Hiromichi Komori

The natural history of herniated nucleus pulposus with radiculopathy.

Study Design The present study retrospectively investigated the morphologic changes that occurred during conservative treatment of patients with unilateral leg pain resulting from herniated nucleus pulposus without significant lumbar canal stenosis. Objectives The results were correlated with clinical outcomes and extruding forms to determine which type of herniated nucleus pulposus had the greatest capacity for spontaneous regression and how rapidly such regression might occur. Summary of Background Data The study population consisted of 77 patients with radiculopathy. All patients complained primarily of unilateral leg pain, and 94% had positive tension signs. Additionally, 32% exhibited muscle weakness corresponding to the symptomatic nerve root. Methods All patients were studied more than twice using magnetic resonance imaging during conservative therapy at a mean interval of 150 days. Morphologic changes on magnetic resonance imaging fell into four categories, with herniated nucleus pulposus classified into three types using T1-weighted sagittal views. Each patient was reexamined on the same scanner; 53 patients were examined twice, and 24 patients were examined more than three times. Results Morphologic changes, with the exception of 13 false-negative cases, basically corresponded to clinical outcome. In half of the cases that showed some improvement at follow-up evaluation, improvement of clinical findings were seen before those observed on magnetic resonance imaging. Migrating herniated nucleus pulposus frequently presented an obvious decrease in size, and even disappearance in seven cases. The further the herniated nucleus pulposus migrated, the more decrease in size could be observed. The cases apparently corresponding to “protrusion” showed little or no change on follow-up magnetic resonance imaging. Regarding the mechanism of herniated nucleus pulposus disappearance, exposure to the vascular supply undoubtedly took a part, although many factors were suspected to have some influence. Conclusion Morphologic changes on magnetic resonance imaging mainly corresponded to clinical outcomes but tended to lag behind improvement of leg pain. Disappearance of herniate nucleus pulposus was seen frequently in the cases of migrating disc herniation, and it was presumed that exposure to the vascular supply had a lot to do with this phenomenon.

The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene

It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p < 0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly.

Upregulated expression of chemokines in herniated nucleus pulposus resorption.

Study Design Immunohistologic examination was performed on surgically removed samples of herniated nucleus pulposus. Objectives To determine what cell types predominate in the granulation tissues of herniated nucleus pulposus, and to elucidate whether chemokines are involved in the resorption process of herniated nucleus pulposus. Summary of Background Data The study population consisted of 30 patients suffering from herniated nucleus pulposus. Five macroscopically normal discs were obtained from spinal cord tumor and spinal cord injury managed with anterior discectomy (age range, 27‐63 years) as a healthy control group. Methods Immunohistochemical analysis was used to analyze the expression of chemokines. Results A marked infiltration of macrophage and vascular proliferation was identified with a T lymphocyte infiltration of mild degree in the granulation tissues. This tendency was more prominent in the exposed group compared with the nonexposed group. Infiltrating macrophages, fibroblasts, and endothelial cells in the granulation tissues strongly expressed monocyte chemotactic protein‐1 and macrophage inflammatory protein‐1α. Statistical analysis demonstrated that the exposed group was more abundant in Factor VIII, monocyte chemotactic protein‐1, and macrophage inflammatory protein‐1α positive cells than the unexposed group. Conclusions Inflammatory cells and their positivity for chemokines, such as monocyte chemotactic protein‐1 and macrophage inflammatory protein‐1α, are associated with blood vessels. Chemokines, such as monocyte chemotactic protein‐1 and macrophage inflammatory protein‐1α, were overexpressed in macrophages, fibroblasts, and endothelial cells, suggesting that these chemokines contribute to activation and recruitment of macrophages in a paracrine or autocrine fashion.

Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption.

Intervertebral disc herniation is a major cause of low back pain and sciatica. Spontaneous resorption of herniated disc (HD) is frequently detected by magnetic resonance imaging (MRI). Marked infiltration by macrophages and neo‐vascularization are observed upon histogical examination of HD. In addition, enhanced MRI studies suggest that HD resorption occurs more frequently in those completely exposed to the epidural space and that this correlates with their degree of vascularization. We have postulated that the angiogenic factor, vascular endothelial growth factor (VEGF), may be implicated in the neo‐vascularization of HD tissues. Here we demonstrate that VEGF and its receptors VEGFR‐1 and VEGFR‐2 are expressed in human surgical samples of HD. Using a co‐culture system comprised of murine peritoneal macrophages and intervertebral disc tissue as a model of the acute phase of HD developed previously, an increase in macrophage VEGF protein and mRNA expression was observed upon exposure to disc tissue. Tumor necrosis factor alpha (TNF‐α) was required for this induction of VEGF. Use of a novel angiogenesis assay revealed that addition of the conditioned media from the co‐culture system resulted in an increase of vascular tubule formation. This effect was strongly inhibited by anti‐VEGF antibody, but augmented by recombinant VEGF. We conclude that VEGF induction, under the co‐culture conditions tested can result in neo‐vascularization of intervertebral disc tissue and may thus play a role in the resorption of HD.

Dynamic motion study of the whole lumbar spine by videofluoroscopy

Study Design. Dynamic lumbar flexion‐extension motion was assessed by videofluoroscopy. Objectives. To identify the motion patterns of the whole lumbar spine in normal subjects and in patients with low back pain or spondylolisthesis during actual movement. Summary of Background Data. Assessment of lumbar instability on terminal radiographs is controversial. Information regarding spinal kinematics during actual movementin vivo is scarce. Methods. Fluoroscopic lumbar sagittal motion videos were recorded in volunteers (n = 13; mean age, 22.3) and in patients with chronic low back pain (n = 8; mean age, 43.5) and degenerative spondylolisthesis(n = 8; mean age, 63.1) while the subjects bent forward from a standing neutral position(eccentric motion) and then returned to the original position (concentric motion). The videos recorded approximately 8 seconds of motion and were converted to still images at 5 frames per second. Disc angles from the horizontal line were measured to estimate sagittal rotation of each segment. Disc degeneration was evaluated on T2‐weighted midsagittal magnetic resonance image. Results. In the volunteer group, six exhibited sequentially spreading motion, four exhibited simultaneous motion, and three showed an altered motion‐spreading pattern in the eccentric phase. The first two patterns were considered normal. Six (67%) of the patients with chronic low back pain also showed normal patterns, but seven (88%) of the patients with degenerative spondylolisthesis showed disordered patterns. The order of motion in the concentric phase was also different among the three groups. Prolonged deflection of the slipped segment was observed more frequently in the patients with degenerative spondylolisthesis. Disc degeneration was not always associated with motion‐spreading order and the motion patterns. Conclusion. Segmental instability influences the whole lumbar motion in patients with degenerative spondylolisthesis. The patients with chronic low back pain did not show a significant difference when compared with the volunteers.

Imaging of neural conduction block by neuromagnetic recording

OBJECTIVE For the clinical application of neuromagnetic recordings in neural conduction block, the patterns of magnetic fields in the region should be clarified. Using an experimental in vitro model, the spatiotemporal course of the neuromagnetic fields at the site of complete conduction block was examined. Additionally, the magnetic compound action fields (CAFs) and electric compound action potentials (CAPs) were compared and correlated. METHODS In a chamber containing Ringers solution, 10 isolated sciatic nerves of rabbits were electrically stimulated. Both evoked CAPs and CAFs were measured before and after the ligation of the nerve. The sequential positions of the current dipoles and the location of the conduction block were estimated by the least-squares search. RESULTS The magnetic contour maps of the CAFs showed a characteristic quadrupolar pattern propagating along the nerve. The peak of the leading magnetic field ceased and disappeared at the position of the nerve ligation, while the trailing magnetic field became attenuated before reaching that position. The positions of the conduction blocks were localized by magnetic recordings within a difference of 2mm. CONCLUSIONS The neuromagnetic recordings could visualize the change of the magnetic fields at the site of the complete conduction block and closely localize that position. SIGNIFICANCE The neural conduction block was visualized and localized by neuromagnetic recordings.

A new method of multisegment motor pathway monitoring using muscle potentials after train spinal stimulation

Study Design. Evoked muscle and nerve action potentials after spinal stimulation for intraoperative monitoring were investigated using a modified stimulation technique. Animal experiments and clinical application were performed. Objectives. To contrive a useful method of intraoperative motor pathway monitoring under inhalation anesthesia. Summary of Background Data. Many different kinds of procedures have been reported. No reliable method that reflects pure motor tract function has been established. Methods. Characteristic of our stimulating technique was the use of numbered consecutive pulses (“train stimulation”). In 16 cats, optimum condition of train stimulation, effects of anesthetic agents, and conductive pathway were examined. In 35 patients, muscle potentials evoked by train stimulation were recorded, and clinical usefulness was evaluated. Results. In the experimental study, the optimum stimulus condition was determined 1 ms interstimulous interval train of five pulses. Conductive pathway of this method was identified as a lateral column by selective spinal cord transection, In the clinical application, by using train stimulation, multisegmental muscle potentials were obtainable even using inhalation anesthetics. Conclusions. The facilitative effects of train stimulation, attributed to temporal summation, are considered to overcome the suppression of inhalation anesthesia. The evoked muscle potentials by train spinal stimulation reflect the functions of pure motor tract and is the only, extremely efficient method for intraoperative motor pathway monitoring.

Chemonucleolysis with human stromelysin-1.

Study Design. Immunohistologic analysis was performed on surgically removed samples of herniated nucleus pulposus to examine the expression of stromelysin‐1. We performed in vitro and in vivo experiments to determine whether recombinant human (rh) stromelysin‐1 is capable of degrading nucleus pulposus. Objective. To analyze the production of stromelysin‐1 in various types of herniated nucleus pulposus, and to examine the effects of this recombinant protein on nucleus pulposus tissues. Summary of Background Data. The authors previously demonstrated a progressive decrease in herniated nucleus pulposus size in some of the transligamentous and sequestration types of herniated nucleus pulposus using magnetic resonance imaging. An increased production of stromelysin‐1, a cartilage proteoglycan degrading enzyme, in herniated nucleus pulposus was reported recently. The authors speculated that if stromelysin‐1 is involved in the degradation of herniated nucleus pulposus, stromelysin‐1 itself may be used as a chemonucleolytic agent. Methods. Immunohistologic analysis using streptoavidin‐biotin method was performed on 20 herniated nucleus pulposus samples to investigate the expression of stromelysin‐1. Five herniated nucleus pulposus samples were incubated in a tissue culture medium in the presence or absence of rh stromelysin‐1. After 24 hours of incubation, their weight changes were measured, and the loss of proteoglycan was assessed by Safranin O staining. Rat nucleus pulposus tissues were obtained from coccygeal intervertebral discs, and autologous subcutaneous transplantation was performed. Rh stromelysin‐1 was injected into the grafted materials, and the reduction in size was followed by two‐dimensional measurements from the skin surface, using engineers calipers. Results. Immunohistologic analysis demonstrated the production of stromelysin‐1 in the granulation tissues of herniated nucleus pulposus. When stromelysin‐1 was injected into the murine nucleus pulposus tissues, they reduced in size more rapidly than the control group. In addition, human herniated nucleus pulposus materials obtained at surgery showed significant weight loss when treated with stromelysin‐1 in an organ culture system. Safranin O staining revealed extensive depletion of proteoglycan in these herniated nucleus pulposus samples. Conclusions. Stromelysin‐1 is a possible key enzyme in herniated nucleus pulposus resorption, and stromelysin‐1 may be a good candidate for use in chemonucleolysis. Administration of human stromelysin‐1 may physiologically facilitate the resorption process of herniated nucleus pulposus, increase the healing rate, and decrease complications after chemonucleolysis.

Functional recovery and regeneration of descending tracts in rats after spinal cord transection in infancy

Study Design. The functional recovery of rats that underwent spinal cord transection in infancy was evaluated by multimodal examination (functional tests, electrophysiologic evaluation, tract-tracing) to determine the basis for the recovery. Objectives. To determine whether the hind limb function in rats that underwent spinal cord transection in infancy is regained completely, which descending tracts regenerate after the transection, and whether the functional recovery is correlated with axonal reconnection. Summary of Background Data. It is widely accepted that a newborn rat recovers its hind limb function after spinal cord transection even without any specific treatments. This functional recovery might be attributed to possible regeneration of some descending pathways, although there is a counterargument that well-trained spinal cord reflexes may bring about functional compensation. Methods. The thoracic spinal cord of infant rats was completely transected at Th10 when they were 2 weeks of age. Multimodal functional tests and electrophysiologic studies were performed 5 weeks later. Some recovered rats (i.e., those able to walk after the transection) underwent spinal cord retransection, with subsequent reevaluation of locomotion and muscle-evoked potentials. At 6 weeks after the initial transection, tract-tracing studies were performed in some animals. Results. A motor performance score detected the functional differences between the control and the recovered rats. Muscle-evoked potentials of hind limbs after electrical stimulation to the brain were recorded in some of the recovered rats, but never in the unrecovered rats. Moreover, the muscle-evoked potentials of the recovered rats disappeared after spinal cord retransection that resulted in loss of voluntary movement. Morphologic studies in two rats provided evidence that reconnection of rubrospinal, vestibulospinal, and reticulospinal tracts had occurred, whereas corticospinal regeneration was not detected. Conclusions. It can be concluded that the hind limb function of rats that underwent spinal cord transection in infancy was partially regained; that axonal regeneration of the rubrospinal, vestibulospinal, or reticulospinal tracts was demonstrated, whereas the reconnection of the corticospinal tract was not observed; and that the axonal regeneration of these tracts is involved in the functional recovery.

Long-term outcomes of surgical treatment for tethered cord syndrome.

Surgical outcomes for tethered spinal cord syndrome (TCS) associated with low-lying conus medullaris were evaluated. We investigated the long-term results of untethering the spinal cord and dural plasty in surgical patients with a wide age range. Improvement of bladder dysfunction and suppression of leg deformity progression were noted in two pediatric patients. However, severe urinary dysfunction generally remained postoperatively. Adult patients commonly showed low back or leg pain as clinical manifestations. In seven adult patients, urinary dysfunction also improved. Neurologic findings and urinary deficits showed a favorable improvement mostly in adult TCS in comparison with natal or juvenile onset of TCS. A short duration from onset to surgery and cranial movement of the conus medullaris as assessed by postoperative magnetic resonance imaging were factors indicating a favorable prognosis.