Hidezo Yoshizawa

Vasogenic edema induced by compression injury to the spinal nerve root : distribution of intravenously injected protein tracers and gadolinium-enhanced magnetic resonance imaging

The function of the blood-nerve barrier appears quite unique in the nerve root. Protein tracers that were injected into the subarachnoid space passed through the nerve root sheath and entered into the capillary lumen in the endoneurial space but tracers that were injected intravenously did not appear in the endoneurial space. Marked extravasation of protein tracers in the nerve root was induced at the compressed part by strong compression (60 gram force, 30 gram force) and capillaries in the nerve root showed opening of the tight junction accompanied by an increase in vesicular transport under the electron microscope. This situation was reflected as high intensity on Gadolinium-enhanced magnetic resonance imaging. In twenty-one of fifty patients with lumbar disc herniation, the affected nerve root was strongly enhanced by Gadolinium-diethylene-triaminepentaacetic acid, indicating that the blood-nerve barrier in the affected nerve root was broken and intraradicular edema was produced in these cases.

Chronic nerve root compression : pathophysiologic mechanism of nerve root dysfunction

Study Design. The pathophysiologic changes of the spinal nerve root caused by chronic compression were assessed in the lumbar spine of the adult dog. Methods. The seventh lumbar nerve root was banded with a Silastic tube 5 mm long and a 3 mm internal diameter, which is slightly larger than the diameter of the nerve root. Histologic and electrophysiologic studies as well as assessment of the blood-nerve barrier function in the nerve root were conducted at 24 hours through 12 months. Results. The earliest findings were thickening of the dura mater and arachnoid membrane around the affected nerve root corresponding to the alteration of the blood-nerve barrier in the nerve root after 1 month. After 3 months, large myelinated fibers decreased in number and small newly formed fibers increased in the periphery of the fascicle. At 6 months, endoneurial fibrosis and Wallerian degeneration of nerve fibers became obvious. Compound action potentials and sensory nerve conduction velocity decreased by 3 and 12 months, respectively. Decrease in amplitude of the compressed action potential was identical to the period of decrease in large myelinated fibers, and nerve conduction velocity did not decrease as long as some large myelinated fiber remained until 12 months after tubing. Conclusion. Intraradicular edema caused by alteration of the blood-nerve barrier is the most important factor in the nerve root dysfunction due to chronic compression.

Pathology of lumbar nerve root compression. Part 2: morphological and immunohistochemical changes of dorsal root ganglion.

Study design: This study is to investigate the changes of dorsal root ganglion (DRG) induced by mechanical compression using in vivo model.

Pathology of lumbar nerve root compression Part 1: Intraradicular inflammatory changes induced by mechanical compression

Study design: This study is to investigate the intraradicular inflammation induced by mechanical compression using in vivo model.

Changes in Nerve Root Motion and Intraradicular Blood Flow During an Intraoperative Straight-Leg-Raising Test

Study Design. An intraoperative straight-leg-raising (SLR) test was conducted to investigate patients with lumbar disc herniation to observe the changes in intraradicular blood flow, which then were compared with the clinical features. Objective. The legs of each patient were hung down from the operating table as a reverse SLR test during surgery, and intraradicular blood flow was measured. Summary of Background Data. It is not known whether intraradicular blood flow changes during the SLR test in patients with lumbar disc herniation. Methods. The subjects were 12 patients with lumbar disc herniation who underwent microdiscectomy. The patients were asked to adopt the prone position immediately before surgery, so that their legs hung down from the operating table. A reverse SLR test was performed to confirm the angle at which sciatica developed. During the operation, the nerve roots affected by the hernia were observed under a microscope. Then the needle sensor of a laser Doppler flow meter was inserted into each nerve root immediately above the hernia. The patient’s legs were allowed to hang down to the angle at which sciatica had occurred, and the change in intraradicular blood flow was measured. After removal of the hernia, a similar procedure was repeated, and intraradicular blood flow was measured again. Results. Intraoperative microscopy showed that the hernia was adherent to the dura mater of the nerve roots in all patients. The intraoperative reverse SLR test showed that the hernia compressed the nerve roots, and that there was marked disturbance of gliding, which was reduced to only a few millimeters. During the test, intraradicular blood flow showed a sharp decrease at the angle that produced sciatica, which lasted for 1 minute. Intraradicular flow decreased by 40% to 98% (average, 70.6% ± 20.5%) in the L5 nerve root, and by 41% to 96% (average, 72.0% ± 22.9%) in the S1 nerve roots relative to the blood flow before the test. At 1 minute after completion of the test, intraradicular blood flow returned to the value obtained at baseline. After removal of the hernia, all thepatients showed smooth gliding of the nerve roots during the second intraoperative test, and there was no marked decrease in intraradicular blood flow. Conclusions. This study demonstrated that the blood flow in the nerve root is reduced when the nerve root is compressed in vivo.

Effect of mechanical compression on the lumbar nerve root: localization and changes of intraradicular inflammatory cytokines, nitric oxide, and cyclooxygenase.

Study Design. Investigation of intraradicular inflammation induced by mechanical compression. Objective. To investigate the mechanism of nerve root pain, this study used a lumbar nerve root compression model. Summary of Background Data. The manifestation of pain at sites of inflammation has a close relationship with the release of mediators from macrophages. However, the mediators involved in inflammation of nerve roots as a result of mechanical compression remain almost unknown. Methods. In this study, the seventh lumbar nerve root of dogs was compressed with a clip for 3 weeks to observe the changes caused by compression. Immunohistochemistry was performed using the avidin-biotin-peroxidase complex method to observe the changes of T cells (CD45) and macrophages (Mac-1) after compression. Antibodies against as interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (i-NOS), and cyclooxygenase (COX)-1 and 2 were used to examine the localization and changes of these mediators caused by nerve root compression. Results. In control animals, resident T cells were detected, but there were no macrophages. IL-1β and COX-2 were positive in the Schwann cells and vascular endothelial cells, while COX-1 was detected in the vascular endothelial cells. However, no cells showed TNF-α or i-NOS positively. After nerve root compression, numerous T cells and macrophages appeared among the demyelinized nerve fibers. The macrophages were positive for IL-1β, TNF-α, i-NOS, and COX-2. Conclusion. Inflammatory cytokines, NO, and COX-2 may be deeply involved in radiculitis caused by mechanical compression, and these mediators seem to be important in the manifestation of root pain.

Effects of compression on intraradicular blood flow in dogs

In order to study the pathogenesis of radiculopathy, the authors investigated the effects of mechanical compression of the intraradicular blood flow in adult dogs using the electrochemically generated hydrogen washout method. The blood flow was more severly disturbed at the proximal side than the distal side when the nerve root was compressed, but when the clamp was released, the blood flow on the proximal side was almost completely restored, whereas the flow on the distal side did not recover and stayed at the reduced level. These phenomena can be explained both by the direction of blood flow in the radicular vessels and by the peculiar structure of the nerve root, which is soaked in cerebrospinal fluid.

Long-term follow-up study of posterior lumbar interbody fusion.

To see whether degenerative changes of the adjacent disks are accelerated by fixation of a lumbar segment, 48 patients who had undergone posterior lumbar interbody fusion (PLIF) more than 5 years previously were investigated radiographically and clinically. Narrowing of disk spaces was observed in 31% of the subjects, but it usually occurred at levels proximal to the fusion. The incidence of adjacent disk narrowing was not significantly higher after PLIF, compared with reports on degenerative changes of lumbar disks with aging. Some subjects showed narrowing of disks that were not adjacent to the fused level, suggesting that individual predisposition played a role in disk narrowing. Instability was not seen in any of the subjects. New development or elongation of the traction spurs at adjacent segments occurred at the disks proximal to the fusion. The clinical results were generally satisfactory, despite progression of degenerative changes on radiographs.

Anorectal and bladder function after sacrifice of the sacral nerves.

Study Design. The quantitative changes in anorectal and bladder functions after sacrifice of the sacral nerves were assessed. Objectives. To evaluate the bladder and anorectal functions before and after sacral nerve division in patients with sacral bone tumors. Summary of Background Data. The quantitative changes in bladder and anorectal functions after sacrifice of the sacral nerves have not been intensively studied. The purpose of this investigation was to measure the bladder and anorectal function before and after sacral nerve division using manometry and cystometry. Methods. Surgical resection of a sacral tumor was performed in five patients. The sacral nerves were sacrificed bilaterally in three patients and unilaterally in two patients. Anorectal function was evaluated on the basis of symptoms and physiologic tests. Micturition function was evaluated based on symptoms, and intravesical pressures were measured by cystometry. Results. The two patients with unilateral sacral nerve loss did not experience subjective problems with defecation or micturition, although the residual volume of urine was increased after surgery. Two of the three patients with bilateral sacral nerve loss had no urge to defecate, were unable to differentiate between feces and flatus, and experienced no urgency. Fecal incontinence was uncommon because of firm feces. It was possible to control defecation using enemas on alternate days. The third patient underwent colostomy because the maximum resting pressure, which is controlled by the hypogastric nerves, was affected before surgery. Conclusion. Unilateral sacrifice of sacral nerves results in little bladder or anorectal dysfunction.

Effect of lumbar nerve root compression on primary sensory neurons and their central branches: changes in the nociceptive neuropeptides substance P and somatostatin.

Study Design. This study examined the effect of lumbar nerve root compression on nociceptive neuropeptides in the axonal flow using an in vivo model. Objectives. The aim was to investigate changes in axonal flow after nerve root compression by using immunohistochemical techniques to detect substance P (SP) and somatostatin (SOM), which is thought to be involved in temperature and pain sensation. Summary of Background Data. Disturbance of intraradicular blood flow and nerve fiber deformation caused by mechanical compression are thought to be involved in the pathophysiology of diseases characterized by radicular symptoms, such as lumbar disc herniation and lumbar canal stenosis. However, little research has been conducted into the changes of axonal flow associated with nerve root compression. Methods. In dogs, the lumbar nerve roots were compressed using four types of clips with different pressures. Changes of SP and SOM levels in the spinal dorsal horn, dorsal root, and dorsal root ganglions were examined immunohistochemically after compression for 24 hours or 1 week. Results. After compression for 24 hours, axonal flow in the dorsal root was impaired, accumulation of SP and SOM was observed distal to the site of compression, and there was a decrease in the number of dorsal root ganglion cells showing positively for these neurotransmitters. Compression for 1 week resulted in a decrease in the number of SP- and SOM-positive fibers in the spinal dorsal horn. Conclusion. Change of axonal flow resulting from direct nerve compression could affect the metabolism of neurotransmitters that flow inside the axons and may be a primary cause of the decline in nerve function.