Spinal cord reconstruction using NeuroGel implants and functional recovery after chronic injury.

There is currently a lack of effective ways to achieve functional tissue repair of the chronically injured spinal cord. We investigated the potential of using NeuroGel, a biocompatible polymer hydrogel, to induce a reconstruction of the rat spinal cord after chronic compression-produced injury. NeuroGel was inserted 3 months after a severe injury into the post-traumatic lesion cavity. Rats were placed in an enriched environment and the functional deficits were measured using the BBB rating scale. A significant improvement in the mean BBB scores was observed. Rats without enriched environment and severely injured rats with an enriched environment alone showed no improvement; however, 7 months after reconstructive surgery using NeuroGel, a reparative neural tissue had formed within the polymer gel that included myelinated axons and dendro-dendritic contacts. NeuroGel implantation into a chronic spinal cord injury therefore resulted in tissue reconstruction and functional improvement, suggesting that such an approach may have therapeutic value in the repair of focal lesions in humans.

Exuberant transverse ligament degeneration causing high cervical myelopathy.

Two patients with cervical myelopathy and C1-C2 retro-odontoid masses were examined. Preoperative magnetic resonance imaging studies suggested soft tissue pannus, as might be seen in rheumatoid arthritis; however, the results of serologic testing for rheumatoid factor were negative in both patients. Intraoperative findings and pathologic examination revealed degenerative fibrocartilage without inflammation or neoplasia. Similar lesions reported in the literature have been described as retro-odontoid disk hernia, damaged transverse ligaments, transverse ligament degeneration, synovial cysts, ganglion cysts, and degenerative articular cysts. These lesions may share a common pathophysiologic origin and represent a single disease process, namely exuberant degeneration of the transverse ligament.

Dorsal arachnoid web with spinal cord compression: variant of an arachnoid cyst? Report of two cases.

Spinal arachnoid cysts are diverticula of the subarachnoid space that may compress the spinal cord; these lesions are most commonly found in the thoracic spine. Two patients who presented with thoracic myelopathy were noted on magnetic resonance imaging to have focal indentation of the dorsal thoracic cord, with syringomyelia inferior to the site of compression. Both patients were found at operation to have discrete arachnoid "webs" tenaciously attached to the dura mater and pia mater. These webs were not true arachnoid cysts, yet they blocked the flow of cerebrospinal fluid (CSF) and caused focal compression of the spinal cord. The mass effect appeared to be the result of a pressure gradient created by the obstruction of CSF flow in the dorsal aspect of the subarachnoid space. Both patients responded well to resection of the arachnoid web. Arachnoid webs appear to be rare variants of arachnoid cysts and should be suspected in patients with focal compression of the thoracic spinal cord.

Spinal cord hamartoma: case report.

OBJECTIVE AND IMPORTANCE: Spinal cord hamartomas are infrequently mentioned in the literature. The authors present a unique report detailing the clinical presentation of a spinal cord hamartoma, with supporting radiographic and pathological data. CLINICAL PRESENTATION: A 26-year-old man presented with progressive right upper extremity weakness. Imaging studies revealed an exophytic cervical spinal cord mass. INTERVENTION: Open biopsy was undertaken and revealed tethering of the lesion to the dura. A pathological examination revealed a spinal cord hamartoma. CONCLUSION: The patient's symptoms improved postoperatively, suggesting that tethering of the spinal cord was responsible for the symptoms. Although unusual, hamartoma should be included in the differential diagnosis of an exophytic spinal cord lesion.

The safety of OP-1 for lumbar fusion with decompression-- a canine study.

OBJECTIVE: Bone morphogenetic proteins can serve as adjuncts to autologous bone to achieve bony fusion, and recombinant BMPs such as osteogenic protein-1 (OP-1) have the potential to replace autologous bone altogether as fusion substrate. However, relatively little is known about the safety of OP-1 for spinal fusion procedures. This study examined the effects of OP-1 intentionally placed in the subarachnoid space following thecal sac decompression, and used as graft substrate in a canine dorsolateral lumbar spine fusion model. METHODS: Lumbar decompression with dorsolateral fusion was performed on 30 canines. The dura was opened to simulate an intraoperative rent and OP-1 was placed in the subarachnoid space and in the fusion bed. Animals were sacrificed after 16 weeks and the spines were examined manually, radiographically and pathologically. RESULTS: All animals treated with OP-1 developed new bone in the subarachnoid space. This bone compressed the spinal cord, but no clinical or pathological features of neurotoxicity were noted. Mild spinal stenosis was noted at the site of dural decompression in the OP-1 treated animals. Over 80% of animals treated with OP-1 developed fusion as assessed by palpation (52% by CT criteria), while only 25% of control animals fused. CONCLUSIONS: Recombinant human OP-1 is effective at promoting fusion in a canine dorsolateral lumbar spine fusion model. However, bone growth can occur over exposed, decompressed dura, and it can form in the subdural and subarachnoid spaces. The use of OP-1 as an adjunct to spinal fusion appears to have merit, but its use must be carefully controlled to avoid unwanted bone formation and subsequent neural compression.

The anatomical suitability of the C1-2 complex for transarticular screw fixation.

Posterior transarticular screw fixation of the C1-2 complex has become an accepted method of rigid internal fixation for patients requiring posterior C1-2 fusion. The principal limitation of this procedure is the location of the vertebral artery, because an anomalous position may prohibit screw placement. In this study, a consecutive series of computerized tomography (CT) scans was reviewed, and the suitability of each patient for transarticular screw fixation was evaluated. All of the fine-slice axial C1-2 CT scans and reconstructions performed on a spiral scanner over 2 years were reviewed. A novel screw trajectory reconstruction was designed to visualize the potential path of a transarticular screw in the plane of the reconstruction. Scans were reviewed for bone anatomy and the position of the transverse foramen. Seventeen (18%) of 94 patients had a high-riding transverse foramen on at least one side of the C-2 vertebra that would prohibit the placement of transarticular screws. The left side was involved in nine patients and the right in five. Three patients had bilateral anomalies. The mean age of the group with anomalies (35.9 years, range 10-76) was not significantly different from the overall mean age (35.7 years, range 6-94). An additional five patients (5%) were considered to have anatomy in which screw placement was feasible but risky. On the basis of these data, it is postulated that 18% to 23% of patients may not be suitable candidates for posterior C1-2 transarticular screw fixation on at least one side.

Biomechanical characteristics of C1-2 cable fixations.

The biomechanical characteristics of four different methods of C1-2 cable fixation were studied to assess the effectiveness of each technique in restoring atlantoaxial stability. Biomechanical testing was performed on the upper cervical spines of four human cadaveric specimens. Physiological range loading was applied to the atlantoaxial specimens and three-dimensional motion was analyzed with stereophotogrammetry. The load-deformation relationships and kinematics were measured, including the stiffness, the angular ranges of motion, the linear ranges of motion, and the axes of rotation. Specimens were nondestructively tested in the intact state, after surgical destabilization, and after each of four different methods of cable fixation. Cable fixation techniques included the interspinous technique, the Brooks technique, and two variants of the Gallie technique. All specimens were tested immediately after fixation and again after the specimen was fatigued with 6000 cycles of physiological range torsional loading. All four cable fixation methods were moderately flexible immediately; the different cable fixations allowed between 5 degrees and 40 degrees of rotational motion and between 0.6 and 7 mm of translational motion to occur at C1-2. The Brooks and interspinous methods controlled C1-2 motion significantly better than both of the Gallie techniques. The motion allowed by one of the Gallie techniques did not differ significantly from the motion of the unfixed destabilized specimens. All cable fixation techniques loosened after cyclic loading and demonstrated significant increases in C1-2 rotational and translational motions. The bone grafts shifted during cyclic loading, which reduced the effectiveness of the fixation. The locations of the axes of rotation, which were unconstrained and mobile in the destabilized specimens, became altered with cable fixation. The C1-2 cables constrained motion by shifting the axes of rotation so that C-1 rotated around the fixed cable and graft site. After the specimen was fatigued, the axes of rotation became more widely dispersed but were usually still localized near the cable and graft site. Adequate healing requires satisfactory control of C1-2 motion. Therefore, some adjunctive fixation is advocated to supplement the control of motion after C1-2 cable fixation (that is, a cervical collar, a halo brace, or rigid internal fixation with transarticular screws).

Radiographic and clinical follow-up review of Caspar plates in 49 patients.

Although they are excellent clinical tools, Caspar anterior cervical plates have not been studied closely with regard to their mechanisms of failure. As more extensive operations are contemplated on older, sicker patients, it is imperative to know when a plating system might be prone to failure and what the mechanism of that failure might be. Therefore, the authors reviewed 49 patients undergoing Caspar plate placement in whom sufficient radiographs were obtained to determine if the fate of the hardware was related to the patient's age, type of operation, and the length of construct. Eleven of 49 patients suffered hardware failure, defined as any amount of screw backout or breakage, plate pullout, or pseudarthrosis. Four patients underwent hardware removal; one underwent posterior fusion for pseudarthrosis. Only two required treatment in a halo brace. There was an eventual fusion rate of 100%, including one fibrous union, and one of the patients who underwent repeat surgery was lost to follow-up review. No graft extrusions or new neurological deficits were incurred as a result of hardware failure. Plate length predicted plate failure in a statistically significant manner. Increasing age and reoperation correlated with plate failure but were not statistically significant in this small number of patients. Telescoping of the bone graft and vertebral bodies, with concomitant migration of the plate and slippage of the screws, was common. However, telescoping was more profound in the group in which the plates failed. The authors conclude that Caspar plate failures are more likely to occur in the elderly and in patients who need longer constructs. Bone fusion can be expected even when the hardware loosens.

Thoracic vertebrectomy and reconstruction using a microsurgical thoracoscopic approach.

A video-assisted thoracoscopic microsurgical approach was developed in the laboratory and subsequently used clinically to resect abnormalities of the thoracic vertebrae, to decompress the thoracic spinal cord, and to reconstruct the thoracic vertebral bodies. This report describes the development of the clinical operative techniques for microsurgical thoracoscopic vertebrectomy, neural decompression, and spinal reconstruction. This minimally incisional approach was clinically used in 17 patients to treat vertebral osteomyelitis, tumors, and compression fractures. Microsurgical thoracoscopic techniques were performed using several narrow, flexible, working portals placed in small incisions in the intercostal spaces. Access to the thoracic spine was achieved through the pleural cavity after temporary deflation of one lung using a double-lumen endotracheal tube. The parietal pleura, segmental vessels, and rib heads were dissected off the surfaces of the involved vertebrae to expose the region of interest. Long narrow spine dissection tools were used to perform the spinal decommpression and reconstruction. This technique achieved the same amount of spinal dissection as that achieved with conventional open spinal procedures and used microsurgical visualization techniques. The small incisions with reduced soft tissue dissection may reduce postoperative pain, shorten the length of hospitalization, and have cosmetic and functional advantages. Thoracoscopic vertebrectomies and reconstruction of the spine were technically feasilble procedures that were performed with excellent clinical results. This minimally incisional technique provides a viable alternative to thoracotomy or to posterolateral approaches for thoracic vertebrectomy and vertebral body reconstruction.

Quantitative estimation of cryopreservation viability in rat fetal hippocampal cells.

Cryopreserved fetal tissue may be useful for neural grafting, but quantitation of yield is crucial for estimating cell transplant requirements. We have assessed cell survival and viability following dissociation, cryopreservation, and culture of rat fetal hippocampus to estimate cell yields at all stages of preparation. Hippocampal tissue from E17 fetal rats was dissected from the CNS and cryopreserved in toto after equilibration with 10% DMSO. Freshly dissociated tissue from contralateral hippocampi yielded a significantly greater number of cells per hippocampus than the cryopreserved tissue. Cell viability after dissociation and survival in culture was also significantly increased in the fresh hippocampi compared to that in the frozen group. Our results indicate that the overall cryopreservation cell yield at 24 h in culture is approximately 12% of the initial fresh tissue, taking these three factors into account. Though cryopreservation of fetal neural tissue for transplantation offers several practical advantages over immediate use, significant additional tissue may be required in comparison to fresh tissue to achieve a suitable quantity of live cells for grafting.

Relative risks of ventriculostomy infection and morbidity.

Ventricular catheter placement is a common procedure for the management of increased intracranial pressure. Hypotheses regarding the etiology of infection of catheters center on two alternative assumptions: 1) contamination leading to infection occurs at the time of catheter insertion, implying that catheter duration has minimal effect on infection risk; and 2) infection of catheters derives from catheter contamination after insertion, suggesting that duration of catheter use may significantly affect infection risk. We have studied the relative complication rate of ventricular catheter insertions using a retrospective approach (n = 161 patients and 253 catheter insertion procedures). The overall infection rate was 4.1%, but the daily infection hazard increased exponentially with time, to a maximum daily rate of 10.3% by day 6 of catheter insertion. This increasing risk appears most consistent with the second hypothesis. The risk of non-infectious complications was 5.6%, including hemorrhagic occurrences and misplacement severe enough to require a new catheter insertion. The daily hazard of infection approximately equalled the non-infectious risk of routine catheter replacement by day 5. Additional prospective data on the daily risk of CSF infection and the appropriateness of antibiotic prophylaxis either at the time of ventricular catheter insertion or continued through the catheter's presence may be required to both definitively identify which hypothesis of infection risk is correct and whether antibiotics can significantly ameliorate this risk.

Induction of neuronal morphology in adrenal chromaffin cells cocultured with denervated Schwann cells.

We have studied the interactions of adrenal chromaffin and Schwann cells in a coculture system to observe whether denervated Schwann cells induce and support chromaffin cell differentiation in a manner analogous to nerve growth factor (NGF). Schwann cells induce both the accumulation of intense clumps of cocultured chromaffin cells on their surfaces and intense neurite outgrowth. This interaction is not blocked by antibodies to NGF or laminin. Conditioned medium from Schwann cell cultures fosters neurite outgrowth in chromaffin cells in a fashion qualitatively similar to NGF. Our data indicate that denervated Schwann cells exert a profound aggregating and differentiating effect upon chromaffin cells, inducing the expression of a neuronal phenotype via a predominantly NGF-independent mechanism.

Fluorescent labeling of dissociated fetal cells for tissue culture.

The ability to pre-label cells used in transplantation experiments would have the potential benefits of identification of cell type and associated processes and the analysis of graft migration in the host. We have used an in vitro tissue culture system as a model to test several fluorescent dyes for this application. Fetal rat hippocampal tissue (E17-E18) was dissociated and incubated in the presence of carboxyfluorescein ester (CFSE), rhodamine-B dextran amine (RBD), DiI, or rhodamine-labeled latex microspheres. Cells were cultured in defined medium for up to 1 month. Cells labeled with CFSE were initially bright but faded over several days. RBD labeled the soma of cells, but fluorescence intensity was lost over a period of a few weeks. Cells labeled with DiI possessed brilliant staining of neuronal processes for weeks. Latex microspheres brightly labeled the soma but not the processes of neurons; fluorescent debris and sterility were problems with this label. We conclude that CFSE and DiI have significant potential usefulness in vitro as markers of cell viability and process formation with mammalian fetal CNS cells, whereas RBD is much less permanent. Latex microspheres may be suitable for pre-labeling of cells for transplantation if purification and sterility can be enhanced over present preparations.