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Adenoviral nerve growth factor and β-galactosidase transfer to spinal cord: a behavioral and histological analysis

Nicholas M. Boulis, Vikas Bhatia, Theodore I. Brindle, Harland T. Holman, Daniel J. Krauss, Mila Blaivas, and Julian T. Hoff

Object. The present study characterizes the time course and loci of gene expression induced by the administration of adenoviral vectors into spinal cord. Although a marked inflammatory response to these vectors occurred, no effect on spinal cord function was seen in the 1st postoperative week. The expression of transgenic genes delivered by viral vectors is being exploited throughout the nervous system. The present study utilized adenoviral vectors containing the Rous sarcoma virus (RSV) promoter and a nuclear localization signal to achieve transgenic expression in mammalian spinal cord.

Methods. Initial experiments utilizing the vector Ad.RSVlacZ (1012 particles/ml) injected into the region of the central canal resulted in viral gene expression stretching over approximately 1.2 cm of spinal cord. Gene expression was first detected 3 days following viral administration and lasted until postinjection Day 14 with peak expression at Day 7. A variety of cell types in both white and gray matter expressed lacZ. Transgenic expression of the neurotrophin nerve growth factor (NGF) was achieved using injections of Ad.RSVNGF. On histological examination mononuclear inflammatory infiltrate and gliosis were revealed surrounding the injection sites of spinal cords receiving adenovirus but not vehicle. To assess spinal cord function during viral gene expression, animals previously trained in an operant runway task were tested at 7 days postinjection (the peak of viral gene expression) and demonstrated no changes in spinal cord function.

Conclusions. Results of this study using adenoviral neurotrophic gene transfer indicate that it provided an effective tool for the delivery of potentially therapeutic proteins to the injured or diseased spinal cord.

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Anterior cervical discectomy: is fusion necessary?

Gregory C. Dowd and Fremont P. Wirth

Object. A prospective, randomized trial was performed to compare the efficacy of anterior cervical discectomy (ACD) with ACD and fusion (ACDF) for the treatment of cervical spondylosis in patients with neurological compromise.

Methods. Forty-four patients underwent ACD and 40 underwent ACDF. Operative time and length of hospital stay were shorter and there was less need for analgesia in the ACD group. It was found that whereas the incidence of fusion was greater in the ACDF group compared to the ACD group (97 compared with 70%, respectively; p < 0.01), patient satisfaction and a return to preoperative activity level was similar between groups.

Conclusions. Analysis of the results suggests that the addition of a fusion procedure may be unnecessary.

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Anterior cervical plating for the treatment of neoplasms in the cervical vertebrae

Wolfhard Caspar, Tobias Pitzen, Luca Papavero, Fred H. Geisler, and Todd A. Johnson

Object. To assess clinical outcome and survival in patients with cervical vertebral spinal neoplasms after they have undergone anterior decompression and cervical plate stabilization (ACPS) by using either autologous bone graft or polymethylmethacrylate (PMMA) as the anterior load-bearing support structure.

Methods. This was a retrospective case study composed of 30 patients harboring cervical spinal vertebral neoplasms who underwent anterior cervical decompression and (ACPS) within a 7-year period. Postoperative immobilization included treatment in a halo brace in two cases and in a hard cervical collar for the remaining patients. Postoperatively most patients underwent radio- and/or chemotherapy. All patients except one benefited from a significantly improved quality of life with decreased pain and/or improved neurological status. The mean Kaplan—Meier survivoral estimate was 35.8 months (range 8 days–11.3 years, with 10 patients alive at most recent follow-up contact). Patients achieved long-term or lifelong mechanical stability in the cervical spine, and only one patient required a repeated posterior stabilization procedure. No hardware-related complications occurred. One patient died 8 days postoperatively of pneumonia. A nonsignificant difference in survival (p = 0.2164) was observed between patients harboring metastatic neoplasms (26.8 months) and those harboring lymphomatous and multiple myeloma neoplasms (54 months).

Conclusions. Favorable clinical outcome of both neurological symptoms and pain can be achieved using ACPS after surgery for neoplasms in the cervical vertebrae. Furthermore, long-term or lifelong cervical spine mechanical stability with bone fusion is achieved using this technique even when radiation therapy is delivered to the site of the bone graft.

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A biomechanical evaluation of occipitocervical instrumentation: screw compared with wire fixation

R. John Hurlbert, Neil R. Crawford, Won Gyu Choi, and Curtis A. Dickman

Object. The purpose of this study was to compare cable techniques used in occipitocervical fixation with two types of screw fixation. The authors hypothesized that screw fixation would provide superior immobilization compared with cable methods.

Methods. Ten cadaveric specimens were prepared for biomechanical analyses by using standard techniques. Angular and linear displacement data were recorded from the occiput to C-6 with infrared optical sensors after conditioning runs. Specimens underwent retesting after fatiguing. Six methods of fixation were analyzed: Steinmann pin with and without C-1 incorporation; Cotrel-Dubousett horseshoe with and without C-1 incorporation; Mayfield loop with C1–2 transarticular screw fixation; and a custom-designed occipitocervical transarticular screw-plate system. Sublaminar techniques were extended to include C-3 in the fusion construct, whereas transarticular techniques incorporated the occiput, C-1, and C-2 only.

All methods of fixation provided significant immobilization in all specimens compared with the nonconstrained destabilized state. Despite incorporation of an additional vertebral segment, sublaminar techniques performed worse as a function of applied load than screw fixation techniques. Following fatiguing, these differences were more pronounced. The sublaminar techniques failed most prominently in flexion—extension and in axial rotation. On gross inspection, increased angular displacement associated with loosening of the sublaminar cables was observed.

Conclusion. Occipitocervical fixation can be performed using a variety of techniques; all bestow significant immobilization compared with the destabilized spine. All methods tested in this study were susceptible to fatigue and loss of reduction and were weakest in resisting vertical settling. Screw fixation of the occiput—C2 reduces the number of vertebral segments that are necessary to incorporate into the fusion construct while providing superior immobilization and resistance to fatigue and vertical settling compared with sublaminar methods.

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Cervical cord compression caused by a pillow in a postlaminectomy patient undergoing magnetic resonance imaging

Case report

Fumio Suzuki, Masayuki Nakajima, and Masayuki Matsuda

✓ A 66-year-old man, who had undergone osteoplastic laminectomy for posttraumatic cervical myelopathy, underwent a second operation in which the replaced laminae were removed because of postoperative deep wound infection. Follow-up dynamic magnetic resonance imaging with flexion and extension views of the neck 1 year postsurgery demonstrated that the cervical cord was markedly compressed from behind in the extended position, although a wide subarachnoid space was observed in this region when the neck was in the flexed position. The cause of cord compression was the pillow that was placed underneath the patient's neck for maintaining the extended position, not the neck extension itself. This finding indicates that care must be taken during neuroradiological examination not to place a pillow under the neck of a patient who has undergone laminectomy. Nuchal compression could lead to cervical cord injury after laminectomy. Laminoplasty benefits the patient by protecting the cervical cord from secondary injury.

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Cervical corpectomy: report of 185 cases and review of the literature

Mohammed A. Eleraky, Carlos Llanos, and Volker K. H. Sonntag

Object. This study was conducted to determine the indications, safety, efficacy, and complication rate associated with performing corpectomy to achieve anterior decompression of neural elements or for removing anterior lesions.

Methods. Between 1987 and 1998, 185 patients underwent cervical corpectomy for the treatment of degenerative spondylitic disease (81 cases), ossification of posterior longitudinal ligament (16 cases), correction of postoperative kyphosis (31 cases), trauma (39 cases), tumor (10 cases), and infection (eight cases). Ninety-nine patients presented with myelopathy, 48 with radiculomyelopathy, 24 with radicular pain, and 14 with neck muscle pain. Eighty-seven patients underwent a one-level corpectomy; 45 of these patients underwent a discectomy at a different level. Seventy patients underwent a two-level corpectomy; 27 of these patients underwent a discectomy at a different level. Twenty-eight patients underwent a three-level corpectomy. Autograft (iliac crest) was used in 141 cases and allograft (fibula) in 44 cases. All but six patients underwent fixation with an anterior plate-screw system. There were no operative deaths. During the procedure the vertebral artery was injured in four patients and preserved in two of them. No neurological sequelae were encountered. Postoperative hoarseness, transient dysphagia, and pain at the graft site were transitory and successfully managed. The fusion rate was 98.8%. Six patients experienced transient deterioration after surgery but they improved. No patient experienced permanent neurological deterioration and 160 (86.5%) improved.

Conclusions. Corpectomy has an important role in the management of various degenerative, traumatic, neoplastic, or infectious disorders of cervical spine. Following treatment in this series, radiculopathy always improved and myelopathy was reversed in most patients.

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Chondrosarcoma of the spine: 1954 to 1997

Julie E. York, Rasim H. Berk, Gregory N. Fuller, Jasti S. Rao, Dima Abi-Said, David M. Wildrick, and Ziya L. Gokaslan

Object. Primary chondrosarcoma of the spine is extremely rare. During the last 43 years only 21 patients with this disease were registered at The University of Texas M. D. Anderson Cancer Center. The purpose of this study was to examine the demographic characteristics, treatments, and outcomes of this set of patients.

Methods. Medical records for 21 patients were reviewed. Age, sex, race, clinical presentation, tumor histology, tumor location in the spinal column, treatments, surgical details, and response to treatment were recorded. Surgical procedures were categorized as either gross-total resection or subtotal excision of tumor. Neurological function was assessed using Frankel's functional classification. Time to recurrence and survival analyses were performed using the Kaplan—Meier method. The median age of patients was 51 years, with fairly equal gender representation. Eighteen patients underwent at least one surgical procedure for a total of 28 surgical procedures: seven radical resections and 21 subtotal excisions. Radiation therapy was used in conjunction with 10 of the 28 surgical procedures. The median Kaplan—Meier estimate of overall survival for the entire group was 6 years (range 6 months–17 years). Tumors recurred after 18 of the 28 procedures. Kaplan—Meier analysis revealed a statistically significant difference in the per-procedure disease-free interval after gross-total resection relative to subtotal excision (exact log rank 3.39; p = 0.04). The addition of radiation therapy prolonged the median disease-free interval from 16 to 44 months, although this was not statistically significant (exact log rank 2.63; p = 0.16).

Conclusions. Our results suggest that gross-total resection of the chondrosarcoma provides the best chance for prolonging the disease-free interval in patients. Subtotal excision should be avoided whenever possible. Addition of radiation therapy does not appear to lengthen significantly the disease-free interval in this patient population.

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Complex cervical spine neoplastic disease: reconstruction after surgery by using a vascularized fibular strut graft

Case report

Neill M. Wright, Bruce A. Kaufman, Bruce H. Haughey, and Carl Lauryssen

✓ The authors report a case of an aggressive chordoma in the cervical spine of a 15-year-old girl who underwent radical resection followed by reconstruction using an anterior vascularized fibular strut graft and posterior arthrodesis prior to receiving immediate postoperative radiation therapy. The patient had successful graft incorporation 4 months postoperatively. The authors review the advantages of using vascularized fibular strut grafts for the treatment of multilevel cervical spine neoplastic disease and discuss the theoretical advantages of using vascularized grafts that tolerate therapeutic levels of radiation.

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Convective delivery of macromolecules into the naive and traumatized spinal cords of rats

J. David Wood, Russell R. Lonser, Nitin Gogate, Paul F. Morrison, and Edward H. Oldfield

Object. Many macromolecules have the potential to enhance recovery after injury and other lesions of the spinal cord, but because of the limited penetration of these compounds across the blood—spinal cord barrier, they cannot be used effectively. To determine if convective delivery could be used in a common animal model to investigate potential therapeutic macromolecules and to examine the effects of trauma on convective delivery in that model, the authors examined the distribution of a macromolecule in naive and traumatized rat spinal cords.

Methods. Using convection, various infusion volumes ([Vi]; 1, 2, and 4 µl) of 14C-albumin were infused into the dorsal columns of 13 naive and five traumatized rat spinal cords. Volume of distribution (Vd), homogeneity, percentage of recovery, and anatomical location were determined using quantitative autoradiography, scintillation analysis, calculation of kurtosis (K) value, and histological analysis. In the nontraumatized group, Vd was linearly proportional (R2 = 0.98) to Vi (Vd/Vi, 4.3 ± 0.6; mean ± standard deviation), with increases in Vd resulting from linear expansion (R2 = 0.94) primarily in the craniocaudal dimension. In the traumatized spinal cords, the Vd/Vi ratio (3.7 ± 0.5) was smaller (p < 0.02) and distributions were less confined to the craniocaudal dimension, with significantly larger cross-sectional distributions in the region of injury (p < 0.02) compared to the noninjured spinal cords. Histological analysis revealed that after infusion into the dorsal columns, albumin distribution in naive cords was limited to the dorsal white matter, but in the traumatized cords there was penetration into the central gray matter. The distribution of the infusate was homogeneous in the nontraumatized (K = −1.1) and traumatized (K = −1.1) spinal cords. Recovery of radioactivity was not significantly different (p > 0.05) between the nontraumatized (84.8 ± 6.8%) and traumatized (79.7 ± 12.1%) groups.

Conclusions. Direct convective delivery of infusate can be used to distribute macromolecules in a predictable, homogeneous manner over significant volumes of naive and traumatized rat spinal cord. These characteristics make it a valuable tool to investigate the therapeutic potential of various compounds for the treatment of injury and spinal cord disease.

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Development of postoperative fibromatosis after resection of an intraspinal meningioma

Case report

James J. Lynch, Javad Parvizi, Bernd W. Scheithauer, and William E. Krauss

✓ The authors report the case of an adult female patient who developed a paraspinous thoracic fibromatosis (desmoid tumor) after undergoing resection of an intraspinal thoracic meningioma that was complicated by postoperative wound infection. To the best of the authors' knowledge, this is the first report of such a tumor occurring after resection of a spinal meningioma. Awareness of the development of postoperative fibromatosis and recognition of its association with wound sepsis is important. Although rare, this distinctive lesion should be considered in the differential diagnosis of the apparent rapid regrowth of otherwise indolent lesions including meningioma.