Takeo Furuya

A new concept for making decisions regarding the surgical approach for cervical ossification of the posterior longitudinal ligament: the K-line.

Study Design. To report a new index, the K-line, for deciding the surgical approach for cervical ossification of the posterior longitudinal ligament (OPLL). Objective. To analyze the correlation between the K–line-based classification of cervical OPLL patients and their surgical outcome. Summary of Background Data. Previous studies showed that kyphotic alignment of the cervical spine and a large OPLL are major factors causing poor surgical outcome after laminoplasty for cervical OPLL patients. However, no report has evaluated these 2 factors in 1 parameter. Methods. The K-line was defined as a line that connects the midpoints of the spinal canal at C2 and C7. Twenty-seven patients who had cervical OPLL and underwent posterior decompression surgery were classified into 2 groups according to their K-line classification. OPLL did not exceed the K-line in the K-line (+) group and did exceed it in the K-line (−) group. By intraoperative ultrasonography, we evaluated the posterior shift of the spinal cord after the posterior decompression procedure. The Japanese Orthopedic Association scores before surgery and 1 year after surgery were evaluated, and the recovery rate was calculated. Results. Eight patients were classified as K-line (−), and 19 patients were classified as K-line (+). The mean recovery rate was 13.9% in the K-line (−) group and 66.0% in the K-line (+) group (P < 0.01). Ultrasonography showed that the posterior shift of the spinal cord was insufficient in the K-line (−) group. Conclusion. The present results demonstrate that a sufficient posterior shift of the spinal cord and neurologic improvement will not be obtained after posterior decompression surgery in the K-line (−) group. Our new index, the K-line, is a simple and practical tool for making decisions regarding the surgical approach for cervical OPLL patients.

Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: a prospective randomized study.

Study Design. Prospective randomized trial. Objective. To examine the effect of the tumor necrosis factor alpha (TNF-&agr;) inhibitor, etanercept, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis. Summary of Background Data. TNF-&agr; is thought to play a crucial role in the radicular pain caused by lumbar disc herniation and spinal stenosis. Intravenous infusion of infliximab for sciatica has been examined in 2 studies; however, the results were equivocal. Methods. Eighty patients with low back and radicular leg pain were investigated. We diagnosed the patients by physical examination, and X-ray and magnetic resonance imaging. In 40 patients, we epidurally administered 2.0 mL of lidocaine and 10 mg of etanercept onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone was used in 40 patients. Low back pain, leg pain, and leg numbness were evaluated using a visual analogue scale (VAS) and Oswestry Disability Index (ODI) score before and for 1 month after epidural administration. Results. Low back pain, leg pain, and leg numbness in the 2 groups were not significantly different before epidural administration. Epidural administration of etanercept was more effective than dexamethasone for leg pain (3 days, and 1, 2, and 4 weeks: P < 0.05), low back pain (3 days, and 1 and 2 weeks: P < 0.05), and leg numbness (3 days, and 1 and 2 weeks: P < 0.05). No adverse event was observed in either group. Conclusion. Our results indicate that epidural administration of a TNF-&agr; inhibitor onto the spinal nerve produced pain relief, but no adverse event. TNF-&agr; inhibitors may be useful tools for the treatment of radicular pain caused by spinal stenosis.

Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

Purpose Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA. Materials and Methods Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearmans correlation coefficient by rank test. Results Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant. Conclusion PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.

Anomalous vertebral arteries in the extra- and intraosseous regions of the craniovertebral junction visualized by 3-dimensional computed tomographic angiography: analysis of 100 consecutive surgical cases and review of the literature.

Study Design. Consecutive case series and literature review. Objective. To describe the utility of 3-dimensional computed tomographic angiography (3D CTA) for evaluating vertebral artery (VA) anomalies before surgery. Summary of Background Data. Recent advances in instrumentation surgery at the craniovertebral junction (CVJ) enable us to perform rigid internal fixation. However, the risk of VA injury as a complication of the surgery has become a major problem. Thus, the importance of preoperative evaluation of the VA course has been emphasized. Methods. Cases of 100 consecutive patients who underwent CVJ instrumentation surgery since July 1998 were analyzed. Occipitocervical/thoracic or C1–C2 posterior fusion was performed for atlantoaxial subluxation (AAS) in 59 patients and cervical fixation including C2 was required for middle-to-lower cervical lesions in 41 patients. Twenty-seven patients with AAS had a congenital skeletal anomaly (CSA) at the CVJ including os odontoideum and occipitalization of C1 (AAS-CSA[+] group). Anomalous VAs at the extra- and intraosseous regions were evaluated by 3D CTA. Results. No neurovascular injury occurred during surgery. Abnormal courses of the VA at the extraosseous region were detected in 10 cases: 2 had fenestration and 8 had a persistent first intersegmental artery. All 10 cases were in the AAS-CSA(+) group. A high-riding VA was detected in 31 cases. Fourteen out of the 31 cases were in the AAS-CSA(+) group, indicating 51.9% of the AAS-CSA(+) group had high-riding VA. In the AAS-CSA(+) group, a C1–C2 transarticular screw and C2 pedicle screw were actually inserted in 58% and 31% of the planned insertions, respectively. Conclusion. The present findings suggest that the frequency of an abnormal VA at the extra- and intraosseous regions is increased when patients have AAS and CSA at the CVJ. Using preoperative 3D CTA, we can precisely identify anomalous VAs and thereby reduce the risk of their intraoperative injury.

Efficacy and reliability of highly functional open source DICOM software (OsiriX) in spine surgery

We evaluated the feasibility and reliability of open source Digital Imaging and COmmunication in Medicine (DICOM) imaging software, OsiriX (Antoine Rosset, 2003-2009), in spine surgery. CT data were used and processed with OsiriX and with commercial software for comparison. Images were reconstructed and compared in volume rendering (VR) and multi-planar reconstruction (MPR) mode. When all images were compared, the three-dimensional (3D) reconstructed images from both software packages showed considerable consistency in VR mode. Measurements in MPR mode also showed similar values with no statistically significant difference. These results demonstrate that OsiriX has approximately equivalent values to commercial software and provides reliable preoperative 3D information for the surgical field. In addition, any clinician, can obtain information using OsiriX at any time. Thus, OsiriX is a helpful tool in preoperative planning for spine surgery.

Neuroprotective effects of granulocyte colony-stimulating factor and relationship to promotion of angiogenesis after spinal cord injury in rats: laboratory investigation.

OBJECT Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects on the CNS. The authors have previously demonstrated that G-CSF also exerts neuroprotective effects in experimental spinal cord injury (SCI) by enhancing migration of bone marrow-derived cells into the damaged spinal cord, increasing glial differentiation of bone marrow-derived cells, enhancing antiapoptotic effects on both neurons and oligodendrocytes, and by reducing demyelination and expression of inflammatory cytokines. Because the degree of angiogenesis in the subacute phase after SCI correlates with regenerative responses, it is possible that G-CSFs neuroprotective effects after SCI are due to enhancement of angiogenesis. The aim of this study was to assess the effects of G-CSF on the vascular system after SCI. METHODS A contusive SCI rat model was used and the animals were randomly allocated to either a G-CSF-treated group or a control group. Integrity of the blood-spinal cord barrier was evaluated by measuring the degree of edema in the cord and the volume of extravasation. For histological evaluation, cryosections were immunostained with anti-von Willebrand factor and the number of vessels was counted to assess revascularization. Real-time reverse transcriptase polymerase chain reaction was performed to assess expression of angiogenic cytokines, and recovery of motor function was assessed with function tests. RESULTS In the G-CSF-treated rats, the total number of vessels with a diameter > 20 μm was significantly larger and expression of angiogenic cytokines was significantly higher than those in the control group. The G-CSF-treated group showed significantly greater recovery of hindlimb function than the control group. CONCLUSIONS These results suggest that G-CSF exerts neuroprotective effects via promotion of angiogenesis after SCI.

Static versus dynamic factors for the development of myelopathy in patients with cervical ossification of the posterior longitudinal ligament

We studied 27 patients with cervical ossification of the posterior longitudinal ligament (OPLL) but no clinical symptoms of myelopathy. We investigated the occupation ratio of the spinal canal by OPLL with cervical radiographs, assessed the morphological types of OPLL, and measured the segmental range of motion (ROM) at the level of maximum cord compression on flexion and extension radiographs. Patients were classified as having continuous-type OPLL (17 patients), mixed-type OPLL (seven patients), or segmental-type OPLL (three patients). The segmental ROM was negatively correlated with the OPLL occupation ratio (r=-0.49, p<0.01). No patient developed myelopathy during the study period. Three patients with massive OPLL did not develop myelopathy and the mobility of their cervical spine was highly restricted, suggesting that dynamic factors such as the segmental ROM preferentially contribute to the development of myelopathy in patients with cervical OPLL. Thus, by controlling the dynamic factors (hypermobility), we might be able to reduce neurological deterioration in patients with cervical OPLL.

Granulocyte Colony-Stimulating Factor (G-CSF) Protects Oligpdendrocyte and Promotes Hindlimb Functional Recovery after Spinal Cord Injury in Rats

Background Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI). The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats. Methods Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne). Recombinant human G-CSF (15.0 µg/kg) was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points. Results Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF- alpha) in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs. Conclusions G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.

Treatment of rat spinal cord injury with a Rho-kinase inhibitor and bone marrow stromal cell transplantation.

In light of reports that the administration of fasudil, a Rho-kinase inhibitor, improved rats locomotor abilities following spinal cord injury, we hypothesized that combining fasudil with another type of therapy, such as stem cell transplantation, might further improve the level of locomotor recovery. Bone marrow stromal cells (BMSCs) are readily available for stem cell therapy. In the present study, we examined whether fasudil combined with BMSC transplantation would produce synergistic effects on recovery. Adult female Sprague-Dawley rats were subjected to spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 Kdyn). Immediately after contusion, they were administrated fasudil intrathecally for 4 weeks. GFP rat-derived BMSCs (2.5x10(6)) were injected into the lesion site 14 days after contusion. Locomotor recovery was assessed for 9 weeks with BBB scoring. Sensory tests were conducted at 8 weeks. Biotinylated dextran amine (BDA) was injected into the sensory-motor cortex at 9 weeks. In addition to an untreated control group, the study also included a fasudil-only group and a BMSC-only group in order to compare the effects of combined therapy vs. single-agent therapy. Animals were perfused transcardially 11 weeks after contusion, and histological examinations were performed. The combined therapy group showed statistically better locomotor recovery than the untreated control group at 8 and 9 weeks after contusion. Neither of the two single-agent treatments improved open field locomotor function. Sensory tests showed no statistically significant difference by treatment. Histological and immunohistochemical studies provided some supporting evidence for better locomotor recovery following combined therapy. The average area of the cystic cavity was significantly smaller in the fasudil+BMSC group than in the control group. The number of 5-HT nerve fibers was significantly higher in the fasudil+BMSC group than in the control group on the rostral side of the lesion site. BDA-labeled fibers on the caudal side of the lesion epicenter were observed only in the fasudil+BMSC group. On the other hand, only small numbers of GFP-labeled grafted cells remained 9 weeks after transplantation, and these were mainly localized at the site of injection. Double immunofluorescence studies showed no evidence of differentiation of grafted BMSCs into glial cells or neurons. The Rho-kinase inhibitor fasudil combined with BMSC transplantation resulted in better locomotor recovery than occurred in the untreated control group. However, the data failed to demonstrate significant synergism from combined therapy compared with the levels of recovery following single-agent treatment.

Uni- and bilateral instrumented posterolateral fusion of the lumbar spine with local bone grafting: a prospective study with a 2-year follow-up.

Study Design. Prospective trial. Objective. To examine the bone union and clinical results after unilateral or bilateral instrumented posterolateral fusion surgery using a local bone graft. Summary of Background Data. The iliac crest bone graft technique for lumbar posterolateral fusion surgery is widely used; however, donor site problems such as pain and sensory disturbance have been reported. Local bone has been used for bilateral multisegment fusion surgery; however, outcomes have been poor because of insufficient amounts of local bone used. This study evaluated unilateral and bilateral posterolateral fusion at 3 levels using a local bone graft. Methods. Sixty-two patients diagnosed with degenerated spondylolisthesis at 3 levels were divided into 2 groups. All underwent decompression and bilateral instrumented posterolateral fusion. However, a unilateral local bone graft was used in 32 patients and bilateral local bone graft was used in 30 patients. The amount of bone grafting, proportion of patients with bone union, duration of bone union, visual analog scale score, Japanese Orthopedic Association score, and Oswestry Disability Index were evaluated before and 2 years after surgery. Results. Visual analog scale score, Japanese Orthopedic Association score, and Oswestry Disability Index were not significantly different between the 2 groups before and after surgery (P > 0.05). The amount of local bone graft used for each segment was significantly less in the bilateral group (P < 0.05). The proportion of patients with rates of bone union and instability were 86% and 9%, respectively, in the unilateral group, but significantly poorer at 60% and 34% in the bilateral group. Conclusion. If multisegment fusion (3-level fusion) is performed, bilateral local bone grafting results in a poor rate of bone union because of an insufficiency of local bone. Unilateral bone grafting is recommended because better rates of bone union and stability are achieved.