Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial.The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients).The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper.UMIN000018752.
Retrospective clinical study.The objective of this study is to evaluate the clinical outcome of occipitothoracic fusion for severe destructive cervical lesions in rheumatoid arthritis (RA) patients with myelopathy and/or occipitocervical pain, and to discuss surgical complications. The complication rates are compared between 2 groups treated with different instrumentation techniques.Few studies have reported on the results of occipitothoracic fusion in RA patients.In this study, 56 RA patients with myelopathy and/or occipitocervical pain caused by destructive cervical lesions were studied. The patients were divided into 2 groups A and B, according to the used rod diameter and the application of the cervical pedicle screw system. Group A included 38 patients treated with Unit rods (4.75 mm). Group B included 18 patients treated with cervical pedicle screw system (3.2 mm or 3.5 mm diameter rod). Clinical results and surgical complications were evaluated.Mean follow-up time was 36.2 months. Fifteen patients died during follow-up at the mean age of 67.3 years. None died from their cervical lesions. The neurologic status in 46 patients (82%) had improved at least 1 class in the modified Ranawat scale. Perioperative complications occurred in 16 (28.6%), thoracic spine lesions in 11 (19.6%), implant failure in 13 (23.2%), and surgical site infection in 8 (14.3%). There was a tendency for more fractures and pedicle screw pullouts at the lowest level of the fusion area to occur in group B. The neurologic improvement of patients undergoing occipitothoracic fusion after becoming unable to sit owing to their neurologic deficit was poor.The current study suggests that occipitothoracic fusion for rheumatoid destructive cervical lesions can be effective in improving neurologic deficit if performed while patients can still sit. Improvements to methodology of this surgery can be made.
A prospective comparative study.This study aimed to establish cervical spine morphometry, alignment, and range of motion (ROM) and to clarify the impact of these age-related and degenerative changes.There are no studies that have evaluated differences in the results of cervical spine radiographs between a large series of cervical spondylotic myelopathy (CSM) patients and healthy subjects.We enrolled 1016 consecutive CSM patients who underwent laminoplasty. CSM patients were also divided based on each decade of life between the fourth and ninth decades. We also enrolled a total of 1230 healthy volunteers as asymptomatic subjects in this study. There were at least 100 men and 100 women in each decade of life between the third and eighth decades. Cervical sagittal alignment on neutral and flexion-extension views was measured by the Cobb method at C2-7. ROM was assessed by measuring the difference in alignment between flexion and extension.Cervical lordosis in the neutral position increased gradually with age in both groups. CSM patients showed significantly smaller lordotic angles compared with those shown by asymptomatic subjects within each decade. The total ROM decreased with increasing age in both groups. The total ROM of females was larger than males. The ROM of CSM patients was significantly smaller than asymptomatic subjects. The flexion ROM did not change with aging in either group. There was no significant difference in the flexion ROM between males and females in the two groups. However, the extension ROM decreased gradually in both groups. The extension ROM of CSM patients was significantly smaller than asymptomatic subjects.Age-related and degenerative changes in the cervical spine, alignment, and ROM in each decade of life were established between CSM patients and asymptomatic subjects.
A cross-sectional study.The aim of this study was to investigate the lumbar thecal sac dimensions and spinal cord area on magnetic resonance (MR) imaging in healthy volunteers.There are few reports regarding lumbar spine MRI in healthy subjects, and the difference in spinal canal dimensions by age remains unclear.A total of 629 healthy volunteers were enrolled, including ≥50 males, females, and subjects in each of the 20s to 70s age decades. The anteroposterior and transverse diameters of the thecal sac and axial areas of the thecal sac and spinal cord were measured at the disc levels on T2-weighted axial MR images. The anteroposterior-to-transverse ratio of the thecal sac (APTR) was calculated.The thecal sac area from T12/L1 to L4/5 was reduced in older age group, but there was no significant difference in L5/S1. The thecal sac area was significantly reduced in older age group: 89.9%, 86.0%, 84.6%, 80.3% at T12/L1, L1/2, L2/3, and L3/4, respectively, and 79.9% at L4/5 in subjects in their 70 s relative to that in subjects in their 20 s. The APTR was significantly reduced in older age group from T11/12 to L2/L3 in males and at T10/11, L3/4 and from T11/12 to L2/3 in females. Narrow thecal sac areas <80 mm2 were found in 10 subjects. The spinal cord area was significantly reduced in older age group at T10/11 in males and at T9/10, T10/11, and T11/12 in females. The area was 92.0% at T10/11 in subjects in their 70s relative to the area of subjects in their 20s.The thecal sac area was reduced in older age group from T12/L1 to L4/5, and the thecal sac area was reduced in the anteroposterior and all directions in the upper and lower lumbar area in age group, respectively. Approximately, 3.0% of healthy population in their 50s or older will have severe asymptomatic stenosis.Level of Evidence: 2.
ONO-1714 is a newly developed specific inhibitor for inducible nitric oxide synthase (iNOS). We have shown that ONO-1714 has some neuroprotective effects. In this report, we investigated the effects of ONO-1714 in injured spinal cords, and analyzed the expression of glial cell-line-derived neurotrophic factor (GDNF) after injury. Male Sprague-Dawley rats were subjected to contusive spinal cord injury and administrated 0.1 mg/kg ONO-1714. The injured spinal cords were isolated at appropriate time points and GDNF mRNA was determined by semi-quantitative RT-PCR. GDNF-positive cells were also counted after immunohistochemical stainings. ONO-1714 diminished the early stage production of GDNF after injury as well as it reduced the production of nitric oxide produced by iNOS and apoptotic cells.
In Brief Study Design. A randomized controlled trial. Objective. To investigate the effect of muscle relaxant for muscle blood flow at the trunk muscle in patients with chronic low back pain (LBP). Summary of Background Data. Paraspinal muscle function is widely believed to play a role and considered to be of etiologic significance in LBP, and intramuscular pressure increases and blood flow decreases in the flexion position. Decrease in oxygenated hemoglobin at the trunk muscle is seen in patients with LBP. Methods. A total of 74 male patients with LBP lasting more than 6 months were randomized to 3 treatment groups: (1) physical therapy only (control) (n = 25), (2) administration of eperisone hydrochloride (EMPP) for 4 weeks (n = 24), and (3) McKenzie therapy (n = 25). The primary outcome variables, observed at 2 and 4 weeks, are the Japanese Orthopedic Association LBP score, visual analogue scale (VAS), Faces Pain Scale-Revised, and SF-36. Intramuscular oxygenation was evaluated using near-infrared spectroscopy during lumbar extension and flexion, and oxygenated hemoglobin and deoxygenated hemoglobin were compared. Results. VAS was significantly lower at 4 weeks in the McKenzie group than in the control group. There were no significant changes at 2 weeks in all parameters, however, the relative change of oxygenated hemoglobin during lumbar extension at 4 weeks was significantly higher in the EMPP group when compared with the other 2 groups. The relative change of deoxygenated hemoglobin during lumbar flexion showed a significant difference at 4 weeks in the EMPP group when compared with the control group. Conclusion. Administration of EMPP for 4 weeks improved the LBP in VAS, though not as effective as McKenzie therapy. Our data demonstrated the effects of eperisone hydrochloride on paraspinal muscle hemodynamics improving intramuscular oxygenation during lumbar extension and flexion in patients with chronic LBP. Intramuscular oxygenation at the trunk muscle was evaluated after administration of muscle relaxant. Oxygenated hemoglobin during lumbar extension at 4 weeks was significantly higher after administration of muscle relaxant. The effect of muscle relaxant on paraspinal muscle hemodynamics improving intramuscular oxygenation was demonstrated in patients with chronic low back pain.
A prospective study was conducted on the surgical procedures for lumbar disc herniation.The objective of this study is to investigate the surgical outcomes of different methods when performed by the same surgeon, using a prospective study.Macro discectomy is widely known as a common surgical procedure for lumbar disc herniation, while microdiscectomy in place of Caspar technique (the Caspar method) and microendoscopic discectomy by a posterior approach are reported as less invasive surgical methods for this condition. However, there have not been a significant number of prospective studies conducted to compare different surgical procedures for lumbar disc herniation.The target of our study was a group of 62 patients (male: 43, female: 19) who underwent surgery by macro discectomy (A group) and 57 patients (male: 33, female: 24) who underwent surgery by microdiscectomy in place of Caspar technique (B group). The mean ages at surgery were 34 (14 to 62) years and 41 (18 to 65) years respectively, and the mean duration of follow-up was 2 years and 8 months (12 months to 4 years). For all patients, the surgery was performed by 1 of the authors. The items investigated were the operation time, amount of bleeding, duration of hospitalization, amount of analgesic agent used after surgery, pre- and postoperative scores based on judgment criteria for treatment of lumbar spine disorders established by the Japanese Orthopaedic Association score, visual analog scales (VAS, 0 to 10) for lumbago before surgery and at discharge, VAS for sciatica before surgery and at discharge, perioperative complications, and cases requiring further surgery.There were no significant differences between the 2 surgical procedures in the frequency of use of an analgesic agent after surgery, the pre- and postoperative Japanese Orthopaedic Association scores or postoperative VAS for sciatica. Statistically significant differences were observed in the operation time, amount of bleeding, duration of hospitalization, and postoperative VAS for lumbar pain, but the differences were not large, and may not have been clinically significant.For herniotomy for lumbar disc herniation, both macro discectomy and microdiscectomy are appropriate, as long as surgeons have mastery of the procedures.
Study Design. A prospective imaging study to develop diagnostic criteria. Objective. The aim of this study was to investigate image findings on delayed magnetic resonance imaging (MRI) after the acute phase of spinal cord injury without radiographic abnormality (SCIWORA) and their relationship with symptom severity. Summary of Background Data. MRI is used to diagnose acute neurological injury, with increased signal intensity (ISI) and prevertebral hyperintensity (PVH) often seen in patients with SCIWORA; however, changes after the acute phase are unclear. Methods. We included 68 patients diagnosed with SCIWORA within 48 hours of injury. We then compared their acute (within 2 days) and delayed (after 2 weeks) MRI images. ISI grade (0–3) and ISI and PVH ranges (relative to the C3 vertebral height) were measured. Neurological status at admission and 2 weeks after injury was assessed by the Japanese Orthopaedic Association scoring system for cervical myelopathy (JOA score) and the American Spinal Injury Association impairment scale. Results. For acute MRI, the rates of grade 0, 1, and 2 ISI were 4, 54, and 10 patients, respectively. For delayed MRI, the rates of grade 0, 1, and 2 ISI changed to 3, 31, and 34 patients, respectively. ISI ranges reduced in delayed MRI, but there was no significance. PVH ranges were 3.0 ± 1.7 in acute MRI, and reduced to 1.3 ± 0.9 with significant difference (P < 0.001). There were significant negative correlations with the JOA score for ISI grades on delayed MRI only (r = −0.49). However, there were significant negative correlations with the JOA score for the PVH range on both the acute (r = −0.55) and delayed (r = −0.46) MRI. Conclusion. When comparing acute and delayed MRI, there were significant differences in ISI and PVH findings. Delayed MRI also reflected the clinical symptom severity, giving useful information about the state of the spinal cord. Level of Evidence: 3
