Masafumi Kubota

Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias.

Study Design. The mechanisms responsible for the spontaneous regression of lumbar disc herniation (LDH) were studied by examining herniated tissue collected at operation from patients with LDH. Objective. The aim of the present study was to investigate the role of neovascularization and macrophages in hernias when spontaneous regression of LDH occurred. Summary of Background Data. Spontaneous regression of LDHs has already been demonstrated by diagnostic imaging with tools such as magnetic resonance imaging. However, there have been few studies on the mechanisms of spontaneous regression based on pathologic examination of herniated tissue. In particular, there has been no detailed work on the role of macrophages, which are thought to be closely associated with spontaneous regression. Methods. The magnetic resonance imaging and operative findings of 73 patients who underwent surgery were investigated, and specimens collected during surgery were examined by light and transmission electron microscopy. Results. Capillaries that invade the hernia and macrophages derived from monocytes migrating out of these capillaries are considered to be important factors in the regression of the herniated disc. Macrophages contain lysosomes filled with collagen-degrading enzymes that break down substances after phagocytosis, whereas primary lysosomes are secreted by these cells and break down intercellular substances such as collagen. Both of these mechanisms are closely involved in the regression of herniation. Conclusion. The inflammatory response that occurs around hernia tissue in the epidural space is believed to play an important role in herniated disc resorption, although it may also have a harmful effect on the adjacent nerve root. Therefore, control of the inflammatory reac-tion is an important challenge when treating patients with disc herniation.

Effects of arterial ischemia and venous congestion on the lumbar nerve root in dogs

The development of radiculopathy in patients with lumbar canal stenosis is thought to be closely related to intraradicular edema resulting from compression. However, there is little agreement as to question which is more essential for intermittent claudication: ischemia or congestion. The aim of the present experimental investigation was to examine the effect of ischemia and congestion on the nerve root using dogs. The aorta was clamped as an ischemia model of the nerve root and the inferior vena cava was clamped as a congestion model at the sixth costal level for 30 min using forceps transpleurally. Measurements of blood flow, partial oxygen pressure, and conduction velocity in the nerve root were repeated over a period of 1 h after release of clamping. Finally, we examined the status of intraradicular blood–nerve barrier under fluorescence and transmission electron microscope. Immediately after clamping of the inferior vena cava, the central venous pressure increased by about four times and marked extravasation of protein tracers was induced in the lumbar nerve root. Blood flow, partial oxygen pressure, and conduction velocity of the nerve root were more severely affected by aorta clamp, but this ischemia model did not show any intraradicular edema. The blood–nerve barrier in the nerve root was more easily broken by venous congestion than by arterial ishemia. In conclusion, venous congestion may be an essential factor precipitating circulatory disturbance in compressed nerve roots and inducing neurogenic intermittent claudication.

Motor neuron involvement in experimental lumbar nerve root compression: a light and electron microscopic study.

Study Design. The aim of this study is to investigate changes in lumbar motor neurons induced by mechanical nerve root compression using an in vivo model. This study is to investigate the changes of lumbar motor neuron induced by mechanical nerve root compression using in vivo model. Objectives. The effect of axonal flow disturbance induced by nerve root compression was determined in lumbar motor neuron. Summary of Background Data. The lumbar motor neuron should not be overlooked when considering the mechanism of weakness, so it is important to understand the morphologic and functional changes that occur in motor neurons of the spinal cord as a result of nerve root compression. However, few studies have looked at changes of neurons within the caused by disturbance of axonal flow, the axon reaction, chromatolysis, and cell death as a result of mechanical compression of the ventral root. Methods. In mongrel dogs, the seventh lumbar nerve root was compressed for 1 week, or 3 weeks using a clip. Morphologic changes of the motor neurons secondary to the axon reaction were examined by light and electron microscopy. Results. Light and electron microscopy showed central chromatolysis of motor neurons in the lumbar cord from 1 week after the start of compression. After 3 weeks, some neurons undergoing apoptosis were seen in the ventral horn. Conclusion. It is important to be aware that, in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression but also extends to the motor neurons within the lumbar cord as a result of the axon reaction. Patients with weakness of lower leg should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.

Lidocaine cytotoxicity to the zygapophysial joints in rabbits: changes in cell viability and proteoglycan metabolism in vitro.

Study Design. To examine whether lidocaine cytotoxicity to chondrocytes has been implicated in the development of osteoarthritis of the zygapophysial joints. Objective. This study was performed to determine the effects of varying concentrations and exposure times of lidocaine on the viability and proteoglycan metabolism of rabbit zygapophysial chondrocytes in vitro. Summary of Background Data. Zygapophysial joint injections are commonly administered with lidocaine for chronic spinal pain in orthopedic treatment. A lot of studies on the effect of zygapophysial joint injections are clinical, but many questions on the effect of lidocaine to zygapophysial chondrocytes remain unanswered. Methods. Cartilage was obtained from zygapophysial joints of adult rabbits. Chondrocytes in alginate beads were cultured in medium containing 6% fetal calf serum at 370 mOsmol at cell densities of 4 million cells/mL. They were then cultured for 24 hours under 21% oxygen with 0.125%, 0.25%, 0.5%, and 1% lidocaine, and without lidocaine as control. The cell viability profile across intact beads was determined by manual counting using fluorescent probes (LIVE/DEAD assay) and transmission electron microscopy. Lactate production was measured enzymatically as a marker of energy metabolism. Glycosaminoglycan (GAG) accumulation was measured using a modified dimethylmethylene blue assay. Results. Cell viability decreased in a time- and dose-dependent manner in the concentration range of 0.125% to 1.0% lidocaine under the confocal microscope. Under the electron microscope, apoptosis increased as the concentration of lidocaine increased. GAG accumulation/tissue volume decreases as the concentration of lidocaine increased. However, GAG produced per million cells and the rate of lactate production per live cell was significantly higher for cells cultured at 0.5% and 1% lidocaine than the control group. Conclusion. While these in vitro results cannot be directly extrapolated to the clinical setting, this data suggestcaution in prolonged exposure of zygapophysial cartilage to high concentration lidocaine.

Changes in Gait Pattern and Hip Muscle Strength After Open Reduction and Internal Fixation of Acetabular Fracture

OBJECTIVES To characterize changes in the gait pattern at 3 and 12 months after surgery for acetabular fracture, to assess the relationship between various gait parameters and hip muscle strength, and to determine the factors associated with gait disorders that correlate with gait parameters measured at 12 months after surgery. DESIGN Prospective cohort study. SETTING University hospital. PARTICIPANTS Patients (N=19) with acetabular fractures were treated by open reduction and internal fixation (ORIF) and examined at 3 and 12 months postoperatively. The study also included a similar number of sex- and age-matched control subjects. INTERVENTIONS Postoperative rehabilitation program. MAIN OUTCOME MEASURES Spatiotemporal, kinematic, and kinetic variables of gait and strength of hip flexor, adductor, and abductor muscles at 3 and 12 months after ORIF. RESULTS Walking velocity at 3 months after ORIF was slower in the patients than in the control subjects; however, walking velocity at 12 months was similar in the 2 groups. Although most of the kinematic and kinetic variables showed recovery to control levels at 3 and 12 months after ORIF, recovery was incomplete for pelvic forward tilt and hip abduction moment even at 12 months after ORIF. The greatest loss of muscle strength was noted in the hip abductors, where the average deficit was 35.4% at 3 months and 24.6% at 12 months. There was a significant relationship between hip abductor muscle strength and hip abduction moment at 3 months (R(2)=.63); however, this relationship diminished at 12 months (R(2)=.14). The presence of associated injuries correlated with lack of recovery of the peak hip abduction moment. CONCLUSIONS Pelvic forward tilt and peak hip abduction moment showed incomplete recovery at 12 months after ORIF with subsequent conventional and home exercise rehabilitation programs. Our results suggest that improvement of hip abductor muscle strength in the early postoperative period could improve the peak hip abduction moment.

Microvascular system of the lumbar dorsal root ganglia in rats. Part II: neurogenic control of intraganglionic blood flow

OBJECT The dorsal root ganglion (DRG) should not be overlooked when considering the mechanism of low-back pain and sciatica, so it is important to understand the morphological features of the vascular system supplying the DRG. However, the neurogenic control of intraganglionic blood flow has received little attention in the past. The authors used an immunohistochemical technique to investigate the presence and distribution of autonomic and sensory nerves in blood vessels of the DRG. METHODS Ten Wistar rats were used. To investigate the mechanism of vasomotion on the lumbar DRG, the authors used immunohistochemical methods. Sections were incubated overnight with antisera to tyrosine hydroxylase (TH), aromatic L-amino-acid decarboxylase (AADC), 5-hydroxytryptamine, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SOM), neuropeptide Y (NPY), leucine-enkephalin, and cholineacetyl transferase (Ch-E). The avidin-biotin complex method was used as the immunohistochemical procedure, and the sections were observed under a light microscope. RESULTS In the immunohistochemical study, TH-, AADC-, SP-, CGRP-, VIP-, SOM-, NPY-, and Ch-E-positive fibers were seen within the walls of blood vessels in the DRG. This study revealed the existence of a comprehensive perivascular adrenergic, cholinergic, and peptidergic innervation of intraganglionic blood vessels, with a possible role in neurogenic regulation (autoregulation) of intraganglionic circulation. CONCLUSIONS The presence of perivascular nerve plexuses around intraganglionic microvessels suggests that autonomic nerves play an important role in intraganglionic circulation.

Blood flow analysis of compressed nerve root after intravenous injection of lipo-prostaglandin E1

Prostaglandin E1 (PGE1) is a potent vasodilator as well as an inhibitor of platelet aggregation and has therefore attracted interest as a therapeutic drug for lumbar canal stenosis. However, investigations in the clinical setting have shown that PGE1 is effective in some patients but not in others, although the reason for this is unclear. The aim of the present study was to measure changes in intraradicular blood flow after intravenous injection of lipo‐PGE1 (0.15 µg/kg) using a laser Doppler flow meter in control model and nerve root compression model. Then, the nerve root in which blood flow was measured was removed and examined histologically. Intravenous injection of lipo‐PGE1 also resulted in marked increase of blood flow in the uncompressed nerve roots of the control group, but caused minimal enhancement of blood flow at the sites of nerve root compression exhibiting Wallerian degeneration. It is concluded that lipo‐PGE1 has less effect on markedly degenerated nerve roots than it does on those that are normal.

Development of a Chronic Cervical Cord Compression Model in Rats: Changes in the Neurological Behaviors and Radiological and Pathological Findings

Cervical myelopathy is caused by chronic segmental compression of the spinal cord because of degenerative changes of the spine. However, the exact mechanisms of chronic cervical cord compression are not fully understood. The purpose of this study was to validate a new animal model of chronic cervical cord compression capable of reproducing the clinical course without laminectomy in rats. A polyethylene line attached to a plastic plate was fastened with three turns around the vertebral body of C4 in 1-month-old rats. After surgery, the polyethylene line grows deeper into the dorsal wall of the spinal canal along with the growth of the spinal canal and vertebral body, producing a gradual compression of the spinal cord. The results show that this cervical canal stenosis (CCS) model in rats caused motor deficits and sensory disturbances 9 months after initiating CCS; however, no clinical manifestations took place until 6 months. The intramedullary high-intensity area on T2-weighted images was observed in 70% of the CCS model rats at 12 months after initiating CCS. In histological sections, the spinal cord was compressed along the entire circumference at 12 months after initiating CCS. The number of ventral neurons was decreased, and the white matter showed wallerian degeneration. This model might reproduce characteristic features of clinical chronic cervical cord compression, including progressive motor and sensory disturbances after a latency period and insidious neuronal loss, and represents chronic compression of the cervical spinal cord in humans.

Intraneural blood flow analysis during an intraoperative Phalen's test in carpal tunnel syndrome

Phalens test has been one of the most significant of clinical signs when making a clinical diagnosis of idiopathic carpal tunnel syndrome (CTS). However, it is unknown whether intraneural blood flow changes during Phalens test in patients with CTS. In this study, an intraoperative Phalens test was conducted in patients with CTS to observe the changes in intraneural blood flow using a laser Doppler flow meter. During Phalens test, intraneural blood flow showed a sharp decrease, which lasted for 1 min. Intraneural blood flow decreased by 56.7%–100% (average, 78.0%) in the median nerve relative to the blood flow before the test. At 1 min after completing the test, intraneural blood flow returned to the baseline value. After carpal tunnel release, there was no marked decrease in intraneural blood flow. This study demonstrated that the blood flow in the median nerve is reduced when Phalens test is performed in vivo.

Postoperative gait analysis and hip muscle strength in patients with pelvic ring fracture

The aims of present study were (1) to determine changes in kinematic and kinetic variables at 3 and 12 months after open reduction and internal fixation (ORIF) of pelvic ring fracture and (2) to determine the factor(s) associated with gait disorders that correlate with gait parameters measured at 12 months after surgery. Nineteen patients with pelvic ring fractures underwent ORIF and examined at 3 and 12 months postoperatively. The study also included a similar number of age-matched control subjects. Peak hip abduction angle, peak hip extension moment in the stance, peak hip abduction moment, and peak ankle plantarflexion moment at 3 months after ORIF were significantly lower than the respective control values. At 12 months, complete recovery was noted in peak hip abduction moment and peak ankle plantarflexion moment, whereas the recovery in peak hip abduction angle and peak hip extension moment in the stance was partial. The existence of neurological lesions and strength asymmetry of hip abductor and adductor at 3 months post-ORIF correlated with decreased peak hip abduction moment after ORIF. Our results highlighted characteristic gait patterns up to 12 months after ORIF for pelvic fracture, and these patterns correlated with neurological lesion and weakness of hip abductor and adductor muscles.