Takayuki Fujiyoshi

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.

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.

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.

Cervical myelopathy in patients with ossification of the posterior longitudinal ligament

OBJECT The authors assessed the clinical course in patients with a narrowed cervical spinal canal caused by ossification of the posterior longitudinal ligament (OPLL), but who have no or only mild myelopathy. Additionally, the authors analyzed the factors contributing to the development and aggravation of myelopathy in patients with OPLLinduced spinal canal stenosis. METHODS Between 1997 and 2004, the authors selected treatments for patients with cervical OPLL in whom the residual space available for the spinal cord was < or = 12 mm. Treatment decisions were based on the severity of myelopathy at presentation. Twenty-one patients with no or mild myelopathy (defined as a Japanese Orthopaedic Association [JOA] scale score > or = 14 points) received conservative treatment, with a mean follow-up period of 4.5 years. In 20 patients with moderate or severe myelopathy (JOA scale score < 14 points), the authors performed surgery via an anterior approach. The clinical course in these patients was assessed with the JOA scale and the OPLL types were classified. The authors evaluated the range of motion between C-1 and C-7, the developmental segmental sagittal diameter, the percentage of spinal canal diameter occupied by the OPLL (% ratio), and the residual space available for the spinal cord on cervical radiographs; T2-weighted MR images were examined for high signal changes (HSCs). RESULTS In the conservative treatment group, 8 patients showed improvement, 12 remained unchanged, and 1 patients condition became slightly worse during the observation period. Fifteen patients in this group had mixedtype, 3 had continuous-type, 2 had localized-type, and 1 had a segmental-type OPLL. In the surgically treated group, there were 12 patients with segmental-type, 10 patients with mixed-type, and 1 with localized-type OPLL. The mean range of motion at C1-7 was 36.4 degrees in the conservatively treated group and 46.5 degrees in the surgical group (p < 0.05). No significant difference was seen between the groups in terms of developmental segmental sagittal diameter, % ratio, or residual space available for the cord. No HSCs were noted in the conservative group, while 17 patients in the surgical group had HSCs (p < 0.05). CONCLUSIONS In the present study, the authors demonstrate that the mobility of the cervical spine and the type of OPLL are important factors contributing to the development and aggravation of myelopathy in patients with OPLLinduced spinal canal stenosis. The authors advocate conservative treatment in most patients with OPLLs who have no or only mild myelopathy, even in the presence of spinal canal narrowing.

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.

Multicenter Prospective Nonrandomized Controlled Clinical Trial to Prove Neurotherapeutic Effects of Granulocyte Colony-stimulating Factor for Acute Spinal Cord Injury: Analyses of Follow-up Cases After at Least 1 Year

Study Design. An open-labeled multicenter prospective nonrandomized controlled clinical trial. Objective. To confirm the feasibility of using granulocyte colony-stimulating factor (G-CSF) for treatment of acute spinal cord injury (SCI). Summary of Background Data. We previously reported that G-CSF promotes functional recovery after compression-induced SCI in mice. On the basis of these findings, we conducted a multicenter prospective controlled clinical trial to assess the feasibility of G-CSF therapy for patients with acute SCI. Methods. The trial ran from August 2009 to March 2011, and included 41 patients with SCI treated within 48 hours of onset. Informed consent was obtained from all patients. After providing consent, patients were divided into 2 groups. In the G-CSF group (17 patients), G-CSF (10 &mgr;g/kg/d) was intravenously administered for 5 consecutive days, and in the control group (24 patients), patients were similarly treated except for the G-CSF administration. We evaluated motor and sensory functions using the American Spinal Cord Injury Association score and American Spinal Cord Injury Association impairment scale at 1 week, 3 months, 6 months, and 1 year after onset. Results. Only 2 patients did not experience American Spinal Cord Injury Association impairment scale improvement in the G-CSF group. In contrast, 15 patients in the control group did not experience American Spinal Cord Injury Association impairment scale improvement. In the analysis of increased American Spinal Cord Injury Association motor score, a significant increase in G-CSF group was detected from 1 week after the administration compared with the control group. After that, some spontaneous increase of motor score was detected in control group, but the significant increase in G-CSF group was maintained until 1 year of follow-up. Conclusion. Despite the limitation that patient selection was not randomized, the present results suggest the possibility that G-CSF administration has beneficial effects on neurological recovery in patients with acute SCI. Level of Evidence: 3

Short-segment fixation without fusion for thoracolumbar burst fractures with neurological deficit can preserve thoracolumbar motion without resulting in post-traumatic disc degeneration: a 10-year follow-up study.

Study Design. Prospective consecutive series. Objective. To evaluate the post-traumatic disc degeneration and range of motion 10 years after short-segment fixation without fusion for thoracolumbar burst fractures with neurological deficit. Summary of Background Data. Early clinical results of short-segment fixation without fusion for thoracolumbar burst fractures were satisfactory. However, the long-term results have not been reported, and post-traumatic disc degeneration and preservation of thoracolumbar motion have not been elucidated. Methods. Twelve patients who had thoracolumbar burst fractures and associated incomplete neurological deficit, operatively treated within 4 days of admission and had their implants removed within 1 year, were prospectively followed for at least 10 years. Following indirect reduction and pedicle screw fixation, transpedicular intracorporeal hydroxyapatite grafting to the fractured vertebrae was performed. Results. Sagittal alignment was improved from a mean preoperative kyphosis of 17° to −2° (lordosis) by operation, but was found to have slightly deteriorated to 2° at the final follow-up observation. With respect to back pain, 8 patients did not report back pain. Three reported occasional minimal pain, and 1 reported moderate pain. None reported severe pain or needed daily dosages of analgesics. Regarding disc degeneration, the shape of the disc adjacent to the fractured vertebra had not changed from the preoperative to the 10-year postoperative magnetic resonance image (MRI). Although signal intensity of the disc had decreased by 1 grade from the preoperative to the 2-year postoperative MRI, the intensity had not changed from the 2-year postoperative MRI to the 10-year postoperative MRI. At the 10-year follow-up, flexion-extension radiographs revealed that a mean range of motion at the disc adjacent to the fractured vertebra was 12º (range; 5–19). Conclusion. This unprecedented 10-year follow-up study demonstrated that posterior indirect reduction, transpedicular hydroxyapatite grafting, and pedicle screw fixation does not require fusion to a segment, thereby preserves thoracolumbar motion without resulting in post-traumatic disc degeneration. Level of Evidence: 4

Perioperative Complications in 155 Patients Who Underwent Oblique Lateral Interbody Fusion Surgery: Perspectives and Indications From a Retrospective, Multicenter Survey.

Study Design. A retrospective multicenter survey. Objective. To investigate the perioperative complications of oblique lateral interbody fusion (OLIF) surgery. Summary of Background Data. OLIF has been widely performed to achieve minimally invasive, rigid lumbar lateral interbody fusion. The associated perioperative complications are not yet well described. Methods. The participants were patients who underwent OLIF surgery under the diagnosis of degenerative lumbar diseases between April 2013 and May 2015 at 11 affiliated medical institutions. The collected data were classified into intraoperative and early-stage postoperative (⩽1 mo) complications. The intraoperative complications were then subcategorized into organ damage (neural, vertebral, vascular, and others) and other complications, mainly related to instrumental failure. The collected data were also divided and analyzed based on whether the surgeon was certified to perform the surgery and the incidence of complications in the early (April 2013–March 2014) and late stages (April 2014–May 2015) of OLIF introduction. Results. In the 155 included patients, 75 complications were reported (incidence rate, 48.3%). The most common complication was endplate fracture/subsidence (18.7%), followed by transient psoas weakness and thigh numbness (13.5%) and segmental artery injury (2.6%). Almost all these complications were transient, except for three patients who had permanent damage: one had ureteral injury and two had neurological injury. Postoperative complications included surgical site infection (1.9%) and reoperation (1.9%). Whether the primary operator was experienced did not affect the incidence of complications. Regarding the introductory stage, the incidence of complications was 50% in the early stage and 38% in the late stage. Conclusion. The overall incidence of perioperative complications of OLIF surgery reached 48.3%, of which only 1.9% resulted in permanent damage. Our analysis based on surgeon experience indicated that the OLIF procedure could be performed without increasing incidence of complications, under the guidance of experienced supervisors. Level of Evidence: 3

Interferon-γ Decreases Chondroitin Sulfate Proteoglycan Expression and Enhances Hindlimb Function after Spinal Cord Injury in Mice

Glial cells, including astrocytes and macrophages/microglia, are thought to modulate pathological states following spinal cord injury (SCI). In the present study, we evaluated the therapeutic effects of interferon-γ (IFN-γ), which is one of the cytokines regulating glial function, in a mouse contusive SCI model. We found that intraperitoneal injection of IFN-γ significantly facilitated locomotor improvement following SCI. Immunohistochemistry demonstrated that IFN-γ decreased the accumulation of chondroitin sulfate proteoglycans (CSPGs), which are critical axon outgrowth inhibitors produced by reactive astrocytes in the injured central nervous system (CNS). Quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting demonstrated that neurocan, one of several CSPGs, was reduced in the spinal cords of IFN-γ-treated mice compared to vehicle-treated mice. Consistently, IFN-γ inhibited the production of neurocan from activated astrocytes in vitro. In addition, IFN-γ treatment enhanced the number of serotonin-positive nerve fibers and myelinated nerve fibers around the lesion epicenter. We also found that glial cell line-derived neurotrophic factor (GDNF) and insulin-like growth factor-1 (IGF-1) were upregulated post-SCI following IFN-γ treatment. Our results indicate that IFN-γ exhibits therapeutic effects in mouse contusive SCI, presumably by reducing CSPG expression from reactive astrocytes and increasing the expression of neurotrophic factors.

Neuroprotective Therapy Using Granulocyte Colony-Stimulating Factor for Patients With Worsening Symptoms of Thoracic Myelopathy A Multicenter Prospective Controlled Trial

Study Design. An open-labeled multicenter prospective controlled clinical trial. Objective. To confirm the feasibility of granulocyte colony–stimulating factor (G-CSF) administration for patients with thoracic myelopathy. Summary of Background Data. Although G-CSF is best known as an important cytokine commonly used to treat neutropenia, it also has nonhematopoietic functions. Previous experimental studies have shown that G-CSF can enhance tissue regeneration of several organs, such as the heart and the brain. We previously reported that G-CSF promotes functional recovery after spinal cord injury in rodents. On the basis of those findings, we started a clinical trial of neuroprotective therapy, using G-CSF for patients with worsening symptoms of thoracic myelopathy. Methods. Patients whose Japanese Orthopaedic Association (JOA) score for thoracic myelopathy had decreased 2 points or more during a recent 1-month period were eligible for entry. After giving informed consent, patients were assigned to G-CSF and control groups. The G-CSF group (n = 10) received G-CSF 10 &mgr;g/kg per day intravenously for 5 consecutive days. The control group (n = 14) received similar treatments as the G-CSF group except for G-CSF administration. The primary outcome was JOA recovery rate at 1 month after G-CSF administration or initial treatment. Results. There was greater improvement in neurological functioning between baseline and 1-month follow-up in the G-CSF group (JOA recovery rate: 29.1 ± 20.5%) than in the control group (JOA recovery rate: 1.1 ± 4.2%) (P < 0.01). No serious adverse events occurred during or after the G-CSF administration. Conclusion. The results provide evidence that G-CSF administration caused neurological recovery in patients with worsening symptoms of thoracic compression myelopathy.