Abstract: Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain and paresthesia (sciatica). While traditionally considered the result of mechanical compression of the dorsal root ganglion (DRG) and/or spinal nerve root, recent studies implicate pro-inflammatory mediators released from or evoked by NP, a possibility that was presently investigated. Single-unit recordings were made from L5 wide dynamic range dorsal horn neurons in pentobarbital-anesthetized rats. Autologous NP was harvested from a coccygeal disc and placed onto the exposed L5 DRG. A control group had subcutaneous adipose tissue or saline placed similarly. To test involvement of tumor necrosis factor-alpha (TNF-alpha), a third group received autologous NP plus local soluble TNF-alpha receptor type 1 (0.013 microg) which binds TNF-alpha to prevent its action. In each group, neuronal responses to graded heat (38-50 degrees C) and mechanical (von Frey filaments 4-76 g) stimuli were recorded prior to and at three successive hourly intervals following each treatment. Responses to noxious heat and mechanical stimuli were significantly enhanced 1 h post-NP and remained elevated thereafter. Thermally and mechanically evoked responses were not significantly affected in control rats or those treated with NP + soluble TNF-alpha receptor type 1. These results indicate that sensitization of nociceptive spinal neuronal responses develops quickly following exposure of the DRG to NP, and that TNF-alpha is involved. This electrophysiological model of herniated NP may prove useful in further characterizing the role of inflammatory mediators in hyperalgesia and allodynia resulting from lumbar disc herniation.

Abstract: Study Design. This study analyzed the effects of autografted nucleus pulposus on nerve root axon morphology, neurophysiologic function, and sodium channel expression. Objectives. To investigate the chronic effects of the epidural implantation of nucleus pulposus on nerve root morphology, neural activity, ectopic discharge, mechanosensitivity, and sodium channel expression. Summary of Background Data. It has been reported that ectopic discharges were recorded antidromically from sural nerve on compressing nucleus pulposus exposed spinal nerves. However, it is not clear what the effects of nucleus pulposus are on ectopic discharges recorded directly from the spinal nerve roots. It is also not clear what the effects of nucleus pulposus are on the threshold pressure to provoke ectopic discharges in the spinal nerves. Sodium channel content increases in remodeling axons after nerve injury, but it is not clear what the effects of nucleus pulposus are on sodium channel expression in spinal nerve. Methods. Forty-six male Sprague-Dawley rats were used, 20 in a nucleus pulposus-implanted group, 18 in a fat-implanted group, and 8 in a normal group. Fresh autografted nucleus pulposus or fat tissue was implanted into the dorsal epidural space at the L4 –L5 disc level. On the 7th, 21st, or 42nd day, neurophysiologic recordings were made to determine nerve root response to compression. Nerve roots were then harvested to determine sodium channel protein concentration and histologic changes in the nerve root. The correlations between sodium channel density and neural activity and mechanosensitivity of dorsal root were analyzed statistically. Results. Ectopic discharge rate was higher in nucleus pulposus 7-day group. Threshold pressure to evoke ectopic discharges was lower in the nucleus pulposus 7-day group, and higher in the nucleus pulposus 42-day group compared to the normal group. Sodium channel protein density increased in the nucleus pulposus 7-day and nucleus pulposus 21-day group compared to normal nerve. Sodium channel density changes were not correlated to threshold pressure. Ectopic discharge rate increased with increase of sodium channel density in the nerve roots. The number of axons with neuropathy increased in the nucleus pulposus 7-day and 21-day groups. Conclusions. Acute exposure of nerve root to nucleus pulposus resulted in increased number of axons with neuropathy, higher intensity of ectopic discharges on compression, and nerve mechanosensitization. Chronic exposure resulted in mechanical desensitization. Changes of sodium channel density were correlated to ectopic discharge rate. [Key words: nucleus pulposus, nerve root, neurophysiology, mechanosensitivity, sodium channel protein, axonal histology, Schmidt-Lantenman incisure] Spine 2004;29:17–25

Abstract: STUDY DESIGN: Distribution and appearance of tumor necrosis factor-alpha (TNF-alpha) in the dorsal root ganglion (DRG) exposed to experimental disc herniation were investigated using an immunohistochemical method in rats. OBJECTIVES: To study the distribution and appearance of TNF-alpha in the DRG following experimental disc herniation in rats. SUMMARY OF BACKGROUND DATA: Nucleus pulposus in the epidural space induces spinal nerve root injury not only by mechanical but also chemical mechanisms. Cytokines may play a key role in the chemical damage. There is, however, no report on the distribution and appearance of TNF-alpha in the DRG exposed to nucleus pulposus. METHODS: Nucleus pulposus from the discs was smeared on the glass slides and processed for immunohistochemistry by the avidin-biotinylated peroxidase complex technique using rabbit antisera to TNF-alpha in rats. A herniation of the nucleus pulposus was made by incision of the L4-L5 disc in rats. The L4 and L5 DRGs were resected 1, 3, 7, 14, and 21 days after surgery. The specimens were processed for immunohistochemistry using rabbit antisera to TNF-alpha. The TNF-alpha-positive cells were observed and counted using light microscopy. Distribution of the TNF-alpha products was compared on each day after surgery. RESULTS: A positive staining was seen in the cell bodies and in the matrix between the cells in the smeared nucleus pulposus. In the L4 DRG sections, the number of positive cells was significantly higher in the disc incision group than in the sham group at 1, 3, 7, and 14 days after surgery (P < 0.05). The positive cells showed a decrease in number day by day after surgery. On the contrary, in the L5 DRG, only a few positive cells were observed in the disc incision group after surgery. There was no statistically significant difference between disc incision and the sham groups at each day after surgery for the L5 DRGs. CONCLUSIONS: The immunoreactivity of TNF-alpha in the DRG directly exposed to nucleus pulposus increases during 2 weeks. A collapse of the positive cells was seen in the DRG directly exposed to the nucleus pulposus.

Abstract: STUDY DESIGN An analysis of pathologic changes after different degrees of cauda equina compression OBJECTIVES To explore the association between the degree of the cauda equina compression and the extent of pathologic change, expression of tumor necrosis factor (TNF-alpha), and neuropathic pain To compare with distal nerve compression injury SUMMARY OF BACKGROUND DATA Compression of the cauda equina reduces blood flow in compressed nerve roots and causes TNF-alpha expression and neuropathological change In peripheral nerve, expression of TNF-alpha in Schwann cells is associated with primary demyelination without pain while TNF-alpha expression by macrophages is associated with axonal (Wallerian) degeneration and pain METHODS Two square-shaped pieces of silicon were placed into the fourth and sixth epidural space in rats Various sized silicon was used in each group (mild, moderate, and strong compression groups), while no silicon was used in the sham-operated group Mechanical allodynia was determined by the von Frey test Comparisons of the number of TNF-alpha- and apoptosis-positive cells were made using immunohistochemistry RESULTS There was no significant mechanical allodynia observed in any group Some nerve roots showed demyelination following mild cauda equina compression Axonal degeneration was observed in the moderate and strong cauda equina compression groups TNF-alpha-immunoreactive cells were increased in all compression groups Apoptosis of dorsal root ganglion cells was less than apoptosis in the spinal cord CONCLUSION Mild cauda equina compression induces TNF-alpha expression and demyelination Moderate and strong cauda equina compression induces TNF-alpha expression and degeneration associated with macrophage invasion Neither demyelination nor degeneration in the cauda equina induced mechanical allodynia Nerve lesions proximal to the dorsal root ganglion do not produce significant mechanical allodynia Dorsal root ganglion apoptosis may be important for pain

Abstract: BACKGROUND Radicular pain is caused by irritation of the sensory root or dorsal root ganglion of a spinal nerve. The irritation causes ectopic nerve impulses perceived as pain in the distribution of the axon. The pathophysiology is more than just mass effect: it is a combination of compression sensitising the nerve root to mechanical stimulation, stretching, and a chemically mediated noncellular inflammatory reaction. OBJECTIVE This article discusses the clinical features, assessment and management of lumbar radicular pain (LRP). DISCUSSION Lumbar radicular pain is sharp, shooting or lancinating, and is typically felt as a narrow band of pain down the length of the leg, both superficially and deep. It may be associated with radiculopathy (objective sensory and/or motor dysfunction as a result of conduction block) and may coexist with spinal or somatic referred pain. In more than 50% of cases, LRP settles with simple analgesics. Significant and lasting pain relief can be achieved with transforaminal epidural steroid injection. Surgery is indicated for those patients with progressive neurological deficits or severe LRP refractory to conservative measures.

Abstract: STUDY DESIGN: The effect of infliximab, a chimeric monoclonal antibody to TNF-alpha, on induction of brain-derived neurotrophic factor (BDNF) was examined using an experimental herniated nucleus pulposus (NP) model. OBJECTIVES: To investigate whether treatment of infliximab could attenuate an induction of BDNF, which functions as a modulator of pain, following NP application to the nerve root. SUMMARY OF BACKGROUND DATA: Evidence from basic scientific studies proposes that TNF-alpha is involved in the development of NP-induced nerve injuries. However, the therapeutic mechanisms of infliximab against pain have not been elucidated experimentally. METHODS: Twenty rats were used in this study. In the test groups, the animals underwent application of NP to the L4 nerve roots and received a single systemic (intraperitoneal) injection of infliximab at the time of surgery (Infli-0 group, n = 5) or at 1 day after operation (Infli-1 group, n = 5). As a control treatment, sterile water was administered intraperitoneally to 5 rats with NP application (NP group) and to 5 sham-operated rats (sham group). On day 3 after surgery, the L4 dorsal root ganglion (DRG) and L4 spinal segment were harvested and assessed regarding BDNF immunoreactivity. RESULTS.: Application of NP induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (P < 0.01). Infliximab treatment in the Infli-0 and Infli-1 groups reduced the BDNF induction in both DRG and spinal cord (P < 0.05). CONCLUSION: These findings indicate that infliximab attenuates the elevated BDNF levels induced by NP. The present study therefore further indicates the importance of TNF-alpha in sciatica due to disc herniation and the possible therapeutic use of a TNF-alpha inhibitor for this condition.

Abstract: PURPOSE: To examine whether magnetic resonance (MR) imaging findings of the cervical spine can predict pain relief after selective computed tomography (CT)-guided nerve root block and thus assist in the appropriate selection of patients who are suitable for this procedure. MATERIALS AND METHODS: Sixty consecutive patients with cervical radicular pain were examined with MR imaging and then treated with CT-guided cervical nerve root blocks (CNRBs). Various MR imaging findings were assessed and compared in terms of associated pain relief after CNRB. Pain relief was graded (0%–100%) by using a visual analogue scale (VAS). The relationship between MR imaging findings and level of pain relief was tested by using Mann-Whitney U and Kruskal-Wallis tests. RESULTS: The mean percentage of pain reduction at VAS grading was 46%. There was a significant relationship between pain relief level and both location of disk herniation (mean pain reductions of 41% at median or mediolateral locations and 64% at foraminal locati...

Abstract: Objective To investigate the outcomes resulting from the use of fluoroscopically guided therapeutic selective nerve root block in the nonsurgical treatment of traumatically induced cervical spondylotic radicular pain. Design Retrospective study with independent clinical review. A total of 15 patients who met specific physical examination or electrodiagnostic criteria and failed to improve clinically after at least 4 wks of physical therapy were included. Each patient demonstrated a positive response to a fluoroscopically guided cervical selective nerve root block. Therapeutic selective nerve root blocks were administered in conjunction with physical therapy. Outcome measures included visual analog scale pain scores, employment status, medication usage, and patient satisfaction. Results Patients' symptom duration before diagnostic injection averaged 13.0 mos. An average of 3.7 therapeutic injections were administered. Follow-up data collection transpired at an average of 20.7 mos after discharge from treatment. An overall good or excellent outcome was observed in three patients (20.0%). Among those treated without surgery, a significant reduction (P = 0.0313) in pain score was observed at the time of follow-up. Six patients (40.0%) proceeded to surgery. Conclusions These initial and preliminary findings do not support the use of therapeutic selective nerve root block in the treatment of this challenging patient population with traumatically induced spondylotic radicular pain.

Abstract: This 9-year-old boy sustained a complete right-sided C5–T1 brachial plexus avulsion injury in a motorcycle accident. He underwent surgery 4 weeks after the accident. The motor-related nerve roots in all parts of the avulsed brachial plexus were reconnected to the spinal cord by reimplantation of peripheral nerve grafts. Recovery in the proximal part of the arm started 8 to 10 months later. Motor function was restored throughout the arm and also in the intrinsic muscles of the hand by 2 years postoperatively. The initial severe excruciating pain, typical after nerve root avulsions, disappeared completely with motor recovery. The authors observed good recruitment of regenerated motor units in all parts of the arm, but there were cocontractions. Transcranial magnetic stimulation produced response in all muscles, with prolonged latency and smaller amplitude compared with the intact side. There was inspiration-evoked muscle activity in proximal arm muscles—that is, the so-called “breathing arm” phenomenon. The issues of nerve regeneration after intraspinal reimplantation in a young individual, as well as plasticity and associated pain, are discussed. To the best of the authors’ knowledge, the present case demonstrates, for the first time, that spinal cord surgery can restore hand function after a complete brachial plexus avulsion injury.

Abstract: Study design: Intercostal nerve to spinal nerve root anastomosis in chronic spine-injured patients. Objectives: To analyze the effectiveness of neurogenic bladder reinnervation in spinal cord-injured patients through artificial creation of sprouting (intercostal nerve to spinal nerve root anastomosis). Setting: Center of Neurosurgery, Moscow, Russia. Operations were performed by Professor A Livshits. (At present, Professor A Livshits is working at the Spinal Care Unit, Meir General Hospital, Kfar Saba, Israel.) Methods: A total of 11 patients with spinal cord injury of the L1 level were operated on in the late (chronic) stage. The neurological status and urodynamics were investigated before and 12 months after operation. A laminectomy from T11 to L3 was performed. Next, a neurolysis of the 11th and 12th intercostal nerves was carried out, at a distance of 20–21 cm, and transferred to the vertebral canal. The S2–S3 roots were then cut in their proximal portion and anastomosed end-to-end to the intercostal nerves. The results of urodynamic studies were calculated by the Wilcoxon signed rank test for comparison before and 12 months after operation. Results of urodynamic studies: Bladder capacity (ml) before operation – 489±79, after operation – 350±39, urine volume (ml) before – 18.2±17, after – 306.4±39.8, residual urine (ml) before – 459±99.4, after – 50±11.8. Detrusor tone (rel. units) before – 0.6±1.5, after 1.2±0.2; voiding pressure (cmH2O) before – 4.4±5.2, after – 30.5±4.9. Force of detrusor contraction before – 5±5.8, after – 32.8±5.5. Sphincter resistance (cmH2O) before – 6.5±3.8, after – 21.1±4.2. Significant improvements in bladder function were observed during the 10th to 12th postoperative months. Restoration of reflex voiding occurred in all patients; in eight of the 11 paresthesic in the groin and scrotum and reappearance of the bulbocavernous, anal and cremasteric reflexes were noted. Conclusion: These results suggest that a restitutive process occurs in the bladder under novel conditions of its nerve supply provided by the intercostal nerve and by new connections established between it and the bladder nerves. Spinal cord lesions that might benefit from nerve crossover surgery would be located at the conus, so functional intercostal nerves could be connected to sacral roots to bypass the injury in an attempt to restore central connections to the bladder.

Abstract: Nerve root anomalies are frequently underrecognized on advanced imaging studies and may account for some percentage of failed spinal surgical procedures. The conjoined nerve root represents the most common nerve root anomaly. It is a well-known cause of false-positive readings for bulging and herniated disks in patients with purely axial neuroimaging studies. A retrospective evaluation of consecutive microsurgical lumbar diskectomies in 80 patients during a 5-year period was undertaken. A total of four patients (5%) were found intraoperatively to have evidence of a conjoined nerve root by the classification of Neidre. None was diagnosed preoperatively. Coronal magnetic resonance imaging offers the best means of visualizing a conjoined nerve root. The chance for a successful operation can be significantly enhanced if the surgeon is prepared to encounter this pathology.

Abstract: Functional recovery after large excision of dorsal roots is absent because of both the limited regeneration capacity of the transected root, and the inability of regenerating sensory fibers to traverse the dorsal root entry zone. In this study, bioresorbable guidance conduits were used to repair 6-mm dorsal root lesion gaps in rats, while neurotrophin-encoding adenoviruses were used to elicit regeneration into the spinal cord. Polyester conduits with or without microfilament bundles were implanted between the transected ends of lumbar dorsal roots. Four weeks later, adenoviruses encoding NGF or GFP were injected into the spinal cord along the entry zone of the damaged dorsal roots. Eight weeks after injury, nerve regeneration was observed through both types of implants, but those containing microfilaments supported more robust regeneration of calcitonin gene-related peptide (CGRP)-positive nociceptive axons. NGF overexpression induced extensive regeneration of CGRP(+) fibers into the spinal cord from implants showing nerve repair. Animals that received conduits containing microfilaments combined with spinal NGF virus injections showed the greatest recovery in nociceptive function, approaching a normal level by 7-8 weeks. This recovery was reversed by recutting the dorsal root through the centre of the conduit, demonstrating that regeneration through the implant, and not sprouting of intact spinal fibers, restored sensory function. This study demonstrates that a combination of PNS guidance conduits and CNS neurotrophin therapy can promote regeneration and restoration of sensory function after severe dorsal root injury.

Abstract: There is much evidence supporting the hypothesis that magnitude of nerve root mechanical injury affects the nature of the physiological responses which can contribute to pain in lumbar radiculopathy. Specifically, injury magnitude has been shown to modulate behavioral hypersensitivity responses in animal models of radiculopathy. However, no study has determined the mechanical deformation thresholds for initiation and maintenance of the behavioral sensitivity in these models. Therefore, it was the purpose of this study to quantify the effects of mechanical and chemical contributions at injury on behavioral outcomes and to determine mechanical thresholds for pain onset and persistence. Male Holtzman rats received either a silk or chromic gut ligation of the L5 nerve roots, a sham exposure of the nerve roots, or a chromic exposure in which no mechanical deformation was applied but chromic gut material was placed on the roots. Using image analysis, nerve root radial strains were estimated at the time of injury. Behavioral hypersensitivity was assessed by measuring mechanical allodynia continuously throughout the study. Chromic gut ligations produced allodynia responses for nerve root strains at two-thirds of the magnitudes of those strains which produced the corresponding behaviors for silk ligation. Thresholds for nerve root compression producing the onset (8.4%) and persistence of pain (17.4%‐22.2%) were determined for silk ligation in this lumbar radiculopathy model. Such mechanical thresholds for behavioral sensitivity in a painful radiculopathy model begin to provide biomechanical data which may have utility in broader experimental and computational models for relating injury biomechanics and physiologic responses of pain. @DOI: 10.1115/1.1695571#

Abstract: The hypoglossal nerve is used classically in salvage of facial paralyses in the absence of spontaneous recovery. A variety of ways of transferring and suturing the hypoglossal nerve to the distal segment of the facial nerve have been reported. In order to determine which mode of reconstruction is the best for neurotisation of the facial nerve, the caliber of the hypoglossal nerve was studied in ten subjects at the level of proximal and distal parts of the trunk and the cervical loop. The fascicular surface area of the cervical branch is inadequate for use. The distal extremity of the hypoglossal nerve has an ideal caliber to be sutured to the facial nerve trunk and the proximal part is large enough to allow partial harvesting of the hypoglossal nerve for neurotisation of the facial nerve.

Abstract: Background: C1 and C2 nerve sheath tumors (NST) are unique in presentation, relationship to neighbouring structures and surgical approaches when compared to their counterparts in other regions of the spine. Aim: The strategies involved in the surgery for C1-C2 NST are discussed Setting and Design: Retrospective study. Methods: 21 patients with C1 (n=6) and C2 (n=15) NST were operated based on their position with respect to the cord i.e. anterior (4), anterolateral (10), posterolateral (5), and posterior (2). The tumors had extra- and intradural components in 20 patients; while in one, the tumor was purely intradural. The operative approaches included the extreme lateral transcondylar approach (3); laminectomy with partial facetectomy (5); laminectomy (11); and, suboccipital craniectomy and laminectomy (2). Results: Total excision was performed in 13 patients; while in 7, a partial extraspinal component, and in 1, a small intradural component were left, in situ. Thirteen patients showed improvement by one or more grades in the Harsh myelopathy score; 2 patients with normal power had significant decrease in spasticity; while 5 maintained their grade. One poor-grade patient succumbed to septicemia. Conclusions: C1-C2 NST may have exuberant growth due to the capacious spinal canal and the absence of a “true” intervertebral foramen at this level. Surgical approaches are determined by its relationship to the cord . A “T incision” on the dura, the partial drilling of the facets, sectioning of the denticulate ligament, rotating the operating table 15 to 30 degrees, and at times sectioning the posterior nerve roots are all useful adjuncts for facilitating access.

Abstract: After facial nerve trauma, aberrant regeneration is associated with synkinesis. Animal models of mechanical nerve guides or reparative cell transplants at the site of a lesion have not been shown to improve disorganized regeneration. We examined whether this is because regenerating axons become disorganized throughout the length of the nerve and not only at the site of the lesion. In rats (n = 12), retrograde fluorescent tracer techniques were used to establish that most of the temporal branch fibres were carried in the superior half of the facial nerve trunk. In two further groups of rats (n = 24) a complete proximal facial nerve lesion was made, and the nerve immediately repaired by suture. After 4 weeks, at a second operation, the superior half of the facial nerve trunk was cut, either proximal or distal to the original lesion, and retrograde tracers were applied to distal branches of the nerve. It was possible to localize the points at which regenerating fibres became aberrant in their course by study...

Abstract: Amalignant peripheral nerve-sheath tumour developed in the right S1 nerve root in a man aged 30 causing back pain and sciatica. CT and MRI revealed a destructive tumour of the sacrum invading the retroperitoneal space. The tumour was not resectable with an adequate margin. Chemotherapy, consisting of high-dose ifosfamide followed by a combination of vincristine, doxorubicin and cyclophosphamide, was given with success. Malignant peripheral nerve-sheath tumours are thought to respond weakly to chemotherapy, but the response in our patient was complete.