Skin and not dorsal root stimulation reduces hypertonus in thoracic motor complete spinal cord injury: a single case report.

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.

Sacral Anterior Root Stimulation and Visceral Function Outcomes in Spinal Cord Injury-A Systematic Review of the Literature Over Four Decades.

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.

Long-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion.

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.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: correlation between histological changes and nerve evoked contractions.

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.

Chronic immune polyradiculopathies: Three clinical variants of one disease?

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.

The eight cervical nerve and its role in tinnitus.

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.

Upper Cervical Nerves Can Induce Tinnitus.

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.

The comparison of MRN, electrophysiology and progression among typical CIDP and atypical CIDP subtypes.

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.

Pilot prospective open-label one-arm trial investigating intrathecal Adenosine in neuropathic pain after lumbar discectomy.

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.

Neurostimulation in neurogenic patients.

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.

Bursting interneurons in the deep dorsal horn develop increased excitability and sensitivity to serotonin after chronic spinal injury.

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-HT1B/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).

Motor unit number index in quantitatively assessing motor root lesions and monitoring treatment outcomes in patients with lumbosacral radiculopathy.

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.

Electrodiagnostic characteristics of upper lumbar stenosis: Discrepancy between neurological and structural levels.

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.

Dynamic mapping of the corticospinal tract in open cordotomy and myelomeningocele surgery.

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.

Posteroanterior cervical transcutaneous spinal stimulation targets ventral and dorsal nerve roots.

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.

Multimodal intraoperative monitoring during surgical correction of scoliosis to avoid neurologic damage.

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.

Surgical Outcomes After Anterior Controllable Antedisplacement and Fusion Compared with Single Open-Door Laminoplasty: Preliminary Analysis of Postoperative Changes of Spinal Cord Displacements on T2-Weighted Magnetic Resonance Imaging.

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.

Theory of Bowstring Disease: Diagnosis and Treatment Bowstring Disease.

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.

LINGO-1 shRNA Loaded by Pluronic F-127 Promotes Functional Recovery After Ventral Root Avulsion.

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.