Masahiro Funaba

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

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 of Severe Carpal Tunnel Syndrome Using Nerve Conduction Study and Ultrasonography

This study investigated the correlation between nerve conduction study and ultrasonographic findings for assessment of the usefulness of ultrasonography in determining carpal tunnel syndrome severity. Hands of adults with carpal tunnel syndrome were assessed using ultrasound and nerve conduction studies and grouped according to median nerve cross-sectional area (CSA). There were significant differences (p < 0.01) in mean median nerve CSA between controls, patients with median sensory nerve conduction velocity ≤40 m/s and patients with absent sensory nerve action potential and between controls, patients with median nerve distal motor latency ≥4.5 ms and patients with absent compound muscle action potentials of the abductor pollicis brevis. This is the first report to define median nerve CSA cutoff values (18 mm(2)) for determining carpal tunnel syndrome severity in patients with absent compound muscle action potentials of the abductor pollicis brevis. Median nerve CSA values below the cutoff values should prompt clinicians to consider other disorders, such as cervical compressive myelopathy.

Finite element analysis of compression fractures at the thoracolumbar junction using models constructed from medical images

Vertebral fractures commonly occur at the thoracolumbar junction. These fractures can be treated with mild residual deformity in many cases, but are reportedly associated with increased risk of secondary vertebral fractures. In the present study, a three-dimensional (3D) whole spine model was constructed using the finite element method to explore the mechanism of development of compression fractures. The 3D model of the whole spine, from the cervical spine to the pelvis, was constructed from computed tomography (CT) images of an adult male. Using a normal spine model and spine models with compression fractures at the T11, T12 or L1 vertebrae, the distribution of strain was analyzed in the vertebrae after load application. The normal spine model demonstrated greater strain around the thoracolumbar junction and the middle thoracic spine, while the compression fracture models indicated focused strain at the fracture site and adjacent vertebrae. Increased load time resulted in the extension of the strain region up to the middle thoracic spine. The present findings, that secondary vertebral fractures commonly occur around the fracture site, and may also affect the thoracic vertebrae, are consistent with previous clinical and experimental results. These results suggest that follow-up examinations of compression fractures at the thoracolumbar junction should include the thoracic spine and adjacent vertebrae. The current data also demonstrate that models created from CT images can be used for various analyses.

Use of Central Motor Conduction Time and Spinal Cord Evoked Potentials in the Electrophysiological Assessment of Compressive Cervical Myelopathy

Study Design. A retrospective study. Objective. This study investigated the pathophysiology of compressive cervical myelopathy (CCM) with prolonged central motor conduction time (CMCT) in the upper limbs (ULs) rather than lower limbs (LLs) and prolonged CMCT at the thoracic level (TL). Summary of Background Data. Earlier reports indicated the usefulness of CMCT to assess preoperative CCM severity. However, little information exists on patients with prolonged CMCT-UL rather than CMCT-LL and prolonged CMCT-TL. Methods. Ninety-four patients (61 men, 33 women; age 28–87 years) with CCM who underwent cervical laminoplasty participated. Fifty-three volunteers provided normal data on CMCT-UL and LL. CMCT-TL was calculated as CMCT-LL – CMCT-UL. We defined three groups: group U, prolonged CMCT-UL rather than CMCT-LL (n = 14); group E, prolonged CMCT-UL and CMCT-LL equality (n = 43); and group L, prolonged CMCT-TL (n = 37). We evaluated intraoperative recording of spinal cord evoked potentials (SCEPs), neurological findings, and surgical outcomes. Results. Control mean CMCT-UL was 5.2 ± 0.7 ms, CMCT-LL was 11.8 ± 1.1 ms, and CMCT-TL was 6.6 ± 1.2 ms. SCEPs results were significantly different between CCM patients in group U and L (P < 0.01). Almost all patients in three groups showed hyperreflexia of the patellar tendon reflex, but great toe position sense was abnormal in most patients in group L only. Japanese Orthopedics Association (JOA) scores improved postoperatively in all patients. There was a significant difference in recovery rate of the JOA score between group L and other groups (both P < 0.05). Conclusion. Multimodal SCEPs, clinical findings, and surgical outcomes showed that patients with CCM and prolonged CMCT-TL had substantial disorders of the gray matter, lateral corticospinal tract, and posterior funiculus. Spine surgeons should be aware that prognosis may be poor even after surgery in patients with severe myelopathy such as prolonged CMCT-TL. Level of Evidence: 4

Utility of the central motor conduction time recorded from the abductor pollicis brevis and the abductor digiti minimi muscles in patients with C6–7 myelopathy

Objective: Central motor conduction time (CMCT) recorded from the abductor pollicis brevis (CMCT-APB) and abductor digiti minimi (CMCT-ADM) muscles may enable the evaluation of patients with C6–7 myelopathy. CMCT is more useful for the evaluation of the function of spinal cord than magnetic resonance imaging (MRI) findings. CMCT may be associated with age and height. However, there are few reports regarding CMCT-APB in normal subjects. This study aimed to investigate the relationships between age, height, and conduction parameters in normal subjects to assess the effectiveness of using CMCT-APB and CMCT-ADM for the evaluation of patients with C6–7 and C7–T1 myelopathy. Design: Retrospective study. Methods: Fifteen patients with cervical compressive myelopathy at C6–7 (11 patients) or C7-T1 (4 patients) level were enrolled. The control group consisted of 150 normal subjects (mean age 45.8±17.0 years; mean height 163.6±8.9 cm). Motor evoked potentials induced by transcranial magnetic stimulation and F-waves were used to determine CMCT. Outcome measures: CMCT-APB, CMCT-ADM. Results: The normative values of CMCT-APB and CMCT-ADM were 5.3±0.7 ms and 5.2±0.8 ms, respectively. CMCT-APB was significantly longer than CMCT-ADM for patients with C6–7 myelopathy (P < 0.05). Neither of the CMCTs for those with C7–T1 myelopathy were significantly different from those of controls, but CMCT-APB was more prolonged than CMCT-ADM in patients with C6–C7 myelopathy. Conclusions: CMCTs improve the accuracy of the diagnosis of myelopathy by pinpointing the lesion in combination with MRI imaging. Selective CMCT-APB prolongation may be seen in patients with C6–7 myelopathy but not C7-T1 myelopathy.

Age‑related changes of the spinal cord: A biomechanical study

Although it is known that aging plays an important role in the incidence and progression of cervical spondylotic myelopathy (CSM), the underlying mechanism is unclear. Studies that used fresh bovine cervical spinal cord report the gray matter of the cervical spinal cord as being more rigid and fragile than the white matter. However, there are no reports regarding the association between aging an tensile and Finite Element Method (FEM). Therefore, FEM was used based on the data pertaining to the mechanical features of older bovine cervical spinal cord to explain the pathogenesis of CSM in elderly patients. Tensile tests were conducted for white and gray matter separately in young and old bovine cervical spinal cords, and compared with their respective mechanical features. Based on the data obtained, FEM analysis was further performed, which included static and dynamic factors to describe the internal stress distribution changes of the spinal cord. These results demonstrated that the mechanical strength of young bovine spinal cords is different from that of old bovine spinal cords. The gray matter of the older spinal cord was significantly softer and more resistant to rupture compared with that of younger spinal cords (P<0.05). Among the old, although the gray matter was more fragile than the white matter, it was similar to the white matter in terms of its rigidity (P<0.05). The in vitro data were subjected to three compression patterns. The FEM analysis demonstrated that the stress level rises higher in the old spinal cords in response to similar compression, when compared with young spinal cords. These results demonstrate that in analyzing the response of the spinal cord to compression, the age of patients is an important factor to be considered, in addition to the degree of compression, compression speed and parts of the spinal cord compression factor.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

Introduction 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. Methods and analysis 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). Ethics and dissemination 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. Trial registration number UMIN000018752.

Operative methods for delayed paralysis after osteoporotic vertebral fracture

Purpose: How to select operative methods for delayed paralysis after osteoporotic vertebral fracture remains a matter of debate. It is unclear which procedure provides better neurological and functional recovery. This study aimed to compare the various operative methods and investigate postoperative outcomes. Methods: The study included 42 delayed paralysis patients (mean age 73.7 years). The operative methods were posterior spinal shortening osteotomy with direct decompression and short or long fusion and posterior laminectomy and short fusion with vertebroplasty. All patients in the vertebroplasty group were fitted with hooks to prevent correction loss. We investigated postoperative complications, surgery time, intraoperative blood loss, and changes in walking ability and local kyphotic angle (LKA). Patients were divided into three groups: shortening with a peripheral fusion range of one intervertebral level (the SS group, n = 18), the same procedure with a peripheral fusion range of ≥2 intervertebral levels (the SL group, n = 12), and posterior laminectomy and short fusion with vertebroplasty (the VP group, n = 12). Results: Postoperative complications were observed in five patients, all of whom were in the SS and SL group. There were no significant differences between the SS and SL groups. The VP group experienced significantly shorter mean surgery times, significantly lower mean intraoperative blood loss, and an improvement in paralysis, walking ability, LKA, and correction loss. Overall, the VP group had significantly better outcomes. Conclusion: Posterior laminectomy and short fusion with vertebroplasty with the addition of hooks is useful in cases of delayed paralysis in elderly patients.

Cauda Equina Conduction Time Determined by F-Waves in Normal Subjects and Patients With Neurogenic Intermittent Claudication Caused by Lumbar Spinal Stenosis

Purpose: Lumbar spinal stenosis typically presents with neurogenic intermittent claudication. The aim of this study was to investigate cauda equina conduction time (CECT) in patients with neurogenic intermittent claudication caused by lumbar spinal stenosis and its relationship with age and body height in normal subjects. Methods: The study included 172 normal subjects (group C) (mean age 44.1 ± 16.6 years; mean height 163.7 ± 8.9 cm). Forty-seven patients (group L) (mean age 71.3 ± 8.7 years; mean height 158.8 ± 11.2 cm) underwent surgery because of neurogenic intermittent claudication in cauda equina type of lumbar spinal stenosis. Motor-evoked potentials from the abductor hallucis were recorded. Magnetic stimulation was delivered at the S1 spinous process. Compound muscle action potentials (CMAPs) and F-waves were also recorded after supramaximal electric stimulation of tibial nerves. The peripheral motor conduction time (PMCT) was calculated from the latencies of CMAPs and F-waves as follows: (CMAPs + F-waves − 1)/2. The CECT was calculated by subtracting the onset latency of the motor-evoked potentials from PMCT. Results: The mean values for F-wave latencies, motor-evoked potential latencies, and CECT were 44.5 ± 3.3, 20.6 ± 1.8, and 3.4 ± 0.8 milliseconds, respectively. F-wave and motor-evoked potential latencies showed significant positive linear correlations with age and body height. However, no significant correlation was found between CECT and age (P = 0.43) or body height (P = 0.26). Mean CECT was 5.7 ± 1.5 in group L. There was a significant difference between groups C and L (P < 0.05). Conclusions: The CECT value of normal subjects was 3.4 ± 0.8 milliseconds regardless of age and body height. We suggest that CECT may be a useful factor to consider when evaluating patients with neurogenic intermittent claudication.