinal cord structures and may work by facilitating proprioceptive inputs that activate excitatory interneurons with bilateral projections that in turn recruit recurrent inhibitory neurons. NEW & NOTEWORTHY We present proof of concept that surface stimulation of the lower back can reduce severe leg hypertonus in a participant with motor complete, thoracic spinal cord injury (SCI) but only during the applied stimulation. We propose that activation of skin and muscle afferents from thoracolumbar transcutaneous electrical stimulation (TES) may recruit excitatory spinal interneurons with bilateral projections that in turn recruit recurrent inhibitory networks to provide on demand suppression of ongoing involuntary motoneuron activity.

Objective: Sacral anterior root stimulation (SARS) was developed 40 years ago to restore urinary and bowel functions to individuals with spinal cord injury. Mostly used to restore lower urinary tract function, SARS implantation is coupled with sacral deafferentation to counteract the problems of chronic detrusor sphincter dyssynergia and detrusor overactivity. In this article, we systematically review 40 years of SARS implantation and assess the medical added value of this approach in accordance with the PRISMA guidelines. We identified 4 axes of investigation: 1) impact on visceral functions, 2) implantation safety and device reliability, 3) individuals' quality of life, and 4) additional information about the procedure., Methods: A systematic review was performed. Three databases were consulted: PubMed, EBSCOhost, and Pascal. A total of 219 abstracts were screened and 38 articles were retained for analysis (1147 implantations)., Results: The SARS technique showed good clinical results (85.9% of individuals used their implant for micturition and 67.9% to ease bowel movements) and improved individual quality of life. Conversely, several sources of complications were reported after implantation (e.g., surgical complications and failure)., Conclusions: Despite promising results, a decline in implantations was observed. This decline can be linked to the complication rate, as well as to the development of new therapeutics (e.g., botulinum toxin) and directions for research (spinal cord stimulation) that may have an impact on people. Nevertheless, the lack of alternatives in the short-term suggests that the SARS implant is still relevant for the restoration of visceral functions after spinal cord injury., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Brachial plexus root avulsions cause debilitating upper limb paralysis. Short-term neuroprotective treatments have reported preservation of motor neurons and function in model animals while reports of long-term benefits of such treatments are scarce, especially the morphological sequelae. This morphological study investigated the long-term suppression of c-Jun- and neuronal nitric oxide synthase (nNOS) (neuroprotective treatments for one month) on the motor neuron survival, ultrastructural features of lower motor neurons, and forelimb function at six months after brachial plexus roots avulsion. Neuroprotective treatments reduced oxidative stress and preserved ventral horn motor neurons at the end of the 28-day treatment period relative to vehicle treated ones. Motor neuron sparing was associated with suppression of c-Jun, nNOS, and pro-apoptotic proteins Bim and caspases at this time point. Following 6 months of survival, neutral red staining revealed a significant loss of most of the motor neurons and ventral horn atrophy in the avulsed C6, 7, and 8 cervical segments among the vehicle-treated rats ( n = 4). However, rats that received neuroprotective treatments c-Jun JNK inhibitor, SP600125 ( n = 4) and a selective inhibitor of nNOS, 7-nitroindazole ( n = 4), retained over half of their motor neurons in the ipsilateral avulsed side compared. Myelinated axons in the avulsed ventral horns of vehicle-treated rats were smaller but numerous compared to the intact contralateral ventral horns or neuroprotective-treated groups. In the neuroprotective treatment groups, there was the preservation of myelin thickness around large-caliber axons. Ultrastructural evaluation also confirmed the preservation of organelles including mitochondria and synapses in the two groups that received neuroprotective treatments compared with vehicle controls. Also, forelimb functional evaluation demonstrated that neuroprotective treatments improved functional abilities in the rats. In conclusion, neuroprotective treatments aimed at suppressing degenerative c-Jun and nNOS attenuated apoptosis, provided long-term preservation of motor neurons, their organelles, ventral horn size, and forelimb function.

We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Before euthanasia, pelvic or transferred nerves and L1-S3 spinal roots were stimulated and maximum detrusor pressure (MDP) recorded. Bladder specimens were collected for histological and ex vivo smooth muscle contractility studies. Both reinnervated and decentralized animals showed less or denuded urothelium, fewer intramural ganglia, and more inflammation and collagen, than controls, although percent muscle was maintained. In reinnervated animals, pgp9.5+ axon density was higher compared with decentralized animals. Ex vivo smooth muscle contractions in response to KCl correlated positively with submucosal inflammation, detrusor muscle thickness, and pgp9.5+ axon density. In vivo, reinnervated animals showed higher MDP after stimulation of L1-L6 roots compared with their transected L7-S3 roots, and reinnervated and decentralized animals showed lower MDP than controls after stimulation of nerves (due likely to fibrotic nerve encapsulation). MDP correlated negatively with detrusor collagen and inflammation, and positively with pgp9.5+ axon density and intramural ganglia numbers. These results demonstrate that bladder function can be improved by transfer of obturator nerves to pelvic nerves at 1 yr after decentralization, although the fibrosis and inflammation that developed were associated with decreased contractile function.

Introduction: Chronic immune polyradiculopathies (sensory, motor, and mixed) are uncommon., Methods: In this single-center, retrospective study, the inclusion criteria for participants were progressive sensory ataxia and/or areflexic limb weakness; tibial somatosensory evoked potential (SSEP) abnormalities of the N22 and P40 potentials with normal sensory and motor nerve conduction studies or root involvement, according to magnetic resonance imaging (MRI); and albuminocytological dissociation., Results: Eight patients were included in our study. Two had weakness, two had sensory ataxia, and four had both weakness and ataxia. Patients with weakness had abnormal SSEPs and patients with sensory ataxia also had absent F waves. Electromyography showed chronic denervation. MRI scans confirmed thickening and enhancement of roots. The patients responded to corticosteroid treatment., Discussion: The overlapping clinicoelectrophysiological findings and similarities in radiological and therapeutic responses suggest that these entities are clinical variants of the same disease. The terms CIS(m)P, CI(s)MP, and CISMP (for chronic immune sensory motor polyradiculopathy) could be used to denote the predominant clinical involvement., (© 2020 Wiley Periodicals LLC.)

Introduction: The eight cervical nerve might be a source of input to the auditory system., Objectives: The object was to assess the efficacy of infiltration of the eight cervical nerve root for treating tinnitus patients and to find indicators for a successful result., Design: Retrospective cohort study. Subjects were 79 tinnitus patients visiting our clinic in a three-year period and who were treated with infiltration of the eight cervical nerve root., Results: Twenty-six percent of the tinnitus patients had a reduction of their tinnitus following an infiltration of the eight cervical nerve root. Most of the successfully treated patients rated the effect of therapy as a moderate reduction of 25% to 50%. Fifty percent of the successful treated patients still had benefit at 6.6 months. In 5% of the patients, their tinnitus was aggravated after the infiltration of the eight cervical nerve roots. Patients with a hearing loss at 500 Hz that exceed the hearing loss at 2 kHZ responded the most to infiltration of the eight cervical nerve., Conclusion: Infiltration of the eight cervical nerve root reduced the intensity of tinnitus in 26% of the cohort of 79 tinnitus patients with a moderate to good effect. This therapy for tinnitus patients' needs to be considered, especially in those with a hearing loss at 500 Hz that exceed the hearing loss at 2 kHZ.

Introduction: Treating cervical spine disorders can result in a reduction of tinnitus., Objectives: The object of the study was to ascertain the benefit of therapy of the third and fourth cervical nerves in reducing tinnitus and to assess parameters indicating a long-term relief., Design: Subjects were 37 tinnitus patients who were treated with infiltration of the third and fourth cervical nerves. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview., Results: In a group of tinnitus patients, 19% of the patients reported less tinnitus after therapy of the third and fourth cervical nerves. Most of the patients had a moderate reduction of 25% to 50%. At 3.8 months, 50% of the successful treated patients still had a positive effect. No adverse events of the procedure were observed. The combination of an evident anterior spur at the third cervical vertebrae together with less hearing at 2 kHz indicate patients who responded the best to therapy of the third and fourth cervical nerves., Conclusions: Treating cervical spine disorders can reduce tinnitus. In a group of tinnitus patients, 19% of the patients had less tinnitus after therapy of the C3 and C4. Screening of tinnitus patients is needed for the proper selection of the ones who could benefit from a somatic approach. In our study, the combination of an evident anterior spur at the third cervical vertebrae together with less hearing at 2 kHz indicate patients who responded the best following therapy of the C3 and C4.

We aimed to compare the electrophysiology and magnetic resonance neurography (MRN) results of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) subtypes and to explore the progression from atypical CIDP to typical CIDP. We collected the medical records of 45 CIDP patients to analyse the rate of progression from atypical CIDP to typical CIDP subtypes. The cerebrospinal fluid (CSF) protein (p = 0.024) and overall disability sum score (ODSS) (p = 0.000) differed among patients with typical CIDP, distal acquired demyelinating symmetric neuropathy (DADS) and Lewis-Sumner syndrome (LSS). The compound motor action potential (CMAP) of typical CIDP was lower than that of the other subtypes (p = 0.016, p = 0.022 and p = 0.012). The cross-sectional area (CSA) of nerve roots in typical CIDP was significantly thicker than that of nerve roots in DADS and LSS. There were fewer DADS and LSS patients who progressed to typical CIDP than those who progressed to pure motor and pure sensory CIDP (p = 0.000), and the progression from pure motor to typical CIDP required a significantly longer time than the progression from pure sensory to typical CIDP (p = 0.007). Typical CIDP was more severe than the other subtypes not only in terms of clinical and electrophysiology factors but also in terms of MRN factors.

Purpose of Review: To provide an overview of available electrical stimulation devices in neurogenic patients with lower urinary tract disease., Recent Findings: It is advocated to do more studies in neurogenic patients as results seem promising and useful but most studies did not include neurogenic patients or neurogenic patients were not analyzed or reported separately. Most studies included a small heterogenous neurogenic group with multiple pathophysiologic origin focusing on effect of a treatment instead of results of a treatment in a specific neurogenic group. Neuromodulation or stimulation has the advantage that it acts on different organs, like bladder and bowel, so can treat neurogenic patients, who mostly suffer from multiple organ failure., Summary: Brindley procedure, sacral neuromodulation (SNM) and posterior tibial nerve stimulation (PTNS) are available for a while already. The Brindley procedure (including sacral anterior root stimulation in combination with a rhizotomy of posterior sacral roots) is developed for selected spinal cord injury patient with a complete spinal injury, and has shown results for many years in neurogenic patients. An alternative to the rhizotomy is not established yet. SNM and PTNS are other modalities that are used in nonneurogenic patients, but are not yet indicated and much studied in neurogenic patients.

Objectives: Adenosine has an analgesic and anti-inflammatory role and its injections are used for perioperative pain management. We aimed to study efficacy of intrathecal injection of adenosine for post-operative radicular pain after lumbar discectomy. Forty patients with unilevel lumbar discectomy who had radicular lower limb pain were treated by 1000 micrograms of intrathecal injection of adenosine in this single-arm prospective open-label trial between November 2015 to October 2016. Radicular pain severity using visual analogue scale (VAS) and pain killer consumption per day were assessed during a 3 months follow up period., Results: Radicular pain severity was significantly reduced in 3 month follow-up period in comparison to the baseline (F = 19,760, df = 2.53, p-value < 0.001). Further, painkiller medication consumption rate in average during 3 month follow-up period after injection was significantly lower in comparison to baseline (F = 19.244, df = 1.98, p-value < 0.001). This study suggests that intrathecal injection of 1000 micrograms adenosine is a safe and effective method for post-operative neuropathic pain management after uni-level disk surgeries. Trial registration IRCT201608171772N20, Retrospectively registered on 2016-08-28.

Introduction: We investigated the feasibility of motor unit number index (MUNIX) in quantitatively assessing motor root lesions and tracking different treatment outcomes in lumbosacral radiculopathy (LR)., Methods: Bilateral MUNIX was recorded from the abductor hallucis, extensor digitorum brevis, and tibialis anterior in 44 normal controls and 108 patients with LR, and this was repeated approximately 12 months after treatment in 60 patients with LR., Results: More abnormalities were observed when side-to-side differences of MUNIX measurements were used to evaluate LR (P < .05). Motor unit number index measurements worsened without progression of muscle weakness after conservative treatment, and MUNIX measurements improved with or without increased muscle strength after surgical treatment (P < .05)., Discussion: Motor unit number index may identify a specific L5 or S1 motor root lesion even before muscle weakness occurs, especially when side-to-side differences are used. Changes in MUNIX were larger than those in motor function measures after treatments for LR., (© 2020 Wiley Periodicals, Inc.)

The loss of descending serotonin (5-HT) to the spinal cord contributes to muscle spasms in chronic spinal cord injury (SCI). Hyperexcitable motoneurons receive long-lasting excitatory postsynaptic potentials (EPSPs), which activate their persistent inward currents to drive muscle spasms. Deep dorsal horn (DDH) neurons with bursting behavior could be involved in triggering the EPSPs due to loss of inhibition in the chronically 5-HT-deprived spinal cord. Previously, in an acutely transected preparation, we found that bursting DDH neurons were affected by administration of the 5-HT 1B/1D receptor agonist zolmitriptan, which suppressed their bursts, and by N -methyl-d-aspartate (NMDA), which enhanced their bursting behavior. Nonbursting DDH neurons were not influenced by these agents. In the present study, we investigate the firing characteristics of bursting DDH neurons following chronic spinal transection at T10 level in adult mice and examine the effects of replacing lost endogenous 5-HT with zolmitriptan. Terminal experiments using our in vitro preparation of the sacral cord were carried out ~10 wk postransection. Compared with the acute spinal stage of our previous study, DDH neurons in the chronic stage became more responsive to dorsal root stimulation, with burst duration doubling with chronic injury. The suppressive effects of zolmitriptan were stronger overall, but the facilitative effects of NMDA were weaker. In addition, the onset of DDH neuron activity preceded ventral root output and the firing rates of DDH interneurons correlated with the integrated long-lasting ventral root output. These results support a contribution of the bursting DDH neurons to muscle spasms following SCI and inhibition by 5-HT. NEW & NOTEWORTHY We investigate the firing characteristics of bursting deep dorsal horn (DDH) neurons following chronic spinal transection. DDH neurons in the chronic stage are different from those in the acute stage as noted by their increase in excitability overall and their differing responses serotonin (5-HT) and N -methyl-d-aspartate (NMDA) receptor agonists. Also, there is a strong relationship between DDH neuron activity and ventral root output. These results support a contribution of the bursting DDH neurons to muscle spasms following chronic spinal cord injury (SCI).

Background: Radiculopathies caused by spinal stenosis in the upper lumbar spinal canal (L1/2, L2/3, L3/4) have not been comprehensively investigated., Methods: This retrospective study reviewed 14 patients from a tertiary hospital outpatient clinic. The inclusion criteria were upper lumbar stenosis seen on MRI and radiculopathies with active denervation confirmed on electromyography. Patients with any other conditions that could explain the clinical or electrophysiological manifestations were excluded., Results: Neurogenic findings were predominantly observed in L5 or S1 myotomes on electromyography. Abnormal spontaneous activity was observed in distal muscles in all patients and in proximal muscles in eight patients. Axonal involvement was bilateral in 10 patients and unilaterally in 4 patients. MRI showed redundant nerve roots in 13 patients with chronic reinnervation on electromyography., Conclusions: Upper lumbar spinal stenosis usually causes L5 or S1 radiculopathies with diverse patterns. This discrepancy may cause diagnostic confusion., (© 2020 Wiley Periodicals, Inc.)

Object: Spinal cord surgeries carry a high risk for significant neurological impairments. The initial techniques for spinal cord mapping emerged as an aid to identify the dorsal columns and helped select a safe myelotomy site in intramedullary tumor resection. Advancements in motor mapping of the cord have also been made recently, but exclusively with tumor surgery. We hereby present our experiences with dynamic mapping of the corticospinal tract (CST) in other types of spinal cord procedures that carry an increased risk of postoperative motor deficit, and thus could directly benefit from this technique., Case Reports: Two patients with intractable unilateral lower extremity pain due to metastatic disease of the sacrum and a thoraco-lumbar chordoma, respectively underwent thoracic cordotomy to interrupt the nociceptive pathways. A third patient with progressive leg weakness underwent cord untethering and surgical repair of a large thoracic myelomeningocele. In all three cases, multimodality intraoperative neurophysiologic testing included somatosensory and motor evoked potentials monitoring as well as dynamic mapping of the CST., Conclusion: CST mapping allowed safe advancement of the cordotomy probe and exploration of the meningocele sac with untethering of the anterior-lateral aspect of the cord respectively, resulting in postoperative preservation or improvement of motor strength from the pre-operative baseline. Stimulus thresholds varied likely with the distance between the stimulating probe and the CST as well as with the baseline motor strength in the mapped myotomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: We aim to non-invasively facilitate activation of spared neural circuits after cervical spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). We developed and tested a novel configuration for cervical transcutaneous spinal stimulation (cTSS)., Methods: cTSS was delivered via electrodes placed over the midline at ~T2-T4 levels posteriorly and ~C4-C5 levels anteriorly. Electromyographic responses were measured in arm and hand muscles across a range of stimulus intensities. Double-pulse experiments were performed to assess homosynaptic post-activation depression (PAD). Safety was closely monitored., Results: More than 170 cTSS sessions were conducted without major safety or tolerability issues. A cathode-posterior, 2 ms biphasic waveform provided optimal stimulation characteristics. Bilateral upper extremity muscle responses were easily obtained in subjects with SCI and ALS. Resting motor threshold at the abductor pollicis brevis muscle ranged from 5.5 to 51.0 mA. As stimulus intensity increased, response latencies to all muscles decreased. PAD was incomplete at lower stimulus intensities, and decreased at higher stimulus intensities., Conclusions: Posteroanterior cTSS has the capability to target motor neurons both trans-synaptically via large-diameter afferents and non-synaptically via efferent motor axons., Significance: Posteroanterior cTSS is well tolerated and easily activates upper extremity muscles in individuals with SCI and ALS., (Published by Elsevier B.V.)

Spinal root avulsion typically leads to massive motoneuron death and severe functional deficits of the target muscles. Multiple pathological factors such as severe neuron loss, induction of inhibitory molecules, and insufficient regeneration are responsible for the poor functional recovery. Leucine-rich repeat and immunoglobulin-like domain-containing Nogo receptor-interacting protein 1 (LINGO-1), a central nervous system (CNS)-specific transmembrane protein that is selectively expressed on neurons and oligodendrocytes, serves as a potent negative mediator of axonal regeneration and myelination in CNS injuries and diseases. Although accumulating evidence has demonstrated improvement in axonal regeneration and neurological functions by LINGO-1 antagonism in CNS damage, the possible effects of LINGO-1 in spinal root avulsion remain undiscovered. In this study, a LINGO-1 knockdown strategy using lentiviral vectors encoding LINGO-1 short hairpin interfering RNA (shRNA) delivered by the Pluronic F-127 (PF-127) hydrogel was described after brachial plexus avulsion (BPA). We provide evidence that following BPA and immediate reimplantation, transplantation of LINGO-1 shRNA lentiviral vectors encapsulated by PF-127 rescued the injured motoneurons, enhanced axonal outgrowth and myelination, rebuilt motor endplates, facilitated the reinnervation of terminal muscles, improved angiogenesis, and promoted recovery of avulsed forelimbs. Altogether, these data suggest that delivery of LINGO-1 shRNA by a gel scaffold is a potential therapeutic approach for root avulsion. Impact Statement In this study, we attempted transplantation of lentivirus (LV)/leucine-rich repeat and immunoglobulin-like domain-containing Nogo receptor-interacting protein 1 (LINGO-1)-short hairpin interfering RNA (shRNA) encapsulated by the Pluronic F-127 (PF-127) hydrogel into a brachial plexus avulsion (BPA)-reimplantation model. We found that administration of LV/LINGO-1 shRNA facilitates neuron survival and axonal regeneration, attenuates muscle atrophy and motor endplate (MEP) loss, enhances neovascularization, and promotes functional recovery in BPA rats. Co-transplantation of LV/LINGO-1 shRNA and gel reinforces the survival-promoting effect, axonal outgrowth, and angiogenesis in comparison with LV/LINGO-1 shRNA application alone. Our research provides evidence that LV /LINGO-1 shRNA delivered by PF-127 represents a new treatment strategy for BPA repair.

Objective: This retrospective cohort study aimed to investigate the change of spinal cord displacements and the occurrence of C5 palsy between anterior controllable antedisplacement and fusion (ACAF) (group A) and single open-door laminoplasty (group L)., Methods: From January 2016 to December 2017, a total of 80 patients with cervical ossification of the posterior longitudinal ligament (OPLL) were enrolled. All patients underwent computed tomography and magnetic resonance imaging. The types and extent of OPLL, spinal cord rotation, deviation angle, and distance between the vertebral arteries line and spinal cord (DVS) were measured. Patients with postoperative C5 palsy were recorded. Neurologic function was evaluated by Japanese Orthopaedic Association (JOA) score., Results: Three days after surgery, patients in group A had better recovery (6.7° ± 2.4°) of spinal cord rotation than group L (3.1° ± 0.8°; P < 0.05). Deviation angle showed similar changes to spinal cord rotation. At the final follow-up, patients in group A had decreased DVS (11.0 ± 0.7 mm), whereas patients in group L had increased DVS (15.1 ± 0.8 mm) compared with preoperation (P < 0.05). Five patients (1 in group A and 4 in group L) developed postoperative C5 palsy (P > 0.05). Patients in group A had a higher JOA score at the final follow-up than those in group L (P < 0.05)., Conclusions: ACAF could achieve in situ decompression in terms of spinal cord rotation, deviation angle, and spinal cord shift with better clinical outcomes and relatively lower incidence of C5 palsy compared with single open-door laminoplasty., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate the application of multimodal intraoperative monitoring (MIOM) system in patients with congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS).Twelve patients who underwent posterior surgical correction of scoliosis for CS and AIS from June 2014 to July 2018 were enrolled in this study. During the operation, we monitored the functional status of the spinal cord by MIOM. An abnormal somatosensory evoked potential was defined as a prolonged latency of more than 10% or a peak-to-peak amplitude decline of more than 50% when compared to baseline. An abnormal transcranial motor evoked potential (TcMEP) was defined as a TcMEP amplitude decrease of more than 50%. A normal triggered electromyography response, which presented with the absence of an electrical response on stimulation at 8.2 mA, indicated that the pedicle screw was not in contact with the spinal cord or nerve root.A total of 12 patients underwent MIOM surgery, of which 9 patients with negative MIOM had no significant deterioration of neurological function postoperatively, and exhibited satisfactory surgical correction of scoliosis during follow-ups. However, the remaining 3 patients suffered from MIOM events, 2 patients had normal neurological function, and 1 patient had deteriorated neurological function postoperatively.Using MIOM in CS and AIS surgery could promptly detect iatrogenic neurological injury at the early stage. Therefore, rapid response by appropriate intraoperative interventions can be taken to minimize the injury. Besides, stable MIOM recordings encourage surgeons to correct scoliosis even when the Cobb angle of scoliosis was extremely large.

Bowstring disease (BSD) is a new classification of spine disease caused by axial stretched lesion on nerve roots and the spinal cord, which is differentiated from disc herniation and canal stenosis in that it is caused by nerve compression lesions. BSD could be caused by mismatched growth rates between the spine and nerve roots (the juvenile type), or by imbalanced degenerative rates between the spine column and nerve roots (degenerative type). Here, we propose that there are several self-adjust mechanisms to relieve axial nerve tension: (i) nerve growth; (ii) posture adjustment and low back pain; (iii) autogenous degeneration of intervertebral disc; and (iv) idiopathic and degenerative scoliosis. Iatrogenic lesions could also result in BSD, which could be presented as adjacent segment degeneration, leading to adding-on effects and other neurological symptoms. The diagnosis criteria are proposed based on symptoms, physical examination, and radiological presentations. To remove axial tension on nerve roots, lumbar surgery should aim to restore the coordination of spine and cord units. Capsule surgery, shortening the spine column, could decompress cord and nerve roots 3-dimensionally., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Up to 40% of patients diagnosed with lumbar spinal stenosis (LSS) show evidence of redundant nerve roots (RNR) of the cauda equina on their magnetic resonance images (MRI). The etiology of RNR is still unclear. Preoperative evidence of RNR is associated with a worse postsurgical outcome. Consequently, potential predictors of RNR could have a prognostic value. The aim was to test whether patient demographics and MRI-based measurements can predict RNR in LSS patients., Methods: In a retrospective database-based cohort study the preoperative data of 300 patients, 150 with (RNR+) and 150 without (RNR-) evidence of RNR on their MRI were analyzed. Three independent researchers performed the MRI reads. Potential predictors were age, gender, body height (BH), length of lumbar spine (LLS), segmental length of lumbar spine (SLLS), lumbar spine alignment deviation (LSAD), relative LLS (rLLS), relative SLLS (rSLLS), number of stenotic levels (LSS-level), and grade of LSS severity (LLS-grade, increasing from A to D). Binomial logistic regression models were performed., Results: RNR+ patients were 2.6 years older (p = 0.01). Weak RNR+ predictors were a two-years age increase (OR 1.06; p = 0.02), 3 cm BH decrease (OR 1.09; p = 0.01) and a 5 mm SLLS decrease (OR 1.34; p < 0.001). Strong RNR+ predictors were a 1% rLLS decrease (OR 2.17; p < 0.001), LSS-level ≥ 2 (OR 2.59; p = 0.001), LLS-grade C (OR 5.86; p = 0.02) and LLS-grade D (OR 18.4; p < 0.001). The mean rSLLS of RNR+ patients was 0.6% shorter (p < 0.001; 95% C.I. 0.4 to 0.8) indicating a disproportionate shorter lumbar spine., Conclusions: We identified LSS severity grade and LSS levels as the strongest predictors of RNR. In addition to previous studies, we conclude that a shortened lumbar spine by degeneration is involved in the development of RNR.

This paper illustrates the cases of two patients with an acute onset of right brachial neuropathic pain, flaccid paralysis and contralateral thermal and thermal pain hypoesthesia, without posterior column impairment nor pyramidal signs below the segmental lesion. MRI showed right sided spinal cord infarction, in the anterior spinal artery territory between C1 and C5 in one patient and between C3 and C7 in the other. Contact Heat Evoked Potentials and Quantitative Thermal Sensory testing are consistent with contralateral, but not ipsilateral, spinothalamic tract involvement. Electromyographic results established ipsilateral segmental denervation and somatosensory evoked responses were consistent with dorsal column sparing. Unilateral anterior cervical spinal cord infarction may present with acute ipsilateral segmental neuropathic pain, lower motor neurone-type weakness, contralateral thermoanalgesia and no pyramidal signs. The ipsilateral pain provides novel evidence that in some instances, ventral roots can play a role in nociception in humans. The infarcted territory may result from occlusion of a sulcal commissural artery or a number of more proximal vessels (including a single or duplicated anterior spinal artery, vertebral arteries or feeding radicular arteries)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The external anal sphincter (EAS) is important for the maintenance of bowel continence and may be compromised by a variety of neuropathic conditions. However, large animal models for the study of EAS functions have been sparse. The EAS guarding reflex was examined by electromyography (EMG) in neurologically intact rhesus macaques ( n = 6) and at 4-6 wk after a unilateral EAS denervation from an L6-S3 ventral root avulsion (VRA) injury ( n = 6). Baseline EAS EMG recordings were quiescent in all subjects, and evoked responses showed an initial large-amplitude EMG activity, which gradually returned to baseline within 1-2 min. At 4-6 wk postoperatively, the EAS guarding reflex showed a significantly reduced EMG response duration of 47 ± 15 s and area under the curve (AUC) of 0.198 ± 0.097 mV·s compared with the corresponding evoked EAS EMG duration of 102 ± 19 s and AUC of 0.803 ± 0.225 mV·s ( P < 0.05) in the control group. Detailed time- and frequency-domain analysis of the evoked EAS EMG responses for the first 40 s showed no difference between groups for the maximum amplitude but a significant decrease for the mean amplitude across the study period and an early AUC reduction for the first 10 s in the VRA injury group. Time-frequency analysis and power spectrum plots indicated decreased intensity and a narrower midrange of frequencies in the VRA injury group. We conclude that the EAS guarding reflex in rhesus macaques shows characteristic EMG features in control subjects and signs of partial target denervation after a unilateral L6-S3 VRA injury. NEW & NOTEWORTHY The external anal sphincter guarding reflex showed initial large-amplitude peaks and a gradual return to a quiescent baseline after a rectal probe stimulus in rhesus macaques. At 4-6 wk after a unilateral ventral root avulsion (VRA) injury, the electromyography duration, mean amplitude, and area under the curve measurements were decreased. Time-frequency analysis and power spectrum plots indicated decreased intensity and a narrowed midrange of frequencies in the VRA injury cohort.

Purpose: The pain involved in the herniated discs could be generated by some mobility of the nerve roots during straight leg raising (SLR). SLR produces some movement of nerves, but the magnitude of this displacement needs to be thorough, that is why we have investigated lumbo-sacral nerve root displacement in the spinal canal during the passive straight leg raise (SLR)., Methods: Fourteen cadavers underwent laminectomy to mark the nerve roots of L2-S1 with lead balls. X-rays were taken during different movements imposed on the body: bilateral hip extension, left SLR then right and bilateral SLR. By superimposing these images two by two, the displacement of the nerve roots is quantified numerically during the various SLR maneuvers with respect to the reference position corresponding to the bilateral hip extension., Results: The median range of the different nerve root movements ranged from 0.10 to 0.51 cm (p < 0.05 except for the L2 root) when the left SLR is applied, from 0.26 to 0.48 cm (p < 0.05) with the right SLR and from 0.30 to 0.65 cm (p < 0.05) with a bilateral SLR. No statistically significant relationship was found between age and movement value., Conclusions: The lumbo-sacral nerve roots in the spinal canal region move statistically significantly in response to the clinically applied SLR test, except for L2 root during the left SLR. This movement is symmetric and greater when a bilateral SLR is applied. These anatomical results are correlated with those observed empirically in clinical practice.

Aims: To assess bladder smooth muscle function and innervation after long-term lower spinal root transection in canines., Methods: Thirteen female mixed-breed hound dogs underwent bladder decentralization, which included transection of all sacral dorsal and ventral roots caudal to L7 and hypogastric nerves, bilaterally (n = 3); all sacral roots and hypogastric nerves plus transection of L7 dorsal roots, bilaterally (n = 4); or a sham operation (n = 6). At a year after initial surgery, bladder function was assessed in vivo by stimulation of the pelvic plexus. The bladder tissue was harvested for ex vivo smooth muscle contractility studies. Remaining bladder was evaluated for nerve morphology immunohistochemically using neuronal marker PGP9.5, apoptotic activity using terminal deoxynucleotidyl transferase dUTP nick end labeling, and histopathology using a hematoxylin and eosin stain., Results: Sacral root decentralization did not reduce maximum strength of pelvic plexus stimulation-induced bladder contraction, although long-term sacral dorsal and ventral root plus L7 dorsal root transection significantly decreased contraction strength. Electric field stimulation-induced contractions of the detrusor from all decentralized animals were preserved, compared to controls. Viable nerves and intramural ganglia were visualized in the bladder wall, regardless of group. There was no difference in amount of apoptosis in bladder smooth muscle between groups., Conclusion: Bladder smooth muscle cells maintain their function after long-term bladder decentralization. While pelvic plexus-induced bladder contractions were less robust at 1 year after lower spinal root transection, the absence of atrophy and preservation of at least some nerve activity may allow for successful surgical reinnervation after long-term injury., (© 2018 Wiley Periodicals, Inc.)

Objective: To improve understanding of disease pathophysiology in anti-myelin-associated glycoprotein (anti-MAG) neuropathy to guide further treatment approaches., Methods: Anti-MAG neuropathy patients underwent clinical assessments, nerve conduction and excitability studies, and ultrasound assessment., Results: Patients demonstrated a distinctive axonal excitability profile characterised by a reduction in superexcitability [MAG: -14.2 ± 1.6% vs healthy controls (HC): -21.8 ± 1.2%; p < 0.01] without alterations in most other excitability parameters. Mathematical modelling of nerve excitability recordings suggested that changes in axonal function could be explained by a 72.5% increase in juxtaparanodal fast potassium channel activation and an accompanying hyperpolarization of resting membrane potential (by 0.3 mV) resulting in a 94.2% reduction in discrepancy between anti-MAG data and the healthy control model. Superexcitability changes correlated strongly with clinical and neurophysiological parameters. Furthermore, structural assessments demonstrated a proximal pattern of nerve enlargement (C6 nerve root cross-sectional area: 15.9 ± 8.1 mm 2 vs HC: 9.1 ± 2.3 mm 2 ; p < 0.05)., Conclusions: The imaging and neurophysiological results support the pathogenicity of anti-MAG IgM. Widening between adjacent loops of paranodal myelin due to antibodies would expand the pathway from the node to the juxtaparanode, increasing activation of juxtaparanodal fast potassium channels, thereby impairing saltatory conduction., Significance: Potassium channel blockers may prove beneficial in restoring conduction closer to its normal state and improving nerve function in anti-MAG neuropathy., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Our objective is to use the area of the motor evoked potential (MEP) as a diagnostic tool for intraoperative radicular injury., Methods: We analyzed the intraoperative neurophysiological monitoring data and clinical outcomes of 203 patients treated for dorsolumbar spine deformity. The decrease in amplitude was compared with the reduction in the MEP area., Results: In 11 cases, new intraoperative injuries occurred, nine of them were lumbar radiculopathies. Our new criteria, a decrease MEP area of 70%, yielded a sensitivity and specificity of 1, since it detected all the radicular injuries, with no false positive cases. Using a 70% amplitude decrease criteria, we obtained a sensitivity of 0,89 and a specificity of 0,99. A lower threshold (65% amplitude reduction) yielded a higher number of false positives, whereas a higher threshold (75 and 80%) gave rise to a higher number of false negatives., Conclusions: The measurement of the MEP area gave evidence to be more reliable and accurate than the measurement of the amplitude reduction in order to assess and detect intraoperative radicular injuries., Significance: The criterion of decrease of the MEP area has a higher reliability and accuracy in the detection of intraoperative radicular lesions than the amplitude reduction., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Sciatica is a common condition reported to affect over 3% of the UK population at any time and is often caused by a prolapsed intervertebral disc (PID). Although the duration and severity of symptoms can vary, pain persisting beyond 6 weeks is unlikely to recover spontaneously and may require investigation and treatment. Currently, there is no specific care pathway for sciatica in the National Health Service (NHS), and no direct comparison exists between surgical microdiscectomy and transforaminal epidural steroid injection (TFESI). The NERVES (NErve Root block VErsus Surgery) trial aims to address this by comparing clinical and cost-effectiveness of surgical microdiscectomy and TFESI to treat sciatica secondary to a PID., Methods/design: A total of 163 patients were recruited from NHS out-patient clinics across the UK and randomised to either microdiscectomy or TFESI. Adult patients (aged 16-65 years) with sciatic pain endured for between 6 weeks and 12 months are eligible if their symptoms have not been improved by at least one form of conservative (non-operative) treatment and they are willing to provide consent. Patients will be excluded if they present with neurological deficit or have had previous surgery at the same level. The primary outcome is patient-reported disability measured using the Oswestry Disability Questionnaire (ODQ) score at 18 weeks post randomisation and secondary outcomes include disability and pain scales using numerical pain ratings, modified Roland-Morris and Core Outcome Measures Index at 12-weekly intervals, and patient satisfaction at 54 weeks. Cost-effectiveness and quality of life (QOL) will be assessed using the EQ-5D-5 L and self-report cost data at 12-weekly intervals and Hospital Episode Statistics (HES) data. Adverse event data will be collected. Analysis will follow the principle of intention-to-treat., Discussion: NERVES is the first trial to evaluate the comparative clinical and cost-effectiveness of microdiscectomy to local anaesthetic and steroid administered via TFESI. The results of this research may facilitate the development of an evidence-based treatment strategy for patients with sciatica., Trial Registration: ISRCTN, ID: ISRCTN04820368 . Registered on 5 June 2014. EudraCT EudraCT2014-002751-25. Registered on 8 October 2014.

BACKGROUND Surgeons usually transfer the contralateral C7 to the median nerve on the injured side via a nerve graft to recover sensation and movement in a paralyzed hand. The purpose of our study was to determine whether NRG-1 affects the recovery of nerve function in brachial plexus injury after contralateral C7 nerve root transfer in a rat model. MATERIAL AND METHODS An injury model of left brachial plexus and contralateral C7 nerve root transfer was established. Four weeks after the operation, NRG-1 expression was examined by reverse transcription quantitative polymerase chain reaction and Western blot analysis. The diameter rate differences of the healthy limb and affected limb were estimated. The postoperative mass of the left latissimus dorsi, triceps, extensor carpi radialis brevis, and musculus extensor digitorum were examined. The number of nerve fibers and typical area of the affected side were assessed. Postoperative left motor nerve conduction velocity (MNCV) and motor nerve action potential (MNAP) were tested by use of a biological information recording and collecting system. RESULTS Eukaryotic expression plasmid of pcDNA4/myc/A-NRG-1 was successfully constructed, and NRG-1 was overexpressed. Compared with the model group, the NRG-1 group had a lower rate of differences of the limbs; higher mass of left latissimus dorsi, triceps, extensor carpi radialis brevis, and musculus extensor digitorum; more nerve fibers and larger typical area in the affected side, left MNCV, and MNAP; and wider CSA of the left triceps. CONCLUSIONS These results demonstrated that NRG-1 can promote recovery of nerve function in brachial plexus injury after contralateral C7 nerve root transfer in rats.

Background: Spinal cord injury (SCI) is a highly devastating injury with a variety of complications; among them are neurogenic bladder, bowel, and sexual dysfunction. We aimed to evaluate the effect of sacral anterior root stimulation with sacral deafferentation (SARS-SDAF) on neurogenic bladder and sexual dysfunction in a large well-defined spinal cord injury cohort., Methods: In the manner of cross-sectional study, subjects undergone SARS-SDAF between September 1986 and July 2011 answered a questionnaire concerning conditions before and after surgery in the department of Neuro-Urology, Bad Wildungen, Germany., Results: In total 287 of 587 subjects were analyzed. Median age was 49 years (range 19-80), median time from SCI to surgery was 10 years (range 0-49), and from surgery to follow-up 13 years (range 1-25). Of the analyzed subjects, 100% of both gender used SARS for bladder emptying. On the visual analogue scale (VAS) ranging from 0 to 10 (best), satisfaction with SARS-SDAF was 10 concerning bladder emptying, however 5 and 8 regarding sexual performance, for female and male users, respectively. Baseline and follow-up comparison showed a decline in self-intermittent catheterization (p < 0.0001), partial catheterization by attendant (p = 0.0125), complete catheterization and suprapubic catheterization (p < 0.0001), transurethral catheterization (p < 0.0011), and fewer cases of involuntary urine leakage (p < 0.0001)., Conclusions: The SARS-SDAF is a beneficial multi-potential treatment method with simultaneous positive effect on multi-organ dysfunction among SCI subjects.

Aim: To quantify the clinical findings in patients with potential cauda equina syndrome (CES)., Methods: Three domains were selected: bladder function (B), perianal sensation (S) and anal tone/squeeze (T). A quantified score was given to symptoms and signs in each domain., Results: The lowest score in each domain and the lowest sum score (the most severe lesion) is 0. The best sum score is 9 (the normal patient)., Conclusion: TCS can improve the clinical assessment and management of patients with possible CES and improve communication between the doctors who are called upon to assess and treat such patients.

OBJECTIVE Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically been performed at and cephalad to, but not below, the level of SCI. This study was initiated to investigate the validity of 3 proposed concepts regarding the DREZ in SCI central pain: 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through sympathetic nervous system (SNS) pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain-generators. METHODS Three unique patients with both intractable SCI below-level central pain and complete spinal cord transection at the level of SCI were identified. All 3 patients had previously undergone surgical intervention to their spinal cords-only cephalad to the level of spinal cord transection-with either DREZ microcoagulation or cyst shunting, in failed attempts to relieve their SCI below-level central pain. Subsequent to these surgeries, DREZ lesioning of the spinal cord solely caudal to the level of complete spinal cord transection was performed using electrical intramedullary guidance. The follow-up period ranged from 1 1/2 to 11 years. RESULTS All 3 patients in this study had complete or near-complete relief of all below-level neuropathic pain. The analyzed electrical data confirmed and enhanced a previously proposed somatotopic map of SCI below-level DREZ pain generators. CONCLUSIONS The results of this study support the following hypotheses. 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through SNS pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain generators.

Objective: The aim of the study was to compare the effects of mechanical lumbar traction either in the supine or in the prone position with conventional physical therapy (PT) in patients with chronic low back pain and lumbosacral nerve root involvement in terms of disability, pain, and mobility., Design: Participants (N = 125) were randomly assigned to receive 15 sessions of PT with additional mechanical lumbar traction either in the supine position (supine traction group) or in the prone position (prone traction group) or only PT without traction (PT only group). Patients were assessed at baseline and at the end of the PT sessions in terms of disability, pain, and mobility. Disability was assessed using the modified Oswesty Disability Index; pain was assessed using a visual analog scale, and lumbar mobility was assessed using the modified lumbar Schober test., Results: One hundred eighteen patients completed the trial. All groups improved significantly in the Oswesty Disability Index, visual analog scale, and modified lumbar Schober test (P < 0.05). In the between-group analysis, improvements of Oswesty Disability Index and visual analog scale were found significantly better in the prone traction group compared with the PT only group (adjusted P = 0.031 and 0.006, respectively)., Conclusions: Addition of traction in the prone position to other modalities resulted in larger immediate improvements in terms of pain and disability, and the results suggest that when using traction, prone traction might be first choice. Further research is needed to confirm the benefits of lumbar traction in the prone position.

Neurogenic inflammation results from the release of biologically active agents from the peripheral primary afferent terminal. This release reflects the presence of releasable pools of active product and depolarization-exocytotic coupling mechanisms in the distal afferent terminal and serves to alter the physiologic function of innervated organ systems ranging from the skin and meninges to muscle, bone, and viscera. Aside from direct stimulation, this biologically important release from the peripheral afferent terminal can be initiated by antidromic activity arising from five anatomically distinct points of origin: (i) afferent collaterals at the peripheral-target organ level, (ii) afferent collaterals arising proximal to the target organ, (iii) from mid-axon where afferents lacking myelin sheaths (C fibers and others following demyelinating injuries) may display crosstalk and respond to local irritation, (iv) the dorsal root ganglion itself, and (v) the central terminals of the afferent in the dorsal horn where local circuits and bulbospinal projections can initiate the so-called dorsal root reflexes, i.e., antidromic traffic in the sensory afferent.

Chronic injury of limb nerves leading to neuropathic pain affects deep somatic nerves. Here the functional properties of injured afferent fibers in the lateral gastrocnemius-soleus nerve were investigated 20 and 80 days after suturing the central stump of this muscle nerve to the distal stump of the sural nerve in anesthetized rats. Neurophysiological recordings were made from afferent axons identified in either the sciatic nerve (87 A-, 63 C-fibers) or the dorsal root L4/L5 (52 A-, 26 C-fibers) by electrical stimulation of the injured nerve. About 70% of the functionally identified A-fibers had regenerated into skin by 80 days after nerve suture; the remaining A-fibers could be activated only from the injured nerve. In contrast, 93% of the functionally identified C-fibers could only be activated from the injured sural nerve after 80 days. Nearly half of the injured A- (45%) and C-fibers (44%) exhibited ongoing and/or mechanically or thermally evoked activity. Because ~50% of the A- and C-fibers are somatomotor or sympathetic postganglionic axons, respectively, probably all injured muscle afferent A- and C-fibers developed ectopic activity. Ongoing activity was present in 17% of the A- and 46% of the C-fibers. Mechanosensitivity was present in most injured A- (99%) and C-fibers (85%), whereas thermosensitivity was more common in C-fibers (cold 46%, heat 47%) than in A-fibers (cold 18%, heat 12%). Practically all thermosensitive A-fibers and C-fibers were also mechanosensitive. Thus, unlike cutaneous axons, almost all A- and C-fibers afferents in injured muscle nerves demonstrate ectopic activity, even chronically after nerve injury. NEW & NOTEWORTHY After chronic injury of a muscle nerve, allowing the nerve fibers to regenerate to the target tissue, 1) most afferent A-fibers are mechanosensitive and regenerate to the target tissue; 2) ectopic ongoing activity, cold sensitivity, and heat sensitivity significantly decrease with time after injury in A-afferents; 3) most afferent C-fibers do not regenerate to the target tissue; and 4) injured C-afferents maintain the patterns of ectopic discharge properties they already show soon after nerve injury.

Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared with healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18 kDa translocator protein, in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord. These elevations demonstrated a pattern of spatial specificity correlating with the patients' clinical presentation, as they were observed in the neuroforamen ipsilateral to the symptomatic leg (compared with both contralateral neuroforamen in the same patients as well as to healthy controls) and in the most caudal spinal cord segments, which are known to process sensory information from the lumbosacral nerve roots affected in these patients (compared with more superior segments). Furthermore, the neuroforaminal translocator protein signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.

Aims: To investigate the feasibility of restoring bladder function and prevention of renal deterioration by neurorrhaphy in rats with neurogenic bladder (NB)., Methods: Forty-two rats were assigned to the end-to-side nerve coaptation group (ECG, n = 16), no nerve coaptation group (NCG, n = 16), and control group (CG, n = 10). In the ECG, the left ventral root (VR) and dorsal root (DR) of L6 and S1 were transected, and the distal stump of L6VR was sutured to the lateral face of L4VR. In the NCG, the left VR and DR of L6 and S1 were transected, but coaptation was not performed. In the CG, no operation was performed. Nerve regeneration, bladder function, and renal function were evaluated by FluoroGold (FG) retrograde tract tracing, cystometry, electrical stimulation, MRI, histology and biochemical assays., Results: In the ECG, FG-labeled neurons were observed in the left ventral horn of L4 spinal cord. There was a significant increase in intravesical pressure upon stimulation of the left L4VR proximal to the coaptation. Maximum cystometric capacity, post-void residual urine, bladder compliance and weight, serum creatinine, blood urea nitrogen, and fibrotic area of bladder and kidney were lower in the ECG than in the NCG, but higher than the CG. Hydronephrosis was noticed in ECG and NCG rats. Maximum detrusor voiding pressure was higher in the ECG and CG than in the NCG., Conclusions: End-to-side neurorrhaphy is a useful method for restoring bladder function and preventing renal injury in rats with NB., (© 2017 Wiley Periodicals, Inc.)

Background: Replantation of the avulsed nerve root has been proposed for the treatment of severe brachial plexus injury for several decades. However, due to the complexity of the technique and limited functional improvement, practical applications are yet to be implemented., Objective: In the present study, we investigated the effect of pretreatment with resveratrol on nerve autografts used for replantation surgery in a rat model of nerve root avulsion., Methods: Resveratrol pretreatment was performed using an explant culture technique. Two surgical procedures were performed. During the first surgery, Sprague-Dawley rats were subjected to left C6 nerve root avulsion, and nerves were harvested for autografting. The harvested grafts were explant-cultured for 1 week. A second procedure was performed to replant the C6 nerve root using the explant-cultured nerve graft 1 week after the first procedure. Histological and immunohistochemical analyses were performed 8 weeks after the second procedure. We first compared findings between explant-cultured nerve grafts and fresh nerve grafts, following which we compared findings between explant-cultured grafts pretreated with and without resveratrol. Changes induced within nerve grafts by 1 week of explant culture with or without resveratrol were investigated in vitro., Results: There was no significant difference in outcomes between 1 week-explant-cultured and fresh nerve grafts. Addition of resveratrol to the explant culture medium resulted in a significant increase in the number and myelin thickness of regenerated axons, and in the number of regenerating motor neurons in the C6 spinal cord segment. In vitro analyses revealed that nerve grafts pretreated with resveratrol exhibited significant increases in glial cell line-derived neurotrophic factor (GDNF) expression and the number of dedifferentiated Schwann cells., Conclusions: Resveratrol may promote axonal regeneration following replantation surgery for the treatment of nerve root avulsion injury; however, further studies are required to verify these findings in humans.

Aims: Lumbar to sacral rerouting surgery can potentially allow voiding via a skin-central nervous system-bladder reflex pathway. Here, we assessed if this surgery was effective in treating neurogenic bladder dysfunction/sphincter in felines., Methods: Eight cats underwent spinal cord transection (SCT) at thoracic level 10/11. Unilateral L7 to S1 ventral root anastomosis was performed 1 month later in six cats. Two cats served as transection-only controls. Electrical and manual stimulation of L6-S1 dermatomes, and urodynamics were performed at 3, 5, 7, and 9/10 months post transection. At 9/10 months, cats were also evaluated by direct electrophysiological testing of anastomosed roots with urodynamics, then tissue collection and examination of the root anastomosis site and lumbosacral cord ventral horns for cells retrogradely labeled from tracer dye injected 2 weeks earlier into the bladder wall., Results: At 9/10 months, four of six rerouted cats exhibited increased detrusor pressure provoked by cutaneous stimulation, one cat bilaterally. Two cats presented with a voiding stream after ipsilateral cutaneous stimulation at 7 and 9 months. All six rerouted animals showed regrowth of axons from the L7 ventral horn to the bladder, although some aberrant axonal regrowth was also observed., Conclusion: L7 to S1 ventral root rerouting below the level of SCT showed successful axonal regrowth to the bladder from the L7 spinal cord segment in all rerouted animals, and induced increased detrusor pressure response to cutaneous stimulation in a subset. This feasibility study paves the way for future animal studies for bladder reinnervation., (© 2018 Wiley Periodicals, Inc.)

Purpose: To perform a synthesis of articles addressing the role of stretching on roots in the pathophysiology of radiculopathy., Methods: Review of relevant articles on this topic available in the PubMed database., Results: An intraoperative microscopy study of patients with sciatica showed that in all patients the hernia was adherent to the dura mater of nerve roots. During the SLR (Lasègue's) test, the limitation of nerve root movement occurs by periradicular adhesive tissue, and temporary ischemic changes in the nerve root induced by the root stretching cause transient conduction disturbances. Spinal roots are more frail than peripheral nerves, and other mechanical stresses than root compression can also induce radiculopathy, especially if they also impair intraradicular blood flow, or the function of the arachnoid villi intimately related to radicular veins. For instance arachnoiditis, the lack of peridural fat around the thecal sac, and epidural fibrosis following surgery, can all promote sciatica, especially in patients whose sciatic trunks also stick to piriformis or internus obturator muscles. Indeed, stretching of roots is greatly increased by adherence at two levels., Conclusions: As excessive traction of nerve roots is not shown by imaging, many physicians have unlearned to think in terms of microscopic and physiologic changes, although nerve root compression in the lumbar MRI is lacking in more than 10% of patients with sciatica. It should be reminded that, while compression of a spinal nerve root implies stretching of this root, the reverse is not true: stretching of some roots can occur without any visible compression., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: We designed this study using super-selective intraoperative cervical nerve root stimulation aiming to support decision making about complete or partial contralateral C7 (cC7) nerve root transfer in patients with multiple cervical root avulsion injury., Methods: Super-selective intraoperative stimulations of anterior, lateral, medial and posterior aspect of C5-C8 nerve roots were performed. Compound muscle action potentials (CMAP) were recorded in the lateral part of the deltoid (DM), long head of biceps brachii (BCM), brachioradial (BRM), long head of triceps brachii (TCM), and extensor digitorum communis (EDC) muscle. Muscle strength was documented immediately after cC7 transfer procedures and on scheduled follow-up visits according to the Medical Research Council (MRC) scale., Results: In the DM, stimulation of the posterior aspect of C5 resulted in the largest CMAP amplitudes (2.0 mV ± 1.9; 80% ± 28.3). The BCM CMAPs induced by the different aspects of C6 all revealed homogenous stimulation results. Stimulation of the lateral aspect of C7 induced the largest amplitude of TCM CMAPs (1.3 mV ± 1.0; 67.1% ± 43.3). CMAP amplitudes of individual muscles and individual contributions of cervical nerve roots to the TCM varied between subjects. Overall donor side morbidity was low, no permanent motor deficit occurred., Conclusion: A super-selective intraoperative cervical nerve root stimulation may help minimize donor side morbidity in transfer procedures. Individual differences of cervical nerve root innervation pattern need to be addressed in future electrophysiological studies., Significance: Our study outlines individual differences of cervical nerve root innervation pattern., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: The aims of this exploratory study were (1) to develop a standardized objective electrophysiological technique with laser-evoked potentials to assess dorsal root damage quantitatively and (2) to correlate these LEP measures with clinical parameters and sensory abnormalities (QST) in the affected dermatome., Methods: Thirty-eight patients with painful radiculopathy and 20 healthy subjects were investigated with LEP recorded from the affected dermatome and control areas as well as with quantitative sensory testing. Questionnaires evaluating severity and functionality were applied., Results: On average, LEP amplitudes and latencies from the affected dermatomes did not differ from the contralateral control side. In patients with left L5 radiculopathy (more severely affected) the N2 latency was longer and the amplitudes reduced., Conclusions: The N2P2 amplitude correlated with pinprick evoked sensations in QST. The N2 latency from the affected dermatome correlates with pain intensity, chronicity, clinical severity and with a decrease of physical function., Significance: An increase in N2-latency indicates a more pronounced nerve root damage, which is associated with a decrease of function and an increase of severity and pain. LEP amplitudes are associated with the functional status of the nociceptive system and may distinguish between degeneration of neuronal systems and central sensitization processes., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Hyperexcitability is hypothesized to contribute to the degeneration of spinal motoneurons (MNs) in amyotrophic lateral sclerosis (ALS). Studies, thus far, have not linked hyperexcitability to the intrinsic properties of MNs in the adult ALS mouse model with the G93A-mutated SOD1 protein (mSOD1 G93A ). In this study, we obtained two types of measurements: ventral root recordings to assess motor output and intracellular recordings to assess synaptic properties of individual MNs. All studies were carried out in an in vitro preparation of the sacral spinal cords of mSOD1 G93A mice and their non-transgenic (NT) littermates, both in the age range of 50-90days. Ventral root recordings revealed that maximum compound action potentials (coAPs) evoked by a short-train stimulation of corresponding dorsal roots were similar between the two types of mice. Although the progressive depression of coAPs was present during the train stimulation in all recordings, the coAP depression in mSOD1 G93A mice was to a lesser extent, which suggests an increased firing tendency in mSOD1 G93A MNs. Intracellular recordings showed no changes in fast excitatory postsynaptic potentials (EPSPs) in mSOD1 G93A MNs. However, recording did show that oscillating EPSPs (oEPSPs) were induced by poly-EPSPs at a higher frequency and by less-intense electrical stimulation in mSOD1 G93A MNs. These oEPSPs were dependent upon the activities of spinal network and N-methyl-d-aspartate receptors (NMDARs), and were subjected to riluzole modulation. Taken together, these findings revealed abnormal electrophysiology in mSOD1 G93A MNs that could underlie ALS excitotoxicity., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Chronic pain is one of the most reported health problems in patients suffering from spinal cord injuries and is described by the patients as one of the most burdensome sequelae of paraplegia. Various types of pain, such as nociceptive, neuropathic and other types of pain can occur. In addition, multiple pathophysiological mechanisms based on the biopsychosocial pain model play a role in the origins of the pain. These aspects necessitate a multimodal pain management approach in this patient group. This article presents an overview of the occurrence, importance and pathophysiology of chronic pain following spinal cord injury as well as diagnostic and therapeutic approaches.

The "gold standard" treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.

Spinal Dorsal Ramus Mediated Back Pain is the second most frequently described condition (the first one being Lumbar Facet Syndrome) originating from pathology involving posterior branches of lumbar spinal nerves. Spinal Dorsal Ramus Mediated Back Pain was described as "thoracolumbar junction syndrome" by Maigne in 1989. As a rule, Spinal Dorsal Ramus Mediated Back Pain presents unilaterally within posterior branches at the levels Th11-12 and L1-2. The pain is triggered by extension and/or rotation. Typical symptoms include pain that may radiate towards the gluteal area and posterior iliac crest and does not cross the body midline. Clinical symptoms may correlate with the area supplied by the whole spinal nerve of the given segment, including both the posterior and anterior branch. For this reason, patients may report not only low back pain, but also pseudovisceral pain in the hypogastric area, false sciatic neuralgia, tenderness of the pubic symphysis and hypersensitivity of the intestines. The above symptoms may lead to diagnostic difficulties. Diagnostic work-up may benefit from performance of the Kibler Fold Test to determine sensitivity of the tissues surrounding the iliac crest. Patients with Spinal Dorsal Ramus Mediated Back Pain respond well to manual manipulative techniques if these are delivered in a technically correct manner and address the appropriate segment. A recommended approach for patients with absolute contraindications to manipulation, i.e. advanced osteoporosis or osteogenesis imperfecta, is a block of the po-sterior branch of the spinal nerve involved.

Aims: To investigate the long-term course of the detrusor pressure during sacral anterior root stimulation in spinal cord injury (SCI) patients., Methods: Retrospective evaluation of 111 patients who had undergone sacral deafferentation and implantation of an anterior root stimulator at a single SCI rehabilitation center with a minimum follow-up time of 5 years., Results: The median follow-up time was 11.7 years (range 5.0-24.9 years). The maximum detrusor pressure (Pdet&#95;max) during stimulation was higher in men compared to women (P = 0.0004) and decreased over time (P = 0.0006). However, there were no significant (P ≥ 0.06) differences in the median Pdet&#95;max during stimulation between the first measurement time point and any follow-up time point. The Pdet&#95;max during stimulation decreased from 62 cmH 2 O (95%CI 57-73 cmH 2 O) to 53 cmH 2 O (95%CI 47-69 cmH 2 O) (P = 0.9). The time had also a significant effect on Pdet&#95;max during the storage phase (P < 0.0001) and bladder compliance (P = 0.0007). The Pdet&#95;max during the storage phase decreased, whereas bladder compliance increased during the follow-up period. There were no significant (P ≥ 0.1) changes over time in bladder capacity, the number of daily stimulations and the residual urine volume after voiding., Conclusions: The detrusor pressure during sacral anterior root stimulation decreases over time in SCI individuals. However, the changes do not seem to be clinically relevant during the first decade after surgery., (© 2016 Wiley Periodicals, Inc.)