A novel osseointegrated percutaneous prosthetic system for the treatment of patients with transfemoral amputation: A prospective study of 51 patients.

Patients with transfemoral amputation (TFA) often experience problems related to the use of socket-suspended prostheses. The clinical development of osseointegrated percutaneous prostheses for patients with a TFA started in 1990, based on the long-term successful results of osseointegrated dental implants. Between 1999 and 2007, 51 patients with 55 TFAs were consecutively enrolled in a prospective, single-centre non-randomised study and followed for two years. The indication for amputation was trauma in 33 patients (65%) and tumour in 12 (24%). A two-stage surgical procedure was used to introduce a percutaneous implant to which an external amputation prosthesis was attached. The assessment of outcome included the use of two self-report questionnaires, the Questionnaire for Persons with a Transfemoral Amputation (Q-TFA) and the Short-Form (SF)-36. The cumulative survival at two years' follow-up was 92%. The Q-TFA showed improved prosthetic use, mobility, global situation and fewer problems (all p < 0.001). The physical function SF-36 scores were also improved (p < 0.001). Superficial infection was the most frequent complication, occurring 41 times in 28 patients (rate of infection 54.9%). Most were treated effectively with oral antibiotics. The implant was removed in four patients because of loosening (three aseptic, one infection). Osseointegrated percutaneous implants constitute a novel form of treatment for patients with TFA. The high cumulative survival rate at two years (92%) combined with enhanced prosthetic use and mobility, fewer problems and improved quality of life, supports the 'revolutionary change' that patients with TFA have reported following treatment with osseointegrated percutaneous prostheses.

Evoked thalamic neuronal activity following DRG application of two nucleus pulposus derived cell populations: an experimental study in rats.

PURPOSE: To investigate the effects on evoked thalamic neuronal activity of application of notochordal cells and chondrocyte-like cells derived from nucleus pulposus (NP) onto a dorsal root ganglion (DRG) and to compare these effects with a previously reported increased thalamic activity induced by NP. METHODS: Nucleus pulposus was harvested from tail discs of adult rats and the disc cells were separated into two cell populations, notochordal cells and chondrocyte-like cells. The two cell populations were applied separately, or in combination, to the L4 DRG of anaesthetised female Sprague-Dawley rats during acute electrophysiological experiments. In control experiments, cell suspension medium was applied on the DRG. Recordings from the contralateral thalamus were sampled for 40 min while electrically stimulating the ipsilateral sciatic nerve at above Aδ-fibre thresholds. RESULTS: Application of notochordal cells resulted in a decrease in evoked thalamic activity within 10 min while chondrocyte-like cells did not induce any changes during the 40 min of recording. The difference in evoked thalamic activity 40 min after notochordal and chondrocyte-like cell application, respectively, was statistically significant. Neither an increased concentration of chondrocyte-like cells alone nor a combination of the two cell populations induced any changes in thalamic activity. CONCLUSIONS: Separate exposure of the DRG to the two NP-derived cell populations induced different effects on evoked thalamic activity, but none of the tested cell samples induced an increase in neuronal activity similar to that previously observed with NP. This indicates a high complexity of the interaction between NP and nervous tissue.

Nucleus pulposus-induced nerve root injury: effects of diclofenac and ketoprofen.

MAIN PROBLEM: Nucleus pulposus and/or chronic compression can induce spinal nerve root injury. Inflammation has been proposed as having major importance in the pathophysiologic mechanisms involved in the induction of such injuries. Corticosteroids, potent anti-inflammatory drugs, have been demonstrated to reduce nucleus pulposus-induced spinal nerve root injury. The aim of the present study was to assess the effects of two potent non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac and ketoprofen, in experimental nucleus pulposus-induced spinal nerve root injury in a pig model. METHODS: Eighteen pigs were included in the study. Autologous nucleus pulposus was harvested from a lumbar disc and applied locally around the first sacral nerve root after a partial laminectomy of the first and second sacral vertebrae. Six pigs were treated with daily intramuscular injections of diclofenac, 3 mg/kg body weight, for 7 days. Six other pigs were treated with daily intramuscular injections of ketoprofen, 4 mg/kg body weight, for 7 days. As controls, six pigs received injections with physiologic saline. After 7 days, the pigs were reanesthetized and the nerve conduction velocity over the exposed nerve root area was determined. RESULTS: The nerve conduction velocity was significantly higher in pigs treated with diclofenac than in the saline-treated controls, (57 +/- 6 m/s vs 38 +/- 18 m/s, P<0.05, Student's t-test). The velocity in pigs treated with ketoprofen, 42 +/- 24 m/s, did not differ significantly from that of controls. CONCLUSIONS: This study of two potent NSAIDs indicates that nucleus pulposus-induced nerve root dysfunction may be reduced by diclofenac but not by ketoprofen. The reason for this difference is not known, but it might be related to the fact that ketoprofen and diclofenac belong to different NSAID subgroups and have a different selectivity for the two cyclo-oxygenases COX-1 and COX-2.

Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica.

Proinflammatory cytokines have been identified in herniated intervertebral discs in humans, and such cytokines have experimentally been demonstrated to be important in the pathophysiological mechanisms of disc herniation. Cerebrospinal fluid (CSF) and serum concentrations of interleukin (IL)-1beta IL-6, IL-8, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were investigated using the enzyme-linked immunosorbent assay (ELISA) technique in 39 patients with lumbar disc herniation and sciatica. Pain duration and pain intensity (visual analogue scale, VAS) were recorded at inclusion, and a clinical examination was performed evaluating neurological findings. The extent of disc herniation (protrusion or extrusion/sequestration) was evaluated perioperatively. Normal concentrations of IL-1beta, IL-6, IFN-gamma and TNF-alpha were present in CSF and serum in almost all patients with lumbar disc herniation. The concentrations of IL-8 in CSF were increased in 12 out of 39 patients, and these increased levels of IL-8 correlated to a short duration of pain and to more pronounced herniation (extrusion or sequestration). No relationship between IL-8 concentrations in CSF and pain intensity, positive neurological findings or a positive straight leg-raising (SLR) test was found. The observation of increased concentrations of IL-8 in CSF in patients with a short duration of symptoms supports the concept of the initial involvement of inflammatory mechanisms after a disc herniation. The finding that most of the patients with increased concentrations of IL-8 in CSF had an extrusion or a sequestration may suggest that the increase in IL-8 is related to mechanical nerve root compression, but may also indicate a biochemical effect exerted by the herniated disc on the surrounding tissue. Further studies on the potential role of IL-8 as a biomarker for disc herniation are warranted.

Effects of diclofenac and ketoprofen on nerve conduction velocity in experimental nerve root compression.

STUDY DESIGN: The effects of diclofenac and ketoprofen on nerve conduction velocity in experimental nerve root compression were evaluated in a setup using an established pig model. OBJECTIVE: To assess the effects of two potent nonsteroidal antiinflammatory drugs, diclofenac and ketoprofen, in experimental nerve root compression. SUMMARY OF BACKGROUND DATA: Compression of spinal nerve roots is recognized to be of major etiologic importance for several common spinal pain syndromes. Secondary inflammatory changes, induced by microvascular permeability changes and leakage of inflammatory mediators into the endoneural tissue, have been proposed as important for the induction of spinal nerve root injury by chronic compression. METHODS: This study involved 21 pigs. An ameroid constrictor was used to induce compression. Seven pigs were treated with daily intramuscular injections of diclofenac 3 mg/kg for 7 days. Seven other pigs were treated with daily intramuscular injections of ketoprofen 4 mg/kg. For a control, seven pigs did not receive any drug treatment. After 7 days, the pigs were reanesthetized, and the nerve conduction velocity in the compressed nerve root segments was determined. RESULTS: The nerve conduction velocity was significantly higher (P < 0.05, Student's t test) in the pigs treated with diclofenac (50 +/- 16 m/second) than in the untreated pigs (32 +/- 15 m/second). The nerve conduction velocity also was significantly higher (P < 0.05) in the pigs treated with ketoprofen (59 +/- 16 m/second) than in the untreated pigs. There were no significant differences in nerve conduction velocity between pigs treated with ketoprofen and those treated with diclofenac. CONCLUSIONS: The findings indicate that intramuscular administration of diclofenac or ketoprofen, both potent antiinflammatory drugs, may reduce nerve root dysfunction induced by compression of spinal nerve roots in an experimental pig model.

Effects of anulus fibrosus and experimentally degenerated nucleus pulposus on nerve root conduction velocity: relevance of previous experimental investigations using normal nucleus pulposus.

STUDY DESIGN: Nerve conduction velocity was measured in the pig cauda equina after local application of anulus fibrosus or in vitro/postmortem degenerated nucleus pulposus from the same pig. OBJECTIVES: To analyze the effects of anulus fibrosus and degenerated nucleus pulposus on nerve conduction velocity. SUMMARY OF BACKGROUND DATA: Previous studies on nucleus pulposus-induced effects on nerve roots have used normal, nondegenerated nucleus pulposus. Because both anulus fibrosus and degenerated nucleus pulposus are commonly seen in the clinical situation of disc herniation, the value of the previous work could be questioned. METHODS: Anulus fibrosus and nucleus pulposus were harvested using a retroperitoneal approach. The nucleus pulposus was degenerated artificially either by addition of sodium lactate with HCl added to form a pH of either 6.0 or 3.5 (in vitro degeneration), or by storing the nucleus pulposus at 4 C until a pH of 6.0 (postmortem degeneration) was reached. After epidural application, the nerve conduction velocity was determined at 7 days (anulus fibrosus) or 3 days (degenerated nucleus pulposus). RESULTS: Application of anulus fibrosus did not induce any reduction of nerve conduction velocity. In vitro and postmortem degenerated nucleus pulposus induced a reduction of nerve conduction velocity similar to that of normal nucleus pulposus. CONCLUSIONS: Although only nerve function and not pain was assessed, it seems likely that previous experiments using normal nucleus pulposus may be relevant for evaluating the pathophysiologic mechanisms behind the nucleus pulposus-induced nerve root injury, also in a clinical perspective.

Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity: possible implications for future pharmacologic treatment strategies of sciatica.

STUDY DESIGN: The possibility to prevent nucleus pulposus-induced functional and structural nerve root injury by selective tumor necrosis factor-alpha inhibition was assessed in an experimental model in the pig spine. OBJECTIVE: The objective of the study was to evaluate the role of tumor necrosis factor-alpha in the mediation of nucleus pulposus-induced nerve injury by using selective inhibition. SUMMARY OF BACKGROUND DATA: The cytokine tumor necrosis factor-alpha has been suggested to play a key role in the nerve root injury induced by local application of nucleus pulposus. However, previous studies have not been able to distinguish the effects between tumor necrosis factor-alpha and other disc-related cytokines because of the use of nonspecific cytokine inhibition. METHODS: Autologous nucleus pulposus was harvested from a lumbar disc and applied to the porcine sacrococcygeal cauda equina. The pigs were simultaneously treated with two selective tumor necrosis factor-alpha inhibitors (etanercept n = 8 and infliximab n = 5), a heparin analogue (enoxaparin n = 5) or saline for control (n = 5). After 7 days the nerve conduction velocity over the application zone was determined and samples of the exposed nerve roots were collected for light microscopic evaluation. RESULTS: The two tumor necrosis factor-alpha inhibitors prevented the reduction of nerve conduction velocity and also seemed to limit the nerve fiber injury, the intracapillary thrombus formation, and the intraneural edema formation. However, treatment with enoxaparin did not seem to be different from control regarding reduction of nerve conduction velocity or histologic changes. CONCLUSIONS: The data clearly indicate that tumor necrosis factor-alpha is involved in the basic pathophysiologic events leading to nerve root structural and functional changes after local application of nucleus pulposus. The study therefore provides a basic scientific platform with potential clinical implications regarding the use of anti-tumor necrosis factor-alpha medication as treatment in patients with disc herniation and sciatica.

Nitric oxide as a mediator of nucleus pulposus-induced effects on spinal nerve roots.

Nerve root dysfunction and sciatic pain in disc herniation are considered to be caused by mechanical compression and related to the presence of nucleus pulposus in the epidural space. Autologous nucleus pulposus has been shown to induce endoneural edema and to decrease nerve-conduction velocity in spinal nerve roots in experimental disc herniation models, and inflammatory mediators have been suggested to be involved in these mechanisms. Nitric oxide, a potent inflammatory mediator, is implicated in vasoregulation, neurotransmission, and neuropathic pain. Nitric oxide synthesis can be induced by different cytokines, e.g., tumor necrosis factor-alpha, which recently was shown to be of pathophysiological importance in experimental disc herniation. The enzyme nitric oxide synthase mediates the production of nitric oxide. Three series of experiments were performed in rat and pig disc herniation models to (a) investigate nitric oxide synthase activity in spinal nerve roots after exposure to autologous nucleus pulposus and (b) evaluate the effects of systemic treatment with aminoguanidine, a nitric oxide synthase inhibitor, on vascular permeability and nerve-conduction velocity. In a disc herniation model in the rat, calcium-independent nitric oxide synthase activity was measured in nerve roots exposed to nucleus pulposus; however, no nitric oxide synthase activity was detected in nerve roots from animals that underwent a sham operation, reflecting increased inducible nitric oxide synthase activity. In nucleus pulposus-exposed spinal nerve roots in the pig, the edema was less severe after systemic aminoguanidine administration than without aminoguanidine treatment. Aminoguanidine treatment also significantly reduced the negative effect of nucleus pulposus on nerve-conduction velocity in spinal nerve roots in the pig. These results demonstrate that nucleus pulposus increases inducible nitric oxide synthase activity in spinal nerve roots and that nitric oxide synthase inhibition reduces nucleus pulposus-induced edema and prevents reduction of nerve-conduction velocity. Furthermore, the results suggest that nitric oxide is involved in the pathophysiological effects of nucleus pulposus in disc herniation.

Evaluation of the psychophysical detection threshold level for vibrotactile and pressure stimulation of prosthetic limbs using bone anchorage or soft tissue support.

In the present study the psychophysical detection threshold levels mechanical stimulation of 32 prosthetic limbs were determined. Prosthetic limbs were anchored to the bone by means of an implant (n=17) or supported by a socket enclosing the amputation stump (n=15). Detection threshold levels were assessed for pressure and vibratory stimulation of the prosthesis and the limb at the contralateral side (control). Following vibratory stimulation, thresholds were increased on an average 20% for socket prostheses. but approached those of the control for bone-anchored prostheses. For pressure stimulation, thresholds were increased up to 60% for socket prostheses and 40% for bone-anchored prostheses compared to the control. While bone-anchored prostheses yielded significantly lower threshold levels than socket prostheses, there was no significant difference between both treatments regarding pressure stimulation. Results were applicable to both upper and lower limb amputees. It could be concluded that detection thresholds for pressure and especially vibratory stimulation of prosthetic limbs were generally higher than for control limbs. The outcome was related to the prosthetic limb design with bone-anchored prostheses yielding better perception than socket prostheses.

Nucleus pulposus inhibits the axonal outgrowth of cultured dorsal root ganglion cells.

Although it is well established that nucleus pulposus cells may induce structural and functional changes in adjacent nerve roots when placed epidurally, it is not known whether this is due to direct neurotoxic effects or whether the nerve roots are affected indirectly by reduction of nutrition and inflammatory/immunologic mechanisms. In the present study we assessed the effects of various tissues on cultured dorsal root ganglions from newborn rats. Nucleus pulposus was found to have a toxic effect on the axons by blocking axonal outgrowth, but no similar effects on the nerve cell bodies (extra-ganglionic nerve cell density, nerve cell arborisation) were found as compared to the series with only culture medium. Sterile water for 1 or 24 h (positive controls) induced significant effects by all four criteria, whereas medium without nerve growth factor, fat and frozen nucleus pulposus had no statistically significant effects. The study thus showed that there are direct axonotoxic effects induced by the nucleus pulposus, and since frozen nucleus pulposus did not have any effects, it may be assumed that the mechanisms are related to substances produced by the nucleus pulposus cells. The presented model allows for future studies on the neurotoxic properties of nucleus pulposus cell-derived candidate substances.

A long-term (4- to 12-year) follow-up study of surgical treatment of lumbar spinal stenosis.

Limited data are available about the long-term outcome of surgical treatment for lumbar spinal stenosis, and there is a wide variation in reported success rates. There is also a controversy regarding differences in long-term outcome between patients undergoing decompressive surgery alone and those undergoing both decompression and fusion. The aim of this study was to evaluate the long-term clinical outcome and possible complications of decompressive surgery, with special reference to possible differences between patients undergoing fusion, with or without instrumentation, and those undergoing decompression alone. All 124 patients undergoing first-time surgery for lumbar spinal stenosis between 1982 and 1991 at our department were included, and their medical records were reviewed retrospectively. Ninety-six of the patients were available for follow-up and were re-examined by an independent investigator and assessed with a questionnaire after a mean follow-up period of 7.1 (range 4.0-12.2) years. Sixty-five percent of all the patients at the follow-up were subjectively satisfied. Eighty-eight percent of the patients reported constant or daily leg pain preoperatively compared to 43% at follow-up. Constant or daily low back pain was reported by 83% of the patients preoperatively compared to 45% at follow-up. Improvement in walking capacity was found in most patients, and only 4% of the patients who had a preoperatively documented maximum walking distance reported a decreased walking capacity. Twenty-four (25%) of all patients used analgesics daily at the time of follow-up, 34 patients (35%) occasionally and 38 patients (40%) never. The patients with fusions, instrumented or non-instrumented, did not differ significantly from the unfused patients regarding any of the above-mentioned parameters. The results of the study showed that most patients demonstrated a considerable improvement in walking capacity at follow-up. This improvement was significant (P < 0.001) and of clinical importance. A significant improvement regarding both low back pain and leg pain was found postoperatively compared to preoperatively (P < 0.001). There were no statistical differences, judged by all the evaluated parameters, regarding the clinical outcome between patients who were fused and those who were not. Neither were any significant differences found between instrumented fusions compared to uninstrumented fusions. In accordance with most other long-term follow-up studies, about two-thirds (65%) of the patients claimed a satisfactory result at follow-up.

Methylprednisolone reduces the early vascular permeability increase in spinal nerve roots induced by epidural nucleus pulposus application.

Autologous nucleus pulposus is known to have injurious effects on spinal nerve roots when applied epidurally. Both inflammatory and immunological mechanisms have been implicated in this regard. Various proinflammatory substances might be released or activated by nucleus pulposus and might affect the endoneural nerve root vessels. The present study assessed nucleus pulposus-induced early vascular reactions and the possibility of blocking these reactions with intravenous, high-dose, methylprednisolone pretreatment. In 25 pigs, the S2 and S3 nerve roots were exposed. In five pigs (control group), retroperitoneal fat was applied epidurally on the nerve roots, and the other 20 pigs had nucleus pulposus applied. This group was sub-divided into the treatment group (n = 8), in which the pigs were pretreated with intravenous high-dose methylprednisolone (30 mg/kg body weight), and the nontreatment group (n = 12), in which the pigs received a corresponding volume of saline solution. After 2 hours, Evans blue labeled albumin was injected intravenously 5 minutes before death. Endoneural extravasation of Evans blue labeled albumin was evaluated with fluorescence microscopy. A marked albumin leakage was found in 67% of the nontreated animals, in 25% of those in the treatment group, and in none of the control animals. These results demonstrate that nucleus pulposus can induce a rapid increase in endoneural vascular permeability in spinal nerve roots after epidural application. This increase can be partially prevented by pretreatment with high-dose methylprednisolone.

Transport of epidurally applied horseradish peroxidase to the endoneurial space of dorsal root ganglia: a light and electron microscopic study.

The route by which an epidurally applied macromolecule might reach the endoneurial space of spinal nerve roots was assessed with light and electron microscopy in a pig model established to explore the pathophysiology of disk herniation. Horseradish peroxidase (HRP) dissolved in saline was infused epidurally. Animals were sacrificed after 5 minutes (n = 5) or 30 minutes (n = 5). Two control animals received only a saline infusion and were sacrificed after 30 minutes. Nerve root specimens were collected, fixed, and exposed to the HRP substrate, 3.3'-di-amino-benzidine (DAB). The distribution of HRP reaction product in the nerve tissue was studied with light and electron microscopy. In 5-minute specimens, HRP was found in epidural and intradural vessel walls. At the nerve root level, HRP was detected in meningeal membranes but was not seen in periaxonal space. In addition to engaging the outer cell layers of the dorsal root ganglion (DRG) capsule, HRP was detected as a gradient among the peripherally located nerve cell bodies and sometimes among the emerging afferent axons. The 30-minute group demonstrated similar findings. The results confirm that HRP can reach the periaxonal spaces of lumbar DRG within 5 minutes after epidural application. Although the transport mechanism is not fully understood, the DRG may constitute an anatomical location allowing epidurally applied macromolecules entrance to the endoneurial space, either by direct diffusion or via vascular transport. The demonstrated transport route may have implications in the pathophysiology of sciatica in conjunction with lumbar disc herniation.

Protein markers in cerebrospinal fluid in experimental nerve root injury. A study of slow-onset chronic compression effects or the biochemical effects of nucleus pulposus on sacral nerve roots.

STUDY DESIGN: Measurement of changes in cerebrospinal fluid concentrations of nerve tissue markers, total proteins, and immunoglobulin after compression of nerve root or application of nucleus pulposus in a pig model. OBJECTIVES: To assess whether compression or application of nucleus pulposus to spinal nerve roots may cause increased levels of cerebrospinal fluid markers of nerve tissue damage and total proteins, and whether synthesis of immunoglobulins may be induced in cerebrospinal fluid. SUMMARY OF BACKGROUND DATA: Previous studies have reported that there seems to be a relationship between elevated cerebrospinal fluid total protein concentrations, nerve tissue markers, clinical findings, and compression of the nerve root evaluated by radiologic changes in patients with sciatica. METHODS: Subjects included 41 pigs, including 5 control animals. In two groups of experimental animals (n = 7; n = 5), an ameroid constrictor was slid onto the S1 nerve root. In two other groups (n = 7; n = 5), nucleus pulposus harvested from the L2-L3 disc was applied to the S1 nerve root. Two sham animal groups (n = 7; n = 5) underwent the same laminectomy. Twenty-one pigs underwent reoperation after 1 week, and 15 pigs after 4 weeks. A syringe was used to remove 3 mL of cerebrospinal fluid at L4-L5. Concentrations of total proteins, the light subunit of the neurofilament protein, S-100 protein, neuron-specific enolase, and glial fibrillary acidic protein were measured, and the presence of oligoclonal bands (immunoglobulins) were assayed in cerebrospinal fluid. RESULTS: The pigs with compressed S1 nerve root had considerably higher neurofilament protein and total protein concentrations in their cerebrospinal fluid than the-control animals (P < 0.001 and P < 0.01, respectively) or the sham animals (P < 0.001 and P < 0.05) in the 1-week experiment. Nucleus pulposus did not induce a significant increase in concentrations of the different protein markers. The presence of oligoclonal bands in cerebrospinal fluid in the experimental groups did not differ between the control and sham animals. CONCLUSIONS: The neurofilament protein and total protein concentrations in cerebrospinal fluid may have diagnostic importance in cases wherein clinical findings are not clearly related to the radiologic changes and vice versa. These protein markers also may be useful tools in different experimental models.

Markers of nerve tissue injury in the cerebrospinal fluid in patients with lumbar disc herniation and sciatica.

STUDY DESIGN: The light subunit of neurofilament protein, S-100 protein, neuron-specific enolase, and glial fibrillary acidic protein were determined in the cerebrospinal fluid in patients with lumbar disc herniation and in control patients. OBJECTIVES: To determine whether nerve root injury caused by disc herniation increases the levels of nerve and glial cell injury markers in the cerebrospinal fluid. SUMMARY OF BACKGROUND DATA: Markers of nerve tissue injury can be analyzed in the cerebrospinal fluid, allowing characterization of the cell types involved and the degree of disease in patients with neurologic disorders. METHODS: Cerebrospinal fluid samples were obtained by preoperative lumbar puncture in patients who underwent surgery for lumbar disc herniation and in patients who underwent lower extremity surgery (control group), neurofilament protein (light subunit) and glial fibrillary acidic protein were analyzed by enzyme-linked immunosorbent assay and S-100 protein and neuron-specific enolase by radioimmunoassay and luminescence immunoassay, respectively. In the disc herniation group the concentrations of the four markers were evaluated regarding possible correlation to patient history, computed tomographic findings, and clinical findings. RESULTS: Cerebrospinal fluid concentration of neurofilament protein (light subunit) and S-100 were increased in the disc herniation group compared with that in control subjects (1158 +/- 383 ng/L vs. 152 +/- 14 ng/L, P < 0.01; 1963 +/- 231 ng/L vs. 1003 +/- 152 ng/L, P < 0.05, respectively). No statistical differences in neuron-specific enolase and glial fibrillary acidic protein concentrations were observed between the groups. Disc herniation patients with fewer than 3 months' duration of subjective symptoms had higher neurofilament protein levels than did patients with longer duration. None of the markers was related to preoperative clinical or computed tomographic findings. Patients with persistent neurologic findings at follow-up 2-3 months after surgery had higher levels of neurofilament protein before surgery compared with-those without sequelae. CONCLUSIONS: Patients with disc herniation and sciatica have increased concentrations of neurofilament protein and S-100 in the cerebrospinal fluid, which indicates damage of axons and Schwann cells in the affected nerve root.

Effects of lidocaine on nucleus pulposus-induced nerve root injury. A neurophysiologic and histologic study of the pig cauda equina.

STUDY DESIGN: Application of autologous nucleus pulposus on nerve roots and treatment with local application of lidocaine in the pig. OBJECTIVES: Studies of the effects of lidocaine on nucleus pulposus-exposed nerve roots. SUMMARY OF BACKGROUND DATA: Nerve root infiltration may improve radicular symptoms beyond the pharmacologic duration of local anesthetics, but the mechanisms for this effect are not known. METHODS: Nucleus pulposus was harvested from a lumbar disc and placed onto the sacrococcygeal cauda equina in pigs. In Series 1, early lidocaine treatment of nucleus pulposus-induced nerve root injury, pigs received 2% lidocaine (n = 5) or saline (n = 5) before and after surgery. Nerve conduction velocity and histologic appearance were studied after 3 days. In Series 2, delayed lidocaine treatment of nucleus pulposus-induced nerve root injury, after 7 days 2% lidocaine was administered epidurally to nucleus pulposus-exposed (n = 4) and -nonexposed (n = 4) nerve roots. Nerve conduction velocity, muscle action potentials, and histologic appearance were assessed. RESULTS: In Series 1, early treatment with lidocaine limited the reduction in nerve conduction velocity. The epidural inflammation was less in lidocaine treated animals. In Series 2, nerve conduction velocity was lower in nucleus pulposus-exposed animals than in nonexposed animals. The initial reduction of nerve conduction velocity and muscle action potential was similar between the groups, but the recovery of muscle action potential was slower and less complete in nucleus pulposus-exposed nerve roots. There was minimal histologic nerve injury in both series and in both protocols. CONCLUSIONS: Early treatment with lidocaine may reduce nucleus pulposus-induced nerve root injury. Lidocaine induced a delayed recovery in nerve roots exposed to nucleus pulposus. Further studies are needed to clarify the therapeutic effects of nerve root infiltration and the pathophysiology of nucleus pulposus-induced nerve root injury.