Yuichiro Yoshida

Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice

The present study reports the beneficial effects of an anti-mouse interleukin-6 (IL-6) receptor antibody (MR16-1) on neuropathic pain in mice with spinal cord injury (SCI). Following laminectomy, contusion SCI models were produced using an Infinite Horizon (IH)-impactor. MR16-1 was continuously injected for 14 days using Alzet osmotic pumps. A mouse IL-6 ELISA kit was then used to analyze IL-6 levels in the spinal cord tissue between 12 and 72 h after injury. Motor and sensory functions were evaluated each week using the Basso Mouse Scale (BMS), plantar von Frey and thermal threshold tests. Histological examinations were performed 42 days after SCI. Between 24 and 72 h after SCI, the expression levels of IL-6 were significantly decreased in the MR16-1 treated group. Six weeks after surgery, the BMS score of the MR16-1-treated group indicated significant recovery of neurological functions. MR16-1-treated mice in the SCI group exhibited lower paw withdrawal thresholds in the plantar von Frey and thermal tests, which were used to evaluate allodynia. MR16-1 treatment significantly increased the area of Luxol fast blue-stained tissue, representing spared myelin sheaths. These results indicate that the continuous inhibition of IL-6 signaling by MR16-1 between the early and sub-acute phases following SCI leads to neurological recovery and the suppression of hyperalgesia and allodynia. Overall, our data suggest that the inhibition of severe inflammation may be a promising neuroprotective approach to limit secondary injury following SCI and that an anti-IL-6 receptor antibody may have clinical potential for the treatment of SCI.

Transcranial magnetic stimulation in the diagnosis of cervical compressive myelopathy: comparison with spinal cord evoked potentials.

Study Design. Single-center retrospective study. Objective. To reveal the characteristic changes in central motor conduction time (CMCT) produced by transcranial magnetic stimulation among the responsible levels of cervical compressive myelopathy (CCM). Summary of Background Data. CMCT is a useful and noninvasive measure for evaluating the central motor pathway. However, a systematic correlation between CMCT findings and the responsible level of CCM has so far not been addressed in a large patient cohort. Method. We measured CMCT in 75 patients with CCM who were determined by intraoperative spinal cord evoked potentials to have a single site of conduction abnormality at the intervertebral level. Twenty-one healthy controls were also evaluated. Motor evoked potentials, compound muscle action potentials, and F wave were recorded from bilateral abductor digiti minimi (ADM) and abductor hallucis (AH) muscles. CMCT was calculated as follows: motor evoked potentials latency − (CMAPs latency + F latency − 1)/2 (ms). Result. The mean values of ADM-CMCT and AH-CMCT at each responsible level were significantly longer than those of normal values (P < 0.01). However, the mean value of ADM-CMCT at the C6–C7 level was markedly shorter than those at the other levels, whereas the mean values of AH-CMCT were not significantly different between each responsible level. We determined that an ADM-CMCT longer than 7.9 ms (mean + 2.5 standard deviation) was abnormal. Using this definition, the sensitivity of ADM-CMCT for CCM was 92% for C3–C4 myelopathy, 95% for C4–C5, 58% for C5–C6, and 9% for C6–C7. Conclusion. ADM-CMCT is useful for the screening of CCM rostral to the C5–C6 level. Diagnosis of patients with C6–C7 myelopathy should include assessment of the AH-CMCT. Level of Evidence: 4

Usefulness of an early MRI-based classification system for predicting vertebral collapse and pseudoarthrosis after osteoporotic vertebral fractures.

Study Design: Retrospective review. Objective: To clarify whether an early magnetic resonance imaging–based classification predicts pseudoarthrosis and final vertebral collapse in osteoporotic vertebral fractures. Summary of Background: Initial therapy for osteoporotic vertebral fractures involves bed rest, orthotic use, and plaster casts. However, in some cases, pain persists because of progressive vertebral collapse or pseudoarthrosis. Prediction of these complications immediately after fractures can facilitate early proactive treatment despite the early prognosis being generally poor. Methods: A total of 109 patients (129 fractured vertebrae, 88 females, 21 males, and average age 79 y) followed up over 6 months after conservative treatment for thoracolumbar vertebral fractures were included. Early midsagittal T1-weighted and T2-weighted magnetic resonance images were analyzed. The incidence of final vertebral body collapse, pseudoarthrosis conversion, and delayed spinal cord paralysis were examined retrospectively for each vertebral fracture type. Results: According to the T1-weighted image-based classification, 74 of the vertebrae (57%) had total-type fractures. The final vertebral body collapse rate was significantly higher in this type than in others. Pseudoarthrosis was observed in 20 total-type fractures in 20 patients (18.3%); pseudoarthrosis conversion rate was significantly higher in these patients than in others. Delayed spinal cord paralysis occurred in only 1 patient (0.9%) with total-type fracture. According to the T2-weighted image-based classification, 69 vertebrae had the hyperintense wide-type fractures, which was the most common fracture type (53%). Hypointense wide-type fractures were associated with a significantly higher incidence of final vertebral body collapse, pseudoarthrosis, and delayed spinal cord paralysis. When total-type fractures of the T1-weighted image-based classification were subclassified according to the T2-weighted image-based classification, a significantly higher pseudoarthrosis conversion rate was observed in hypointense wide-type fractures. Conclusions: Our results suggest that the radiologic prognosis can be estimated to a limited extent by determining the degree and extent of osteoporotic vertebral fractures using an early magnetic resonance imaging–based classification.

Biomechanical analysis of cervical myelopathy due to ossification of the posterior longitudinal ligament: Effects of posterior decompression and kyphosis following decompression

Cervical ossification of the posterior longitudinal ligament (OPLL) results in myelopathy. Conservative treatment is usually ineffective, thus, surgical treatment is required. One of the reasons for the poor surgical outcome following laminoplasty for cervical OPLL is kyphosis. In the present study, a 3-dimensional finite element method (3D-FEM) was used to analyze the stress distribution in preoperative, posterior decompression and kyphosis models of OPLL. The 3D-FEM spinal cord model established in this study consisted of gray and white matter, as well as pia mater. For the preoperative model, 30% anterior static compression was applied to OPLL. For the posterior decompression model, the lamina was shifted backwards and for the kyphosis model, the spinal cord was studied at 10, 20, 30, 40 and 50° kyphosis. In the preoperative model, high stress distributions were observed in the spinal cord. In the posterior decompression model, stresses were lower than those observed in the preoperative model. In the kyphosis model, an increase in the angle of kyphosis resulted in augmented stress on the spinal cord. Therefore, the results of the present study indicated that posterior decompression was effective, but stress distribution increased with the progression of kyphosis. In cases where kyphosis progresses following surgery, detailed follow-ups are required in case the symptoms worsen.

Percutaneous radiofrequency facet joint denervation with monitoring of compound muscle action potential of the multifidus muscle group for treating chronic low back pain: a preliminary report.

Study Design: A retrospective review. Objective: The aim of this study was to study the effectiveness of percutaneous radiofrequency neurotomy of facet joints by monitoring compound muscle action potentials (CMAPs) of the multifidus muscle group as an objective index of treatment efficacy. Summary of Background: Percutaneous radiofrequency neurotomy of the medial branches of the dorsal rami of the lumbar nerves is a widely accepted treatment for chronic lumbar intervertebral joint pain. However, its success rate has varied in different studies because an objective method for evaluating the facet joint denervation is lacking. Methods: Fifty-five patients (age range, 19–76 y; mean age, 55 y) with low back pain persisting for ≥3 months, in whom facet block and/or block of the medial branch of the dorsal ramus were only temporarily effective, were included. The Japanese Orthopaedic Association (JOA) scoring system for back pain was used for clinical assessment. JOA scores were measured before treatment and 1 week, 3 months, 6 months, and 12 months afterward. The improvement rate was calculated with ≥40% improvement rate defined as successful, and the success rate was subsequently evaluated. Results: The patient success rate was 75% (41/55) at 1 week, 71% (39/55) at 3 months, 60% (33/55) at 6 months, and 51% (28/55) at 12 months after treatment. Two cases had minor postoperative complications, which were localized burning pain lasting <1 week at the site of electrode insertion. Conclusions: Our results suggest that percutaneous radiofrequency facet joint denervation with CMAPs monitoring is a safe, long-lasting, and effective treatment for chronic facet joint pain. CMAP monitoring may be useful as an objective index for facet denervation.

Cervical ossification of the posterior longitudinal ligament: Biomechanical analysis of the influence of static and dynamic factors

Abstract Objective Cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) is induced by static factors, dynamic factors, or a combination of both. We used a three-dimensional finite element method (3D-FEM) to analyze the stress distributions in the cervical spinal cord under static compression, dynamic compression, or a combination of both in the context of OPLL. Methods Experimental conditions were established for the 3D-FEM spinal cord, lamina, and hill-shaped OPLL. To simulate static compression of the spinal cord, anterior compression at 10, 20, and 30% of the anterior–posterior diameter of the spinal cord was applied by the OPLL. To simulate dynamic compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction. To simulate combined static and dynamic compression under 10 and 20% anterior static compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction. Results The stress distribution in the spinal cord increased following static and dynamic compression by cervical OPLL. However, the stress distribution did not increase throughout the entire spinal cord. For combined static and dynamic compression, the stress distribution increased as the static compression increased, even for a mild range of motion (ROM). Conclusion Symptoms may appear under static or dynamic compression only. However, under static compression, the stress distribution increases with the ROM of the responsible level and this makes it very likely that symptoms will worsen. We conclude that cervical OPLL myelopathy is induced by static factors, dynamic factors, and a combination of both.

Selective laminoplasty after the preoperative diagnosis of the responsible level using spinal cord evoked potentials in elderly patients with cervical spondylotic myelopathy: a preliminary report.

Study Design A preliminary report of a new operative method termed selective laminoplasty after the preoperative diagnosis of the responsible level using spinal cord evoked potentials (SCEPs) in elderly patients with cervical spondylotic myelopathy. Objective To introduce the method and clinical results for selective laminoplasty. Summary of Background Data Clinical results for conventional laminoplasty and anterior decompression and fusion guided by SCEPs have been reported. However, there have been no reports that consider SCEP results for selecting the optimal level in lamioplasty for cervical spondylotic myelopathy. Methods Seven elderly patients who underwent selective laminoplasty were followed for a minimum of 12 months. The T2-high–intensity area on magnetic resonance imaging, the responsible level detected by SCEPs, and the laminoplasty level were recorded. The operative time, intraoperative bleeding, clinical results including the Japanese Orthopaedic Association score, recovery rate, Nurick grading scale, and visual analog scale of axial pain were investigated preoperatively and postoperatively. Results The responsible intervertebral levels were at C3-C4 in 3 patients and at C4-C5 in 4 patients. These were identical for SCEP recorded after median nerve stimulation and transcranial electric stimulation. High-intensity area on T2-weighted magnetic resonance imaging was seen in 6 patients (3 at C3-C4 and 3 at C4-C5). The average operative time was 106 minutes and the average amount of bleeding was 20 mL. Neurologic recovery was achieved in all patients except 1 who had severe myelopathy. Visual analog scales of axial pain were 41.3±33.9 before surgery and 18.0±19.4 at final follow-up. The Japanese Orthopaedic Association score and the Nurick grade improved in 6 patients but did not change in 1 patient. Conclusions Preliminary clinical results for selective laminoplasty were satisfactory in all but 1 case. Although long-term results are not yet available, we consider this method to be less invasive and capable of giving satisfactory clinical results and benefits for elderly patients.

Prolonged Survival of Experimental Extremity Allografts: A New Protocol with Total Body Irradiation, Granulocyte-Colony Stimulation Factor, and FK506

The induction of a high‐level of chimerism (macrochimerism) may be the most reliable strategy for achieving donor‐specific tolerance. The purpose of this study was to evaluate the efficacy of a new protocol using total‐body irradiation (TBI) and granulocyte‐colony stimulation factor (G‐CSF) to induce high‐level chimerism following rat whole‐limb allotransplantation. In this study, we investigated whether the timing of TBI influenced the period of graft survival. In total, 50 whole‐limb allotransplants from LacZ transgenic rats to LEW rats were performed. TBI was performed at days 0 and 14, and G‐CSF was given for 4 days after TBI. FK506 was given for 28 days after transplant. Nontreated limb allografts were rejected after 4.2 days. The survival time was prolonged to 64 days in the FK506 monotherapy group. In the group receiving TBI at day 14, limb allograft survival was significantly prolonged to 81 days. In the group receiving TBI at day 0, 26% of recipients died but in the surviving recipients the grafts survived for longer than 1 year without lethal graft‐versus‐host disease (GVHD). Polymerase chain reaction (PCR) analysis revealed a high level of intrabone marrow chimerism in the recipient, thus demonstrating successful induction of macrochimerism. A new protocol of pretransplant TBI followed by treatment with G‐CSF and FK506 was found to induce a high level of chimerism and to significantly prolong the survival of limb allografts in recipients without lethal GVHD.

Effects of differences in age and body height on normal values of central motor conduction time determined by F-waves

Objectives: To investigate the effect on central motor conduction time (CMCT) based on the relationship between age and height in normal subjects. Design: Retrospective study. Methods: One hundred and ninety nine normal subjects (107 men and 92 women; mean age 39.0 ± 16.4 years; mean height 164.5 ± 8.8 cm) participated in the study. The approximate ages of subjects were as follows: 82 (20–29 years old), 32 (30–39 years old), 32 (40–49 years old), 28 (50–59 years old), and 25 (≧60 years old). The heights of 9, 49, 79, 53, and 9 subjects were <150 cm, 150–160 cm, 160–170 cm, 170–180 cm, and >180 cm, respectively. CMCT- abductor digiti minimi (ADM) and abductor hallucis (AH) were calculated by subtracting the peripheral motor conduction time (PMCT) from the onset latency of motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation. PMCT was calculated from the latencies of the compound muscle action potentials (CMAPs) and F-waves as follows: (latency of CMAPs + latency of F-waves -1)/2. Outcome measures: CMCT-ADM and CMCT-AH. Results: The normative values were 5.2 ± 0.8 ms and 11.8 ± 1.3 ms for CMCT-ADM and CMCT-AH, respectively. CMCT-ADM was not significantly correlated with age (P = 0.196) and body height (P = 0.158). CMCT-AH had significantly positive, linear correlations with age and body height (CMCT-AH = 0.014 × age + 10.971, P = 0.011, R = 0.179 and CMCT-AH = 0.026 × body height + 7.158, P = 0.010, R = 0.182). Conclusions: We suggest normative values of 3.2–7.2 ms in CMCT-ADM for subjects exerting slight effort on ADM regardless age and body height. CMCT-AH had significantly positive, linear correlations with age and body height.

Diagnosis and Characters of Non-Specific Low Back Pain in Japan: The Yamaguchi Low Back Pain Study.

Study Design Cross sectional data from the Yamaguchi low back pain study conducted in Yamaguchi prefecture, Japan, was used for this analysis. Methods A total of 320 patients were recruited from walk-in orthopedic clinics in Yamaguchi Prefecture, Japan. Patients visited the clinics primarily for low back pain (LBP) and sought treatment between April and May 2015. A self-questionnaire was completed by patients, while radiographic testing and neurological and physical examination was performed by the orthopedist in each hospital. The cause and characters of LBP was determined following examination of the data, regional anesthesia and block injection. Results ‘Specific LBP’ was diagnosed in 250 (78%) patients and non-diagnosable, ‘non-specific LBP’ in 70 (22%) patients. The VAS scores of patients were: LBP, 5.8±0.18; leg pain, 2.9±0.18 and the intensity of leg numbness was 1.9±0.16. Item scores for SF-8 were: general health, 46.6±0.40; physical function, 43.5±0.51; physical limitations, 42.8±0.53; body pain, 42.1±0.52; vitality, 48.4±0.37; social function, 46.9±0.53; emotional problems, 48.9±0.43; mental health, 46.9±0.43. Conclusions The incidence of non-specific LBP in Japan was lower than previous reports from western countries, presumably because of variation in the diagnosis of LBP between different health care systems. In Japan, 78% of cases were classified as ‘specific LBP’ by orthopedists. Identification of the definitive cause of LBP should help to improve the quality of LBP treatment.