Keiichiro Shiba

Effects of the Second National Acute Spinal Cord Injury Study of high-dose methylprednisolone therapy on acute cervical spinal cord injury-results in spinal injuries center.

Study Design. Retrospective single-center study. Objective. To evaluate the recovery of motor function and the early complications in patients with acute cervical spinal cord injury after receiving a high dose of methylprednisolone sodium succinate (MPSS) within 8 hours of injury. Summary of Background Data. High-dose MPSS therapy has been demonstrated to improve the neurologic recovery in patients with acute spinal cord injury. However, it remains a controversial treatment. Methods. Seventy patients were included in this study: 37 in the MPSS group who were treated with MPSS within 8 hours of their injury according to the Second National Acute Spinal Cord Injury Study protocol, and 33 in non-MPSS group who were not administered with MPSS. Improvements in the American Spinal Injury Association motor score were compared between the MPSS group and the non-MPSS group. In patients with complete motor loss at admission and follow-up periods, improvements of myotomal levels between the MPSS (n = 15) and non-MPSS groups (n = 21) were compared. Early complications within 6 weeks of high-dose MPSS therapy were compared with those of no MPSS therapy. Results. Among the patients with incomplete paralysis at admission, the American Spinal Injury Association motor scores in the MPSS group were improved more significantly than those in the non-MPSS group at 6 weeks and 6 months after injury. Meanwhile, among the patients with complete paralysis at admission, the patients in the MPSS group did not show significantly more change in motor score than those in the non-MPSS group. Improvement in myotomal level had no significant difference between the MPSS and non-MPSS groups. The MPSS group had 10 patients with early complications, while the non-MPSS group had 14. The differences between the 2 groups showed no statistical significance. Conclusions. MPSS should be administered to patients with incomplete cervical spinal cord injury according to the Second National Acute Spinal Cord Injury Study protocol.

Outcome of decompression surgery for cervical spinal cord injury without bone and disc injury in patients with spinal cord compression: a multicenter prospective study

Study design:A multicenter prospective study comparing the neurological outcome of patients treated by surgical intervention versus conservative treatment for cervical spinal cord injury (CSCI) without bone and disc injury.Objective:To evaluate the neurological outcome of decompression surgery for CSCI without bone and disc injury in patients with spinal cord compression with incomplete paralysis (AIS B, C).Setting:The Japan LHWO Spinal Injuries Center and the other 10 labor accident hospitals in Japan.Methods:Thirty-four patients with AIS B, C and cervical spinal cord compression were classified into either a surgical treatment group or a conservative treatment group. The 34 patients enrolled were equally divided between the groups. Patients with AIS B, C and mild spinal compression were enrolled into another group.Results:The neurological outcome of surgical treatment and conservative treatment for AIS B, C with spinal cord compression was found to be closely similar. In addition, the neurological outcome was also similar to that observed after conservative treatment for AIS B, C in patients presenting with mild spinal cord compression.Conclusions:Surgical treatment was not found to be superior to conservative treatment for CSCI patients without bone and disc injury suffering from spinal cord compression in the acute phase.

Therapeutic Activities of Engrafted Neural Stem/Precursor Cells Are Not Dormant in the Chronically Injured Spinal Cord

The transplantation of neural stem/precursor cells (NSPCs) is a promising therapeutic strategy for many neurodegenerative disorders including spinal cord injury (SCI) because it provides for neural replacement or trophic support. This strategy is now being extended to the treatment of chronic SCI patients. However, understanding of biological properties of chronically transplanted NSPCs and their surrounding environments is limited. Here, we performed temporal analysis of injured spinal cords and demonstrated their multiphasic cellular and molecular responses. In particular, chronically injured spinal cords were growth factor‐enriched environments, whereas acutely injured spinal cords were enriched by neurotrophic and inflammatory factors. To determine how these environmental differences affect engrafted cells, NSPCs transplanted into acutely, subacutely, and chronically injured spinal cords were selectively isolated by flow cytometry, and their whole transcriptomes were compared by RNA sequencing. This analysis revealed that NSPCs produced many regenerative/neurotrophic molecules irrespective of transplantation timing, and these activities were prominent in chronically transplanted NSPCs. Furthermore, chronically injured spinal cords permitted engrafted NSPCs to differentiate into neurons/oligodendrocytes and provided more neurogenic environment for NSPCs than other environments. Despite these results demonstrate that transplanted NSPCs have adequate capacity in generating neurons/oligodendrocytes and producing therapeutic molecules in chronic SCI microenvironments, they did not improve locomotor function. Our results indicate that failure in chronic transplantation is not due to the lack of therapeutic activities of engrafted NSPCs but the refractory state of chronically injured spinal cords. Environmental modulation, rather modification of transplanting cells, will be significant for successful translation of stem cell‐based therapies into chronic SCI patients. STEM Cells 2013;31:1535–1547

A New Clinical Evaluation for Hysterical Paralysis

Study Design. A cross-sectional study was performed to elucidate the usefulness of a new clinical evaluation, and a prospective study was performed to detect hysterical paralysis using this evaluation method. Objectives. To make a correct diagnosis of hysterical paralysis, a new clinical evaluation was developed. Summary of Background Data. Hysterical paralysis is a conversion disorder. Its diagnosis must be ruled out when encountering a patient with paralysis, therefore imaging and electrophysiological studies are often necessary, but costly. The principal salient diagnostic features for diagnosing hysterical paralysis are thought to be the preservation of a normal reflex pattern, normal rectal sensation, and normal bladder and bowel functions; however, these features are not always successfully identified. Methods. A new clinical evaluation named the “Spinal Injuries Center” test was developed. The lower extremities of the patients were divided into two groups as follows: in group A, the patients were able to lift up the knee; in group B, the patients were unable to lift up the knee. The 96 legs of the 48 patients who had obvious myelomalacia were randomly chosen. All legs were investigated using the Spinal Injuries Center test, and the association between each group and the Spinal Injuries Center test was examined. The 28 legs of the 14 patients in whom hysterical paralysis was diagnosed were prospectively evaluated using the Spinal Injuries Center test, and the association between the groups and the Spinal Injuries Center test was examined. Results. Forty-eight legs were classified as group A, and 48 legs were classified as group B. In group A, 45 legs were judged to be positive for the Spinal Injuries Center test, and 3 legs were negative. In group B, 1 leg was judged to be positive for the Spinal Injuries Center test, and 47 legs were negative. All legs of the patients with hysterical paralysis were classified as group B; however, all legs were positive for the Spinal Injuries Center test. Conclusions. The Spinal Injuries Center test is a newclinical evaluation method that can help make a correct diagnosis of hysterical paralysis. When a patient is unable to lift up his knees by himself, the result of the Spinal Injuries Center test is considered to be positive, and hysterical paralysis is diagnosed in such patients. The diagnosis of hysterical paralysis must be ruled out when encountering patients with paralysis, and as a result, imaging and electrophysiological studies are often necessary. Unfortunately, such tests are costly. Thus, a new clinical evaluation for the diagnosis of hysterical paralysis, named the Spinal Injuries Center test, was developed. When patients who are unable to lift up their knees by themselves test positive using the Spinal Injuries Center test, then they are considered to have ether hysterical or simulated paralysis.

Does ossification of the posterior longitudinal ligament affect the neurological outcome after traumatic cervical cord injury

Study Design. Retrospective outcome measurement study. Objectives. The purpose of this study is to assess whether ossification of the posterior longitudinal ligament (OPLL) affects neurologic outcomes in patients with acute cervical spinal cord injury (SCI). Summary of Background Data. There have so far been few reports examining the relationship between OPLL and SCI and there is controversy regarding the deteriorating effects of OPLL-induced canal stenosis on neurologic outcomes. Methods. To obtain a relatively uniform background, patients nonsurgically treated for an acute C3–C4 level SCI without any fractures or dislocations of the spinal column were selected, resulting in 129 patients. There were 110 men and 19 women (mean age was 61.1 years), having various neurologic conditions on admission (American Spinal Injury Association [ASIA] impairment scale A, 43; B, 16; C, 58; D, 12). The follow-up period was the duration of their hospital stay and ranged from 50 to 603 days (mean, 233 days). The presence of OPLL, the cause of injury, the degree of canal stenosis (both static and dynamic), and the neurologic outcomes in motor function, including improvement rate, were assessed. Results. Of the 129 patients investigated in this study, OPLL was identified at the site of the injury in 13 patients (10.1%). In this OPLL+ group, the static and dynamic canal diameters at C3 and C4 were significantly smaller than those of the remaining 116 patients (OPLL− group). However, no significant difference was observed between the 2 groups in terms of ASIA motor score both at the time of administration and discharge, and the mean improvement rate in ASIA motor score was 55.5 ± 9.0% in OPLL+ group, while it was 43.1 ± 2.8% in the OPLL−group. Furthermore, no significant correlation was observed between the static/dynamic canal diameters and neurologic outcome in all 129 patients. Conclusion. No evidence was found for OPLL to have any effect on the initial neurologic status or recovery in motor function after traumatic cervical cord injury, suggesting that the neurologic outcome is not significantly dependent on canal space.

Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans

Acute hyperglycemia exacerbates poor functional outcomes after spinal cord injury through overactivation of microglia in mice and in a human cohort. Treating Hyperglycemia After Spinal Cord Injury Spinal cord injury is a devastating disorder for which the identification of exacerbating factors is urgently needed. Kobayakawa et al. now report that acute hyperglycemia after spinal cord injury is an independent risk factor for poor functional outcome. They demonstrate that resident immune cells called microglia become overactivated after spinal cord injury when blood glucose concentrations are too high. This resulted in exacerbation of the inflammatory response and poor pathological and functional outcomes in mice and in humans with spinal cord injury. In contrast, manipulating blood glucose concentrations rescued poor functional outcomes after acute spinal cord injury in mice. These results suggest that glycemic control may be needed to improve recovery after acute spinal cord injury in human patients. Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor κB (NF-κB) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson χ2 analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ≥126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, −1.37; 95% confidence interval, −2.65 to −0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury.

Risk factors for missed dynamic canal stenosis in the cervical spine.

Study Design. Retrospective analysis of kinematic magnetic resonance (MR) images. Objective. To elucidate the distribution and risk factors associated with missed dynamic stenosis in cervical spine. Summary of Background Data. Motion of the cervical spine is widely accepted to be associated with cervical spondylotic myelopathy; however, the distribution and the risk factors for dynamic spinal stenosis are not well understood. Methods. A total of 435 symptomatic patients (2610 cervical segments) obtained upright kinematic MR images in neutral, flexion, and extension postures. Spinal cord compression (SCC), spondylolisthesis, disc bulging, angular motion, translational motion, disc degeneration grade, Modic changes, segmental alignment, and developmental stenosis were all evaluated. Cervical segments C2–C3 to C7–T1 were divided into 2 groups, determined by the presence of SCC. After excluding segments with SCC in the neutral position, a multivariate logistic regression model was used to evaluate for associated risk factors of SCC in flexion and extension that were not present in the neutral position. Results. SCC in neutral position was observed in 5.3% (139/2610) of segments. After excluding these segments, missed dynamic stenosis was found in 8.3% (204/2471) of segments in extension and 1.6% (40/2471) in flexion. Missed dynamic stenosis in both extension and flexion was most frequent at C5–C6. Multivariate logistic regression analysis for dynamic stenosis in extension revealed that disc bulge greater than 2.4 mm, angular motion greater than 4.8°, moderate and severe disc degeneration, segmental kyphosis, and developmental stenosis were significant risk factors. In flexion, significant risk factors were a disc bulge of 1.9 mm or greater, moderate to severe disc degeneration, and segmental kyphosis. Conclusion. Dynamic cord compression was most common at the C5–C6 segment. Cervical segments with greater disc bulge, more severe disc degeneration, greater angular motion, segmental kyphosis, and developmental stenosis may be at risk for missed dynamic stenosis. Level of Evidence: 2

Analysis of the risk factors for tracheostomy in traumatic cervical spinal cord injury.

Study Design. A retrospective, consecutive case series. Objective. To determine the risk factors that have a statistically significant association with the need of tracheostomy in patients with cervical spinal cord injury (CSCI) at the acute stage. Summary of Background Data. Respiratory complications remain a major cause of further morbidity and mortality in patients with CSCI. Although several risk factors for tracheostomy have been postulated in these patients, no definitive factors have yet been established according to a multivariate analysis. The use of vital capacity was considered as a single global measure of respiratory function in patients with spinal cord injury, but there are very few studies in which the forced vital capacity was investigated as a risk factor for tracheostomy. Methods. This study that reviewed the clinical data of 319 patients with CSCI, who were evaluated for their neurological impairment within 2 days after injury, was performed. We analyzed the factors postulated to increase the risk for tracheostomy, including patients age, neurological impairment scale grade and level, smoking history, pre-existing medical comorbidities, respiratory diseases, Injury Severity Score, forced vital capacity, and percentage of vital capacity to the predicted value (%VC), using a multiple logistic regression model and classification and regression tree analysis. Results. Of 319 patients, 32 patients received tracheostomy (10.03%). The factors identified using a multiple logistic regression model were high age (69 years of age or older), severe neurological impairment scale, low forced vital capacity (⩽500 mL), and low percentage of vital capacity to the predicted value (<16.3%). The decision tree analysis demonstrated that forced vital capacity, the severe neurological impairment scale, and high patient age were predictive of need for tracheostomy on 94.4% occasions. Conclusion. The measurement of forced vital capacity is indispensable to predict the need for tracheostomy in patients with CSCI at the acute stage.

The potential for functional recovery of upper extremity function following cervical spinal cord injury without major bone injury

Study Design:This was a retrospective observational study.Objectives:The objectives were to describe the prognosis of upper extremity function following cervical spinal cord injury (CSCI), and to identify prognostic factors for functional recovery.Setting:Spinal Injuries Center, Japan.Methods:Sixty patients with C3–4 CSCI without major bone injury participated in the study. Patients were treated nonsurgically and evaluated using the American Spinal Injury Association (ASIA) scales for the upper and lower extremities, their residual cervical motor functions, the modified Frankel grade and an upper extremity function scale. We compared the findings for the upper extremity function scale at 6 months with those for the residual cervical motor functions and modified Frankel grade obtained 3 days after injury.Results:Most patients with CSCI who could flex their hip and knee from a supine position (95%) or who showed some active elbow extension (86%) 3 days after their injury could use a spoon at 6 months. We compared patients who used their fingers at 6 months to those who could not, and observed significant differences in age and ASIA scores for the upper and lower extremities obtained 3 days after injury. A strong correlation was observed between the initial motor scores and the extent of functional recovery at 6 months.Conclusion:Hip and knee flexion from the supine position and elbow extension 3 days after injury significantly predicted a positive prognosis for upper extremity function. Younger age and higher ASIA motor scores obtained 3 days after injury were factors associated with neurological recovery.

Analysis of the risk factors for severity of neurologic status in 216 patients with thoracolumbar and lumbar burst fractures.

Study Design. A retrospective, consecutive case series. Objective. To determine the risk factors that have a significant correlation with the severity of neurologic impairment in thoracolumbar and lumbar burst fractures. Summary of Background Data. The correlation between spinal canal stenosis due to bony fragments and the severity of neurologic deficits in thoracolumbar and lumbar burst fractures remains controversial. Moreover, there have so far been no reports in the literature in which the risk factors (spinal canal stenosis and the disruption of posterior ligamentous complex) causing a severe neurologic deficit were analyzed using a multiple logistic regression model. Methods. A review of the clinical data (neurologic impairments on admission and a finding of posterior ligamentous complex disruption at the time of operation), axial computed tomography, and plain lateral radiography of 216 patients in thoracolumbar (T11–L1) and lumbar (L2–L5) burst fractures was performed. The factors related to neurologic impairments were analyzed using a multiple logistic regression model. Results. In all cases, both the spinal canal stenosis (P < 0.01) and disruption of posterior ligamentous complex (P < 0.01) were significant risk factors. Interestingly, these two risk factors varied according to the injury levels: at thoracic level, the spinal canal stenosis (P < 0.01); at the first lumbar spine, the disruption of the posterior ligamentous complex (P < 0.01); and at the lumbar spine below L2, both of the spinal canal stenosis (P < 0.01) and the disruption of posterior ligamentous complex (P < 0.05) were significant risk factors, respectively. Conclusion. In the patients with thoracolumbar and lumbar burst fractures, the significance of the two important risk factors related to clinical results, namely, the stenosis ratio of spinal canal and the disruption of posterior ligamentous complex, were found to vary depending on the level of injury.