Contemporary management of adult intramedullary spinal tumors-pathology and neurological outcomes related to surgical resection.

STUDY DESIGN: Retrospective chart review and review of the recent literature. OBJECTIVES: To present our experience, over an 8-year period, with aggressive microsurgical resection of intramedullary spinal tumors in adults focusing on histology, microsurgical techniques, short-term neurological outcomes, complication avoidance and dorsal column dysfunction (DCD). SETTING: University of Miami/Jackson Memorial Medical Center Miami, FL, USA. METHODS: We conducted a retrospective review of a series of adult patients with intramedullary spinal tumors treated with microsurgical excision at the University of Miami/Jackson Memorial Medical Center between January 1997 and September 2005. RESULTS: Histologic analysis revealed a predominance of ependymomas (50%) with astrocytomas only comprising 12.5% of the tumors. We found no significant difference in pre- and postoperative McCormick grades. Although patients did not manifest significant motor weakness postoperatively as a result of surgery, 43.6% of patients exhibited the signs and symptoms of DCD, resulting in significant postoperative morbidity. CONCLUSION: We present a contemporary adult series of intramedullary spinal tumors. The most significant postoperative morbidity experienced by patients was DCD. The neurosurgeon should recognize the impact of these symptoms, prepare the patient and his/her family for the possibility of DCD, and minimize dorsal column manipulation in an attempt to decrease its prevalence.

High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Although Bracken et al have demonstrated a significant neuroprotective effect of high-dose intravenous (i.v.) methylprednisolone (MP) within 8 h post spinal cord injury (SCI), this practice has recently been challenged. We hypothesized it is possible that acute corticosteroid myopathy (ACM) may occur secondary to the MP. This pilot study was performed to test this hypothesis. SETTING: University of Miami School of Medicine/Jackson Memorial Hospital, Miami VA Medical Center, FL, USA. METHODS: Subjects included five nonpenetrating traumatic SCI patients, who received 24 h MP according to National Acute Spinal Cord Injury Studies (NASCIS) protocol, and three traumatic patients who suffered SCI and did not receive MP. Muscle biopsies and electromyography (EMG) were performed to determine if myopathic changes existed in these patients. RESULTS: Muscle biopsies from the SCI patients who received 24 h of MP showed muscle damage consistent with ACM in four out of five cases. EMG studies demonstrated myopathic changes in the MP-treated patients. In the three patients who had SCI but did not receive MP, muscle biopsies were normal and EMGs did not reveal evidence of myopathy. CONCLUSION: Our data suggest that MP in the dose recommended by the NASCIS may cause ACM. If this is true, part of the improvement of neurological recovery showed in NASCIS may be only a recording of the natural recovery of ACM, instead of any protection that MP offers to the injured spinal cord.

Surgery for lumbar disc herniation during pregnancy.

STUDY DESIGN: The case reports of three pregnant patients with lumbar disc herniation causing cauda equina syndrome or severe neurologic deficits are presented to illustrate that disc surgery during gestation is a safe method of management. OBJECTIVE: To emphasize the importance of recognizing and definitively treating lumbar disc displacement causing neurologic deficits during pregnancy. SUMMARY OF BACKGROUND DATA: The advent of magnetic resonance imaging and modern surgical techniques for treatment of lumbar disc displacement allows safe management of this condition at any stage of gestation. A review of the literature on the risks of nonobstetric surgery and the risks of delaying disc surgery until delivery shows that operating at any stage during gestation for severe neurologic deficit secondary to lumbar disc displacement is justified. METHODS: A review of the literature on the use of magnetic resonance imaging scan and nonobstetric surgery during pregnancy was performed. Three case reports of the authors' patients who had lumbar disc displacement with cauda equina syndrome or severe neurologic deficit are presented. Patients were placed prone on a four-poster frame, and an epidural anesthetic agent was administered. A one-level hemilaminectomy, partial facetectomy, and disc excision were performed in all three cases. RESULTS: The methods used for diagnosis and surgical treatment of three patients with disc herniation during pregnancy resulted in a satisfactory outcome for both mother and child. The medical literature supports surgical intervention in pregnant patients with cauda equina syndrome and severe and/or progressive neurologic deficit(s) from lumbar disc displacement at any state of gestation. CONCLUSION: Although extremely rare, cauda equina syndrome and severe and/or progressive neurologic deficit caused by lumbar disc displacement can occur during pregnancy. The prevalence of symptomatic lumbar disc herniation during pregnancy may be on the increase because of the increasing age of patients who are becoming pregnant. These cases showed, and the literature confirms, that pregnancy at any stage is no contraindication to magnetic resonance imaging scan, epidural and/or general anesthesia, and surgical disc excision.

Computer-assisted fluoroscopic targeting system for pedicle screw insertion.

OBJECTIVE: Biplanar fluoroscopic imaging linked to a computer-driven mechanical end-effector is under development as a targeting system for spinal surgery. This technology has the potential to enhance standard intraoperative fluoroscopic information for localization of the pedicle entry point and trajectory, and it may be an effective alternative to the computed tomography-based image-guided system (IGS) in pedicle screw placement. A preclinical study to assess the accuracy and time efficiency of this system versus a conventional IGS was conducted. METHODS: Pedicle screw placement was performed in six cadavers from T1 to S1 levels using the ViewPoint IGS (Picker International, Inc., Cleveland, OH) on one side versus the Fluorotactic guidance system (Z-Kat, Inc., Miami, FL) on the other side. Of 216 possible pedicles, 208 were instrumented; 8 pedicle diameters were too small or were not adequately imaged. Postinsertion, each pedicle was assessed for the presence and location of cortical perforation using computed tomographic scanning and direct visualization. RESULTS: The number of successful screw placements was 89 (87.3%) of 102 for IGS and 87 (82.1 %) of 106 for the Fluorotactic guidance system, respectively. The mean time to register and operate on one level using the Fluorotactic guidance system was 14:34 minutes (minutes:seconds), compared with 6:50 minutes using the IGS. The average fluoroscope time was 4.6 seconds per pedicle. CONCLUSION: Our data indicate that this first-generation fluoroscopy-based targeting system can significantly assist the surgeon in pedicle screw placement. The overall accuracy is comparable to an IGS, especially in the region of T9-L5. A second-generation system with a faster end-effector and user-friendly interface should significantly reduce the operating and fluoroscope time.

Tuberculosis of the axis in a patient with systemic sarcoidosis: technique of posterior open biopsy of the dens: case report.

OBJECTIVE AND IMPORTANCE: This case report illustrates the importance of obtaining tissue from a destructive lesion of the dens in a patient with systemic sarcoidosis. Although sarcoidosis can involve the axial skeleton, tissue obtained at the time of C1-C2 fusion demonstrated unsuspected pathological features, which dramatically altered the subsequent medical treatment. The technique of open posterior biopsy of the dens is illustrated, and the advantages of the approach are discussed. CLINICAL PRESENTATION: A 40-year-old woman with systemic sarcoidosis developed neck pain and atlantoaxial instability. Imaging revealed multiple thoracic and cervical vertebral abnormalities, including a destructive enhancing lesion involving the base of the dens. INTERVENTION: At the time of posterior C1-C2 fusion, we elected to perform an open biopsy of the base of the dens. A 16-gauge biopsy needle was introduced along the medial portion of the left C2 pars, aiming medially toward the base of the odontoid process. This procedure was performed under direct observation, with fluoroscopic guidance. The biopsy specimen contained caseating granulomas, and cultures were positive for Mycobacterium tuberculosis. CONCLUSION: The unusual presentation, the technique, and the importance of obtaining tissue to confirm the diagnosis of tuberculous involvement of the dens are emphasized. The relationship between sarcoidosis and tuberculosis reported in the literature is reviewed. In the current case, cell wall-positive tuberculous bacteria were cultured, confirming the presence of two separate diseases in the same patient.

Treatment of a retroperitoneal lymphocele after lumbar fusion surgery with intralesional povidone iodine: technical case report.

OBJECTIVE AND IMPORTANCE: This case report illustrates an uncommon complication from the retroperitoneal exposure of the lumbar spine. The diagnosis and management of a retroperitoneal lymphocele is presented. The lymphocele was treated with intralesional povidone iodine (Betadine; Purdue-Frederick, Norwalk, CT), which eradicated the lesion and provided symptomatic relief to the patient. CLINICAL PRESENTATION: A young woman developed an iatrogenic, rapidly progressive spondylolisthesis after having undergone three previous lumbar surgeries for radiculopathy at the L5-S1 level. INTERVENTION: A back-front-back approach was used for operative reduction and fusion of the spondylolisthesis. The patient's postoperative course was complicated by a retroperitoneal lymphocele. She presented with symptoms of urinary urgency and incontinence. The lymphocele was successfully treated with repeated drainage and sclerosis with povidone iodine. The patient ultimately developed a solid fusion, and her pain resolved. CONCLUSION: A retroperitoneal lymphocele is an uncommon complication caused by the surgical exposure of the lumbar spine when a ventral approach is used. In this case, it was diagnosed and treated without further surgical intervention.

Assessment of the malignant potential of mitogen stimulated human Schwann cells.

Human Schwann cells (SCs) can be isolated and expanded with mitogens using cell culture techniques. These cells have been demonstrated to promote axonal regrowth in both the central and peripheral nervous system. Primary rat SCs can be immortalized with long-term exposure to mitogens. Transplantation of these cells into an autogenic host sciatic nerve results in the formation of tumors. Human cells are, in general, relatively more resistant to malignant transformation, but any potential risk for inducing tumor after transplantation of SCs in humans must be excluded. In this study, the malignant potential of mitogen expanded human SCs injected into the sciatic nerve of immunodeficient mice was investigated. Human SCs were isolated from human peripheral nerves and placed in cell culture, expanded with mitogens (heregulin and forskolin) for many passages (0-6 times), and then injected within the sciatic nerve of Severe Combined Immunodeficient (SCID) rat or mice. As a positive control for tumor formation in this xenograft model, human glioma cells were also injected. The proliferation index (PI) of the human SCs gradually decreased with each passage in cell culture. SC purity remained stable until the 6th passage, and then decreased significantly for older passages, so that the cultures were over-grown with fibroblasts. The incidence for rat or human glioma cells to induce tumors was 100% and 92%, respectively. In contrast, there was no tumor induced by human primary or mitogen expanded SCs. Demyelination, remyelination and formation of connective sheath at the injection site were observed in some cases after injection of the human SCs. Thus, mitogen-expanded human SCs do not produce tumors when transplanted in vivo, which suggests that these cells are safe, and deserve further study towards their use in clinical transplantation.

Apoptosis after traumatic human spinal cord injury.

OBJECT: Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. METHODS: The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. CONCLUSIONS: These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.

Cold preserved nerve allografts: changes in basement membrane, viability, immunogenicity, and regeneration.

Rat sciatic nerve graft segments were harvested and pretreated by either placement in the University of Wisconsin Cold Storage Solution at 5 degrees C and storage from 1 to 26 weeks, or repeatedly freezing (-40 degrees C) and thawing (20 degrees C). Following pretreatment, grafts were transplanted as either syngeneic or allogeneic nerve grafts. Storage and freeze-thawing did not affect the Schwann cell basal lamina or laminin distribution of the peripheral nerve. Graft cell viability decreased with increasing time of storage, with some viable cells detectable even after 3 weeks of storage. Freeze-thawed grafts were not viable. Increasing time of storage led to decreasing immune response and graft rejection, but improved regeneration. Freeze-thawed and 26-week stored allografts were nonimmunogenic and rejection was not seen, but regeneration was delayed compared to autografts. Graft storage may become a useful adjunct to clinical nerve allografting to permit elective scheduling of surgery, provide greater time for preoperative tissue testing, and possibly blunt the immune response.

The radiographic and imaging characteristics of porous tantalum implants within the human cervical spine.

STUDY DESIGN: Seven cadaveric cervical spines were implanted with a porous tantalum spacer and a titanium alloy spacer, and their radiographic and imaging characteristics were evaluated. OBJECTIVE: To determine the radiographic characteristics of porous tantalum and titanium implants used as spacers in the cervical spine. SUMMARY OF BACKGROUND DATA: Anterior decompressive surgery of the disc space or the vertebral body creates a defect that frequently is repaired with autologous bone grafts to promote spinal fusion. Donor site morbidity, insufficient donor material, and additional surgical time have spurred the development of biomaterials to replace or supplement existing spinal reconstruction techniques. Although the promotion of a solid bony fusion is critical, the implanted biomaterial should be compatible with modern imaging techniques, should allow visualization of the spinal canal and neural foramina, and should permit radiographic assessment of bony ingrowth. METHODS: Cadaveric spines containing the implants were imaged with plain radiography, computerized tomography, and magnetic resonance imaging. The image distortion produced by the implants was determined qualitatively and quantitatively. RESULTS: The tantalum and titanium spacers were opaque on plain radiographic films. On computed tomographic scans, more streak artifact was associated with the tantalum implants than with the titanium. On magnetic resonance imaging, the porous tantalum implant demonstrated less artifact than did the titanium spacer on T1- and T2-weighted spin echo and on T2*-weighted gradient-echo magnetic resonance images. Overall, the tantalum implant produced less artifact on magnetic resonance imaging than did the titanium spacer and therefore allowed for better visualization of the surrounding bony and neural structures. CONCLUSION: The material properties of titanium and porous tantalum cervical interbody implants contribute to their differential appearance in different imaging methods. The titanium implant appears to image best with computed tomography, whereas the porous tantalum implant produces less artifact than does the titanium implant on several magnetic resonance imaging sequences.

Management of posttraumatic syringomyelia using an expansile duraplasty. A case report.

STUDY DESIGN: A patient in whom posttraumatic syringomyelia developed 34 years after an L2 fracture is reported. OBJECTIVES: To review the pathophysiology and current management modalities for posttraumatic syringomyelia. The delayed presentation and management rationale of this case are emphasized. SUMMARY OF BACKGROUND DATA: This case represents the most delayed onset of symptoms from a posttraumatic syrinx reported in the literature. Although lysis of arachnoid adhesions and expansile duraplasty to recreate the subarachnoid space have been described for nonshuntable syrinxes, this form of management was used as the primary management modality in this case. METHODS: A posttraumatic syrinx was managed by lysis of the arachnoid adhesions, fenestration of the cyst, and an expansile duraplasty. RESULTS: After surgery, the patient's symptoms improved, and magnetic resonance imaging showed a decrease in the size of the syrinx. CONCLUSION: Posttraumatic syringomyelia represents one of the few surgically remediable presentations of spinal cord injury. Consequently, it is necessary to continuously develop and monitor new management options for this disease. In the case reported here, the syrinx was treated successfully without the implanting a drainage tube.

Management of postoperative infections after spinal instrumentation.

The authors retrospectively reviewed 452 consecutively treated patients who underwent a spinal instrumentation procedure at a single institution to establish which patients and which surgical approaches might be associated with an increased risk of developing deep wound infections and to determine the efficacy with which the institution's current treatment strategy eradicates these infections. Wound infections occurred in 17 patients (10 men and seven women) with spinal instrumentation (incidence 3.8%). All infections occurred after posterior spinal instrumentation procedures (7.2%); there were no infections after anterior instrumentation procedures regardless of the level. Each patient was assigned an infection risk factor (RF) score depending on the number of RFs identified in an individual patient preoperatively. The mean RF score of patients who developed infections was 2.18, whereas the mean RF score for a procedure-matched, infection-free control group was 0.71. The mean number of days from surgery to clinical presentation was 27.6 days (range 4-120 days), and the mean increase in hospitalization time for the subset of patients who developed infections was 16.6 days. The most common organism isolated from wound cultures was Staphylococcus aureus (nine of 17 cases). Of the 17 patients, five had infections involving multiple organisms. All patients were infection free at a minimum of 8 months follow-up review. The current treatment regimen advocated at this institution consists of operative debridement of the infected wound, a course of intravenous followed by oral antibiotic medications, insertion of an antibiotic-containing irrigation-suction system for a mean of 5 days, and maintenance of the instrumentation system within the infected wound.

The influence of heregulins on human Schwann cell proliferation.

The use of Schwann cell (SC) autotransplantation to influence neural repair in humans is dependent upon identifying mitogens that will effectively expand human Schwann cells (SCs) in culture. The recent purification and molecular cloning of glial growth factor (GGF), a potent mitogen for rat Schwann cells, has led to the recognition that a family of proteins (GGF/HRG/NDF/ARIA) are alternatively spliced products of a single gene. The heregulins (HRGs) have been characterized with respect to their influence on human breast cancer cell lines; here we examined whether the HRGs have mitogenic activity for human SCs. Using DNA synthesis assays and serial passaging of cells in culture, we demonstrate that HRG is an effective mitogen for human SCs and that, in the presence of agents that elevate cAMP, it is possible to expand these cells over multiple passages without overwhelming fibroblast contamination. One putative target for this family of proteins is p185erbB2, and EGF-like receptor tyrosine kinase that is encoded by the erbB2 protooncogene. In this report we also demonstrate that the erbB2/3/4 messages as well as the erbB2/3 receptor proteins are present within cultured human SCs. The addition of HRG to human SCs results in tyrosine phosphorylation of a 185 kDa protein. In the presence of stimulatory concentrations of HRG, a blocking monoclonal antibody (2C4) to p185erbB2 is capable of significantly inhibiting phosphorylation of a 185 kDa protein as well as the subsequent incorporation of 3H-thymidine within the human SC. These latter results implicate an important role for p185erbB2 in mediating the mitogenic response of human SCs to HRGs.

Axon-induced mitogenesis of human Schwann cells involves heregulin and p185erbB2.

The ability of sensory axons to stimulate Schwann cell proliferation by contact was established in the 1970s. Although the mitogen responsible for this proliferation has been localized to the axon surface and biochemically characterized, it has yet to be identified. Recently a family of proteins known as heregulins (HRGs) has been isolated, characterized, and shown to interact with a number of class 1 receptor tyrosine kinases, including the erbB2, erbB3, and erbB4 gene products. These factors include glial growth factor, a Schwann cell mitogen. We have tested the effects of antibodies against components of this system (HRG beta 1 and p185erbB2) in cocultures of rat sensory neurons and human (or rat) Schwann cells to elucidate the role of these proteins in axon-induced Schwann cell proliferation. 2C4, a monoclonal antibody specific for the human p185erbB2 receptor tyrosine kinase, bound to the surface of human Schwann cells and reduced human Schwann cell incorporation of [3H]thymidine by > 90% compared with untreated controls in this coculture system. This antibody had no effect on rat Schwann cell incorporation of [3H]thymidine under similar conditions. A polyclonal antibody raised against HRG beta 1 reduced human and rat Schwann cell incorporation of [3H]thymidine by nearly 80% and up to 49%, respectively, relative to controls. These results imply that a HRG, or a HRG-like molecule, is a component of the axonal mitogen. This mitogen is presented to Schwann cells by axons and induces proliferation through an interaction that involves p185erbB2 on Schwann cells.

Clival chordoma presenting with acute brain stem hemorrhage.

The authors present a case of a 29-year-old man who developed rapidly progressive cranial nerve palsies and a right hemiparesis secondary to a pontine hemorrhage. The rare but correct diagnosis of a clival chordoma which had invaded the brain stem and subsequently hemorrhaged was based on computed tomography and magnetic resonance imaging. The diagnosis was confirmed at surgery when the patient underwent a successful operative decompression of tumor and clot from the pons via a sub-occipital craniotomy. This represents the first case of a clival chordoma to hemorrhage into the brain stem, which was diagnosed preoperatively and the patient survived.

Venous thromboembolism after brain tumor surgery: a retrospective review.

We retrospectively reviewed the incidence rate of clinical postoperative deep vein thrombosis and/or pulmonary embolism in 1703 patients undergoing initial craniotomy for meningioma, glioma, or cerebral metastasis. The incidence rate of clinical thromboembolic complications was 1.59% for all tumor groups within the first 4 weeks of surgery. Patients undergoing surgery for meningiomas had a statistically significant increased risk of thromboembolism despite fewer overall perioperative risk factors, when compared with the other tumor groups. The tumor-specific incidence rates of deep vein thrombosis and/or pulmonary embolism for meningioma, glioma, and metastasis were 3.09%, 0.97%, and 1.03%, respectively. Whether this difference was a result of increased surgical time or an inherent property of meningiomas could not be ascertained.

Spinal hemangioblastoma, syrinx, and hydrocephalus in a two-year-old child.

A two-year-old child presented with an acute inability to bear weight. Radiological investigation revealed a large cervicothoracolumbar syrinx of no known cause. During investigation, acute communicating hydrocephalus developed, which required a shunt. At surgery, a small thoracic spinal cord hemangioblastoma was discovered and excised. Complete recovery with collapse of the syrinx followed. The clinical features of this rare childhood tumor and its associated effects are discussed.