Yutaka Hiraizumi

Open Total Dislocation of the Talus with Extrusion (Missing Talus): Report of Two Cases

Two different methods of treatment for open dislocation of the extruded talus without soft tissue attachments (missing talus) were examined. In case 1, a 20-year-old man sustained an open total dislocation of the talus due to a motorcycle accident. The missing talus was found within 3 hr and replaced after thorough washing and debridement. Weightbearing was permitted at 20 weeks; however, the density of the talar body increased in the x-ray and nonweightbearing status was resumed. Reexamination at 2 ½ years revealed that there was joint space narrowing on the x-ray and decreased pain with ambulation; the patient had returned to his job. In case 2, a 26-year-old man sustained an open total dislocation of the talus with a severe crush wound and impaired circulation to the foot. After thorough washing and debridement of the wound, the calcaneus and distal end of the tibia were aligned. The missing talus was found 3 days later, but not replaced. Weightbearing was allowed on the affected foot at 2 months; however, the patient felt pain at the joint surfaces and arthrodesis was consequently performed. At 2 ½ years, the patient had a 4.0-cm leg length discrepancy in the involved extremity, but felt no pain when walking. Although reduction of the talus is ideal to preserve function and length of the extremity, several complications can occur. A review of literature on open total dislocation of the talus with extrusion was performed.

Application of polyvinyl alcohol hydrogel membrane as anti-adhesive interposition after spinal surgery.

Study Design Three inflammatory and adhesive changes inside the spinal canal were analyzed histopathologically in cats. Objective To investigate the usefulness of a polyvinyl alcohol hydrogel sheet as an interposition over the dura to prevent inflammatory and adhesive reaction after laminectomy. Summary of Background Data A major concern after laminectomy is scar tissue formation that may result in extradural compression or make subsequent surgery to the same area difficult and hazardous. Methods Wide laminectomy was performed at L5 in 30 adult cats. The dura was covered with a polyvinyl alcohol hydrogel sheet, free fat graft, or without interposition as a control. Animals were killed at 3 or 12 weeks. Results In the control group, adhesion of the exposed dura was apparent. Thick, fibrous connective tissue was observed between the dura and the peravertebral muscles. In the fat graft group, the dura was separated from the scar tissue by living grafted fat. However, the dura was adherent to the grafted fat and fibroblasts migrated into the interstitial space. In the polyvinyl alcohol hydrogel group, only a thin synovium like layer was formed around the polyvinyl alcohol hydrogel sheet. Conclusions Polyvinyl alcohol hydrogel is made of water and alcohol, and has been shown to be nontoxic to tissues. This is permeable to low molecular weight, but impermeable to large cells such as fibroblasts. Thus, the polyvinyl alcohol hydrogel sheet prevents migration of inflammatory cells and subsequently reduces intraspinal canal scar tissue formation and adhesive reaction. Other beneficial properties are extreme elasticity and low friction, which elimlnate mechanical reaction to the spinal cord. The polyvinyl alcohol hydrogel sheet is believed to be useful in eliminating scar tissue formation and does not interfere with the dynamic gliding movement of the spinal cord and nerve roots.

Neuronal damage in rat brain and spinal cord after cardiac arrest and massive hemorrhagic shock

Objective:Severe global ischemia often results in severe damage to the central nervous system of survivors. Hind-limb paralysis is a common deficit caused by global ischemia. Until recently, most studies of global ischemia of the central nervous system have examined either the brain or spinal cord, but not both. Spinal cord damage specifically after global ischemia has not been studied in detail. Because the exact nature of the neuronal damage to the spinal cord and the differences in neuronal damage between the brain and spinal cord after global ischemia are poorly understood, we developed a new global ischemia model in the rat and specifically studied spinal cord damage after global ischemia. Further, we compared the different forms of neuronal damage between the brain and spinal cord after global ischemia. Design:Randomized, controlled study using three different global ischemia models in the rat. Setting:University research laboratory. Subjects:Male, adult Sprague-Dawley rats (300 g). Interventions:Animals were divided into three experimental groups, group A (n = 6, survived for 7 days), 12 mins of hemorrhagic shock; group B (n = 6, survived for 7 days), 5 mins of cardiac arrest; or group C (n = 6, each for 6 hrs, 12 hrs, 1 day, 3 days, and 7 days), 7 mins of hemorrhagic shock and 5 mins of cardiac arrest. Motor deficit of the hind limbs was studied 6 hrs to 7 days after resuscitation. Also, nonoperated animals (n = 6) were used as the control. Histologic analysis (hematoxylin and eosin, Fluoro-Jade B, terminal deoxynucleotidyl transferase- mediated dUTP end-labeling [TUNEL], Klüver-Barrera) and ultrastructural analysis using electron microscopy were performed on samples from the CA1 region of the hippocampus and lumbar spinal cord. Demyelination of the white matter of the lumbar spinal cord was analyzed semiquantitatively using Scion Image software. Main Results:No paraplegic animals were observed in either group A or B. All group C animals showed severe hind-limb paralysis. Severe neuronal damage was found in the CA1 region of the hippocampus in all groups, and the state of delayed neuronal cell death was similar among the three groups. Neuronal damage in the lumbar spinal cord was detected only in group C animals, mainly in the dorsal horn and intermediate gray matter. Demyelination was prominent in the ventral and ventrolateral white matter in group C. A significant difference was observed between control and group C rats with Scion Image software. Ultrastructural analysis revealed extensive necrotic cell death in the intermediate gray matter in the lumbar spinal cord in group C rats. Conclusion:The combination in the global ischemia model (i.e., hemorrhagic shock followed by cardiac arrest) caused severe neuronal damage in the central nervous system. Thereby, hind-limb paralysis after global ischemia might result from spinal cord damage. These results suggest that therapeutic strategies for preventing spinal cord injury are necessary when treating patients with severe global ischemia.

Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase-activating polypeptide (PACAP)

BackgroundAdult human mesenchymal stem/stromal cells (hMSCs) from bone marrow have been reported to exhibit beneficial effects on spinal cord injury (SCI). A neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is known to decrease neuronal cell death and inflammatory response after ischemia, SCI, and other neuronal disorders. Recently, we found that expression of the gene for mouse PACAP (Adcyap1) was greater in animals receiving hMSCs with neural injury such as ischemia. However, the association of PACAP with hMSCs to protect nerve cells against neural injuries is still unclear.MethodsWild-type and PACAP-gene-deficient (Adcyap1+/−) mice were subjected to spinal cord transection, and hMSCs (5 × 105 cells) were injected into the intervertebral spinal cord on day 1 post-operation (p.o.). Locomotor activity, injury volume, retention of hMSCs, mouse and human cytokine genes (which contribute to macrophage (MΦ) and microglial activation), and Adcyap1 were evaluated.ResultshMSCs injected into wild-type mice improved locomotor activity and injury volume compared with vehicle-treated mice. In contrast, non-viable hMSCs injected into wild-type mice, and viable hMSCs injected into Adcyap1+/− mice, did not. Wild-type mice injected with hMSCs exhibited increased Adcyap1 expression, and observed PACAP immunoreaction in neuron-like cells. Gene expression levels for IL-1, tumor necrosis factor α (TNFα), interleukin-10 (IL-10), and transforming growth factor β (TGFβ) decreased, while that for interleukin-4 (IL-4) increased, in hMSC-injected wild-type mice. In contrast, IL-1, TGFβ, and IL-4 gene expression levels were all abolished in hMSC-injected Adcyap1+/− mice on day 7 post-operation. Moreover, the mice-implanted hMSCs increased an alternative activating macrophage/microglial marker, arginase activity. The human gene profile indicated that hMSCs upregulated the gene of IL-4 and growth factors which were reported to enhance Adcyap1 expression. Finally, we demonstrated that hMSCs express human ADCYAP1 and its receptor gene after the inflammation-related interferon-γ (IFNγ) in vitro.ConclusionsThese results suggest that hMSCs attenuate the deleterious effects of SCI by reducing associated inflammatory responses and enhancing IL-4 production. This effect could be mediated in part by cell-cell cross-talk involving the neuropeptide PACAP.

Electrophysiologic Evaluation of Intermittent Sacral Nerve Dysfunction in Lumbar Spinal Canal Stenosis

Intermittent sacral nerve dysfunction, induced by walking In lumbar spinal canal stenosis, may cause symptoms including hyperesthesia and pain in perineum, urinary bladder incontinence, and penile erection. However, it is difficult to objectively document these symptoms. Evoked external urethral sphincter potentials by cones medullaris stimulation were measured bath before walking and after walking in five patients who complained of sexual organ or urinary dysfunction during walking, and were compared with simultaneously induced sacral nerve symptom s. These potentials were al so measured during surgery. Sacral nerve symptoms wore reproduced by talking 80–350 meters (Average 177.5 m]. These potentials disappeared In one patient end were decreased in four patients at the time when the claudicant symptoms disabled the patient during walking. The amplitude subsequently recovered In keeping with relief of those symptoms during rest. Monitoring of these potentials during surgery showed an increase of amplitude shortly after the decompression procedure of the cauda equina. In conclusion, this measuring method was valuable as an objective evaluation of intermittent sacral nerve dysfunction in lumber spinal canal stenosis.

Differences in Sensitivity Between Magnetic Motor-Evoked Potentials and Somatosensory-Evoked Potentials in Experimental Spinal Cord Lesions

Study Design Graded posterior spinal cord compression and partial sectioning of the spinal cord were performed, and magnetically induced descending spinal cord potentials were recorded. Objectives To compare the sensitivity of transcranial magnetic motor‐evoked potentials in the spinal cord and other spinal cord evoked potentials to spinal cord lesions. Summary of Background Data Somatosensory‐evoked potentials have been the standard technique for monitoring spinal cord function during spinal surgery. These potentials, however, do not necessarily reflect descending motor tract function. Transcranial electric or magnetic stimulation for motor‐evoked potentials is a more direct measure of motor tract function. However, more research on magnetic motor‐evoked potentials is needed. Methods Fifteen adult cats were used. Graded posterior spinal cord compression was performed at L2 in 10 cats, and partial sectioning of the spinal cord was performed at L2 in five cats. The location sequence of lesioning was dorsal column section, dorsal 1/2 section, dorsal 2/3 section, and total spinal cord section. Magnetic motor‐evoked potentials were recorded by epidural catheter electrodes placed above, at, and below the lesion. Electric motor‐evoked potentials and spinal and cortical somatosensory‐evoked potentials were recorded serially for a comparison of their sensitivity to spinal cord dysfunction. Results In posterior spinal cord compression, N1 amplitude of magnetic motor‐evoked potentials at and below the lesion decreased after 1 minute of compression with a 70 g weight, and N1 and N2 amplitude disappeared after 1 minute of compression with a 100‐ to 120‐g weight. Electric motor‐evoked potentials changed at amplitudes comparable with those shown by magnetic motor‐evoked potentials. Spinal somatosensory‐evoked potentials showed the most sensitive changes to spinal cord posterior compression and disappeared after 1 minute of compression with 80 g. Cortical somatosensory‐evoked potentials in five cats were not sensitive enough for spinal cord posterior compression injury and did not disappear even after 1 minute of compression with 120 g. In magnetic motor‐evoked potentials, after dorsal hemisectioning of the spinal cord only N3 disappeared; N1 and N2 disappeared after ventral spinal cord sectioning. In spinal somatosensory‐evoked potentials, amplitudes decreased after dorsal column sectioning, and all negative peaks disappeared after dorsal hemisectioning of the spinal cord. Conclusions Posterior compression injuries are diagnosed more easily with spinal somatosensory‐evoked potentials. Motor‐evoked potentials were slightly less sensitive, but they were significantly more useful in diagnosing posterior compression injuries than were cortical somatosensory‐evoked potentials.

The anti-inflammatory property of human bone marrow-derived mesenchymal stem/stromal cells is preserved in late-passage cultures.

Human mesenchymal stem/stromal cells (hMSCs) have been reported to improve neural damage via anti-inflammation and multi-differentiation abilities. Here, we investigated immunosuppression effects of hMSCs by mixed-culturing with interferon-γ (IFNγ) stimulated BV-2 mouse microglial cells. We show that hMSCs decreased nitrite oxide (NO) production from BV-2 cells in cell density dependent manner. Aged hMSCs and peroxisome proliferator-activated receptor-γ (PPARγ) knockdown hMSCs decreased differentiation abilities but maintained NO suppressive function. We finally confirmed NO suppression activities of hMSCs in IFNγ-stimulated primary microglia/macrophages. It suggested that hMSCs significantly modified NO production in activated phagocytes and it might be preserved in late passage cultures.

Long term observation of micturition by spinal cord transected rabbits

Neurogenic bladder was observed in chronic spinalized animals. Since these animals are difficult to maintain for long periods, there are few reports of systemic study of these preparations. We have recently observed micturition by spinalized rabbits over a period of 4 weeks. In thoracic or lumbar spinalized rabbits, urinary bladder contraction and external urethral sphincter activity were initially recorded from 1-2 days postoperative. Contraction coincided with appearance of hind-limb spasticity. This micturition was the so-called detrusor-external urethral sphincter dyssynergy with residual urine. In sacral spinalized rabbits, no micturition reflex, external urethral sphincter activity, or hind-limb spasticity were observed and the flaccid state continued for 4 weeks. It is suggested that a segmental micturition reflex pathway exists initially in the rabbit sacral cord, because reappearance of the micturition reflex was extremely quick (1-2 days) compared to that of cats (2-3 weeks). Animal hypnosis enabled immobilization during measurement without anesthetic or decerebration. Chronic spinalized rabbits, which are very intolerant to spinal damage, can be maintained alive by intensive care at and post operation and are useful for systemic study of spinal cord injury.

Regional lung perfusion and ventilation with radioisotopes in cervical cord-injured patients.

In general, cervical cord-injured patients present with restrictive pulmonary dysfunction resulting from paralysis of the intercostal muscles. Vital capacity frequently decreases below 50% of that in normal subjects, and their respiratory pattern frequently includes paradoxical movement in which the intercostal spaces sink and the abdomen distends at inspiration. Ventilation scintigraphy using Xe-133 and pulmonary perfusion scintigraphy using Tc-99m macroaggregated albumin (MAA) were performed on nine cervical cord-injured patients and four normal subjects to investigate regional lung functions in the cervical cord-injured patients. 1) Pulmonary perfusion scintigraphy, in which measurement was made in the supine position, revealed no differences between the patients and the normal subjects. 2) The inhomogeneous ventilation/ perfusion distribution was presumed to have resulted from change in regional intrapleural pressure due to paradoxical movement of the thoracic cage. 3) Washin and washout times were prolonged by paralysis of the intercostal muscles. These phenomena were particularly apparent in the upper and middle lung regions where compensating action by movement of the diaphragm is small.

Long-term morphology of spastic or flaccid muscles in spinal cord-transected rabbits

Despite difficulty in long-term maintenance of spinalized rabbits, muscular pathologic changes in chronic spinalized rabbits could be observed for a period of four weeks. Rabbits were prepared by spinal cord transection at T10 (spastic paralysis) or by spinal cord removal below L7 (flaccid paralysis). Spastic preparations showed hind-limb spasticity and reflex incontinence one to two days after operation. Hypertrophic fibers began to appear in spastic muscles after two weeks. This hypertrophy, thought to be caused by phasic repetitive contraction, was verified by electron microscopy to be different from normal exercise hypertrophy. Flaccid preparations maintained hind-limb flaccidity and overflow incontinence. In flaccid muscle, marked muscle fiber necrosis indicated rapid atrophy. Spinal deformity and joint contracture inactivate spinalized rabbits, and cause pressure sores. However, feeding assistance and avoidance of complications make long-term maintenance possible.