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Object. The authors compared the incidence of radiologically documented changes and symptomatic adjacent-level cervical disc disease after single-level discectomy and subsequent cervical fusion or arthroplasty in two independent prospective clinical studies. Methods. The patients were treated with the Affinity Anterior Cervical Cage System or the Bryan Artificial Cervical Disc. In each study the patients were required to undergo serial cervical radiography preoperatively and 24 months postoperatively, as well as serial clinical evaluations including documentation of adverse events, neurological status, and results of the 36-item Short Form Health Survey. All serial radiographs were reviewed prior to evaluating the clinical symptoms for development of increasing or new adjacent degenerative disc disease (DDD). Subsequently, the clinical data were analyzed. For various reasons of exclusion, the cases analyzed in the Bryan disc—treated cohort consisted of 74 patients and in the Affinity system—treated cohort there were 158 patients. New anterior osteophyte formation or enlargement, increased narrowing of an interspace, new DDD, and calcification of the anterior longitudinal ligament were the radiological findings indicative of adjacent-level disease. Fusion was associated with a significant increase in x-ray film—based changes of adjacent-disc disease (p = 0.009, odds ratio [OR] 2.44). In the cage fusion series, the incidence of symptomatic adjacent-level DDD was statistically greater than that in the group treated with the artificial disc (p = 0.018), and the patients required a statistically greater number of medical treatments related to episodic symptoms of neck, shoulder, and arm pain attributed to new disc disease (p = 0.001, OR 35.8). Conclusions. In comparing these prospective studies the authors demonstrated that maintaining motion rather than fusion will prevent symptomatic adjacent-disc disease and will decrease adjacent-level radiological indicators of disease at a 24-month postoperative interval.

Study design A clinical prospective observational cohort study of 15 patients undergoing cervical intervertebral disc replacement. Objective To assess the safety, clinical stability, and capacity of a newly designed cervical intervertebral disc replacement for preserving motion in the cervical spine of patients with degenerative disc disease. Summary of background data Anterior cervical discectomy and interbody fusion results in loss of motion segments and there is evidence of accelerated degenerative changes occurring at adjacent levels. Intervertebral disc replacement may be a valid alternative to fusion. There is a need for cervical disc replacement to be evaluated in prospective studies before it can be adopted as an acceptable surgical technique. Methods The study enrolled 15 patients with cervical radiculopathy or myelopathy and radiologically confirmed cervical disc herniation or posterior vertebral body osteophytes. Eligibility for the study required that patients have either a previous adjacent-level surgical or congenital spinal fusion or radiologic evidence of adjacent-level degenerative disc disease. After decompressive surgery via an anterior approach, all 15 patients received the artificial joint. Follow-up visits were at set intervals and included clinical examination, radiologic assessment, and evaluation by patient-completed questionnaires. Results In all cases, the artificial joint maintained motion at the operative levels while reestablishing intervertebral height. The procedure was considered safe for experienced spine surgeons to perform, and the device was stable, with no dislocation of components or backing out of screws. Two screws broke, but without any consequence. Improvements in assessment scores were noted. Conclusions Cervical intervertebral motion can be maintained with the new device, which is clinically stable. Meticulous attention must be paid to the surgical technique to maximize the chances of a good result. The pilot study was successful, although it has yet to be determined what conditions will benefit most from this technology.

OBJECTIVE The objective of the Brain Tumor Cooperative Group NIH Trial 87-01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas.METHODS The study involved a randomized comparison of surgery, extern

Object. The authors report the preservation of motion at surgically treated and adjacent spinal segments after placing an artificial cervical joint (ACJ) and they describe the influence of interbody fusion on changes in angulation occurring in the sagittal plane at adjacent levels in the treatment of cervical spondylosis. Methods. The authors conducted a prospective nonrandomized study of patients in whom an ACJ was placed or autologous bone graft interbody fusion was performed. Angular measurements at levels adjacent to that surgically treated were calculated using plain flexion—extension radiographs obtained at 6-month intervals. Analyses of qualitative data, such as increase or decrease in adjacent-level motion, and the degree of disc degeneration were performed. Quantitative data were also analyzed. In the fusion group a significant increase in adjacent-level movement was demonstrated at the 12-month follow-up visit compared with the group of patients in whom ACJs were placed (p < 0.001). The increase in movement occurred predominantly at intervertebral discs that were preoperatively regarded as normal (p < 0.02). An overall reduction in adjacent-level movement was observed in patients who underwent joint replacement, although this was compensated for by the movement provided by the ACJ itself. Conclusions. Fusion results in increased motion at adjacent levels. The increase in adjacent-level motion derives from those discs that appear radiologically normal prior to surgery. It remains unknown whether ACJs have a protective influence on adjacent intervertebral discs.

Mr Chairman, members, and guests of this annual international meeting on stroke, sponsored by the Stroke Council of the American Heart Association, an organization to which I have devoted over 20 years of admiration and service, it is an honor and privilege to present the Willis Lecture for 1998. Sir Charles Willis published the Anatome of the Brain and Nerves over 300 years ago. Feindel edited an excellent compilation of Willis’ work and published his tercentenary edition, entitled Cerebri Anatome, in 1964 . 1 Willis’ publication was more than anatomy of the brain and nerves. It set forth a number of functional as well as anatomic descriptions of the brain and the cranial nerves. The most significant point of the work was the description of the functional anatomy of the cerebral circulation. Willis applied, for the first time, the knowledge of William Harvey’s brilliant discovery to the special problems of the blood supply to the brain. He gave the anatomic description of the arterial circle at the base of the brain. He recognized the significance of this unique vascular anastomosis. He supported his insight into the principle of collateral circulation to the brain by the intravascular injection of colored dyes and by ligation, in animals, of blood vessels supplying and draining the brain. Finally, he attempted to correlate the problems presented in his medical practice in light of these anatomic and experimental results often supported by autopsy observations. Clearly, he recognized that the carotid and vertebral arteries in the neck were the source of the blood supply to the brain and were integral to the cross-circulation described. It is, therefore, highly appropriate that we focus today on the most commonly performed arterial surgical procedure, carotid endarterectomy, and the circuitous road of critique and clinical study it has followed to become …

The adducts of nitric oxide (NO), diethylamine/NO (DEA/NO) and diethylenetriamine/NO (DETA/NO), are new NO donors that spontaneously release NO in aqueous solutions. These donors may have therapeutic advantages over sodium nitroprusside (SNP), which depends on metabolism to yield NO. This study was performed to define and compare the pharmacodynamic properties of these NO donors on isolated rings of human, canine, and porcine basilar arteries and further to compare canine and porcine common carotid arteries precontracted with KCl. The median effective concentration (EC50) and the basic effect of 100 microM were determined for each NO donor. On basilar arteries, DEA/NO was the most potent but the maximal dilatation produced by 100 microM did not persist for 60 min, whereas that of DETA/NO and SNP did. DETA/NO was more potent than SNP on all three species of basilar arteries but was the least potent on peripheral (carotid) arteries. Methylene blue in equimolar concentrations significantly inhibited the vasorelaxant effects of DEA/NO and DETA/NO, suggesting a common mechanism of action. Of the NO donors studied, the pharmacodynamic properties of DETA/NO seemed most relevant clinically as a cerebrovascular dilator in being more potent than SNP while producing sustained vasorelaxation.

Background and Purpose Our aim was to determine the perioperative morbidity and mortality rates of patients in the surgical arm of the multi-institutional, prospective, randomized Asymptomatic Carotid Atherosclerosis Study (ACAS). Methods Of 828 patients with carotid stenosis of 60% or more randomized to the surgical arm of ACAS, 721 underwent carotid endarterectomy (CEA). To qualify for participation, surgeons were required to have performed at least 12 CEAs per year with a combined neurological morbidity and mortality rate no greater than 3% for asymptomatic patients and 5% for symptomatic patients. Clinical centers had to demonstrate arteriographic morbidity less than 1% and mortality less than 0.1% per year. Primary events were stroke and death in the period between randomization and 30 days after surgery; secondary events were transient ischemic attack and myocardial infarction occurring in the same period. Results Of the 721 patients who underwent CEA, 1 died and 10 others had strokes within 30 days (1.5%). Of the 415 who underwent arteriography after randomization but before CEA, 5 (1.2%) suffered transient ischemic attack or stroke caused by arteriography. Thus, a nearly equal risk of stroke was associated with both CEA and carotid arteriography. In addition, 6 transient ischemic attacks and 3 myocardial infarctions could be directly linked to CEA, for a total CEA event rate of 2.6%. Conclusions Patients with asymptomatic internal carotid artery stenosis exceeding 60% reduction in diameter who are acceptable candidates for elective operation may be considered for CEA if the combined arteriographic and surgical complication rates are 3% or less.

Study Design. This study ascertained the effects of discectomy on prostaglandin synthesis. Objectives. The purpose of these novel experiments was to measure the levels of two prostaglandins in lumbar epidural fluid obtained from an area subjected to discectomy. For comparison, lumbar epidural fluid from a site not disturbed by discectomy and fluid from a subcutaneous site were analyzed for the prostaglandins. Summary of Background Data. Previous studies have shown that nuclear material obtained from degenerative discs manifests an extraordinarily high level of phospholipase A 2 activity. Others have hypothesized that the known inflammatory effects of phospholipase A 2 are due to the release of arachidonic acid, which is converted to various eicosanoids, including several algesic prostaglandins (PGI 2 and PGE 2 ). No previous study has continuously measured prostaglandin levels in epidural fluid or assessed the effect of discectomy on prostaglandin production. Methods. An ultrafiltrate of lumbar epidural fluid of dogs was obtained from indwelling catheters located adjacent to spinal areas that were not subjected to discectomy as well as from subcutaneous tissues. The fluid was collected daily for 14 days and analyzed for PGE 2 and 6-keto PGF 1α (the stable metabolite of PGI 2 ) by radioimmunoassay. Results. The concentration of 6-keto PGF 1α and PGE 2 in fluid collected during the first 24 hours was significantly higher in the area of discectomy than in the epidural region that was no subjected to discectomy and significantly higher than in fluid obtained from the subcutaneous site. The high level of these prostaglandins at the discectomy site fell rapidly, so that by the end of 48 hours the differences in values between spinal fluid from the discectomy and nondiscectomy regions were not statistically significant. The concentration of the prostaglandins in epidural fluid decreased with time and became minimal within the second week. Conclusion. The removal of normal discs is accompanied for 24 hours by a marked rise in the synthesis of two prostaglandins known to produce pain. Because the concentration of prostaglandins in epidural fluid decreased rapidly thereafter, the initial surge obtained appears to be associated more with chemical factors such as phospholipase A 2 than with wound healing.

Previous studies describing the use of cryoculture methods have focused on the efficacy of the method for studying neuron attachment and neurite outgrowth on intact sections of nerve, and rodent and even human brain. The cryoculture method has shown promise for determining the presence of cell attachment- and neurite-growth-inhibiting molecules in such specimens, and some studies have also attempted to neutralize such molecules with antibodies to myelin inhibitory proteins, nerve growth factor, or factors present in conditioned media that may counteract the repulsiveness of some of these molecules preserved in sections of, for example, myelinated nerves or adult brain white matter. The present study describes the novel use of lesioned central nervous system cryocultures as substrates for investigating the attachment of embryonic neurons and PC12 cells. In addition to demonstrating the use of this novel scar substrate to extend previous ‘scar-in-a-dish’ models (David et al. (1990) Neuron, 5: 463–469; Rudge and Silver (1990) J. Neurosci., 10: 3594–3603; Rudge et al. (1989) Exp. Neurol., 103: 1–16), the present study also describes antibody and lectin perturbations of putative inhibitory molecules that result in an enhanced attachment of cells to cryosection cultures of brain and spinal cord wounds.

The purpose of this study was to investigate the presence of any correlation between recurrent radicular pain during the first six months following first surgery for herniated lumbar intervertebral disc and the amount of lumbar peridural fibrosis as defined by MR imaging. 197 patients who underwent first-time single-level unilateral discectomy for lumbar disc herniation were evaluated in a randomized, double-blind, controlled multicenter clinical trial. Clinical assessments, performed by physicians blinded to patient treatment status, were conducted preoperatively and at one and six months postoperatively. The enhanced MR images of the operative site utilized in the analysis were obtained at six months postoperatively. Radicular pain was recorded by the patient using a validated visual analog pain scale in which 0 = no pain and 10 = excruciating pain. The data obtained at the 6 month time point were analyzed for an association between amount of peridural scars as measured by MR imaging and clinical failure as defined by the recurrence of radicular pain. The results showed that the probability of recurrent pain increases when scar score increases. Patients having extensive peridural scar were 3.2 times more likely to experience recurrent radicular pain than those patients with less extensive peridural scarring. In conclusion, this prospective, controlled, randomized, blinded, multicenter study has demonstrated that there is a significant association between the presence of extensive peridural scar and the occurrence of recurrent radicular pain.

Purpose: The selection of surgeons to participate in a prospective randomized trial comparing the efficacy of a surgical method with medical management is critically important because it will have a direct impact on the outcome of the study and the future use of the operation. We report the success of the method used for selecting surgeons who participated in the Asymptomatic Carotid Atherosclerosis Study (ACAS) by examining the surgical morbidity and mortality rates and the outcome of the study.Methods: A Surgical Management Committee established criteria for auditing surgeons who wished to participate in the study. The parameters included a minimum performance of at least 12 carotid endarterectomies (CEA) per year and an audit of each surgeon's last 50 consecutive CEAs with required documentation of a combined neurologic morbidity and mortality rate of

Object The long-term function of an artificial cervical disc device is critical to its clinical success. The Prestige I Cervical Disc System has been used clinically since June 1998, and long-term results can now begin to be assessed. The authors conducted clinical and radiographic examinations at 3 and 4 years postoperatively to evaluate the long-term performance of the Prestige I device. Methods A pilot trial was initiated in which the Prestige I disc was implanted in a cohort of patients with end-stage disease, who often had a history of multiple previous fusion procedures. All patients were followed according to a standardized clinical and radiographic protocol until 2 years postoperatively. Outcome measures included the Short Form–36 (SF-36) and Neck Disability Index (NDI) questionnaires, neurological status, and radiographic status. To evaluate the long-term function of the device, Ethics Committee approval was obtained to assess the patients at 3 and 4 years postoperatively. All patients were contacted, and after signing an additional informed consent document, were reevaluated according to the standardized protocol. Of the 17 patients in the original cohort, 13 were evaluated at 3 years and 14 were evaluated at 4 years postoperatively. Clinical outcome measures including the NDI and SF-36 showed good improvement, especially when the end-stage nature of the disease is considered. Radiographic analysis showed that the Prestige I disc maintained motion at the treated segment at 3 and 4 years postoperatively. Conclusions In this report the authors demonstrate the clinical viability of the Prestige I cervical disc system at long-term postoperative intervals, even in the more severe biomechanical environment of end-stage disease.

Background and Purpose Indications for carotid endarterectomy have engendered considerable debate among experts and have resulted in publication of retrospective reviews, natural history studies, audits of community practice, position papers, expert opinion statements, and finally prospective randomized trials. The American Heart Association assembled a group of experts in a multidisciplinary consensus conference to develop this statement. Methods A conference was held July 16-18, 1993, in Park City, Utah, that included recognized experts in neurology, neurosurgery, vascular surgery, and healthcare planning. A program of critical topics was developed, and each expert presented a talk and provided the chairman with a summary statement. From these summary statements a document was developed and edited onsite to achieve consensus before final revision. Results The first section of this document reviews the natural history, methods of patient evaluation, options for medical management, results of surgical management, data from position statements, and results to date of prospective randomized trials for symptomatic and asymptomatic patients with carotid artery disease. The second section divides 96 potential indications for carotid endarterectomy, based on surgical risk, into four categories: (1) Proven: This is the strongest indication for carotid endarterectomy; data are supported by results of prospective contemporary randomized trials. (2) Acceptable but not proven: a good indication for operation; supported by promising but not scientifically certain data. (3) Uncertain: Data are insufficient to define the risk/benefit ratio. (4) Proven inappropriate: Current data are adequate to show that the risk of surgery outweighs any benefit. Conclusions Indications for carotid endarterectomy in symptomatic good-risk patients with a surgeon whose surgical morbidity and mortality rate is less than 6% are as follows. (1) Proven : one or more TIAs in the past 6 months and carotid stenosis ≥ 70% or mild stroke within 6 months and a carotid stenosis ≥ 70%; (2) acceptable but not proven : TIAs within the past 6 months and a stenosis 50% to 69%, progressive stroke and a stenosis ≥ 70%, mild or moderate stroke in the past 6 months and a stenosis 50% to 69%, or carotid endarterectomy ipsilateral to TIAs and a stenosis ≥ 70% combined with required coronary artery bypass grafting; (3) uncertain : TIAs with a stenosis proven inappropriate: moderate stroke with stenosis Proven: none. (As this statement went to press, the National Institute of Neurological Disorders and Stroke issued a clinical advisory stating that the Institute has halted the Asymptomatic Carotid Atherosclerosis Study (ACAS) because of a clear benefit in favor of surgery for patients with carotid stenosis ≥60% as measured by diameter reduction. When the ACAS report is published, this indication will be recategorized as proven. (2) acceptable but not proven : stenosis >75% by linear diameter; (3) uncertain : stenosis >75% in a high-risk patient/surgeon (surgical morbidity and mortality rate >3%), combined carotid/coronary operations, or ulcerative lesions without hemodynamically significant stenosis; (4) proven inappropriate : operations with a combined stroke morbidity and mortality >5%.

Two opioid neuropeptides, methionine enkephalin (ME) and β-endorphin (BE), and one tachykinin neuropeptide, substance P (SP), were quantified in 10 prolactin (PRL)-secreting human pituitary adenomas and in 10 control human pituitaries. Immunohistochemical techniques provided appropriate staining for PRL. Reversed-phase high performance liquid chromatography (RP-HPLC) was used to purify these three neuropeptides before their analysis, radioimmunoassay (RIA) was used for the quantification of SP-like immunoreactivity (SP-LI), and liquid secondary-ion mass spectrometry (LSIMS) was used for the qualitative and quantitative analysis of ME and a tryptic peptide of BE. This study shows that, for 90% of the cases studied here (excluding one hypothyroidism case), the tachykinin A neuropeptide SP-LI level is decreased, the POMC peptide BE level is not altered, and the proenkephalin A neuropeptide ME level is increased in these PRL-secreting tumors.

There is a current trend toward nonsurgical therapy for small, minimally symptomatic acute subdural hematomas (ASDH), but data supporting such a scheme have been lacking. We evaluated 83 patients with minimally symptomatic ASDH (Glasgow Coma Scale scores of 11-15) and found 58 managed nonsurgically (70%) and 25 managed with craniotomy (30%). Patients managed without surgery had a lower incidence of focal neurologic deficits (12% vs. 40%; p < .01), open cisterns (90% vs. 28%; p < .001), and small (< or = 1 cm) ASDHs (92% vs. 62%; p < .001). Ninety-three percent of patients managed nonsurgically had functional recovery compared with 84% of patients with craniotomy. Age and injury Severity Score were significantly associated with patient outcome. Timing of surgery had no association with outcome. Six percent of patients managed nonsurgically developed chronic SDH requiring craniotomy. We conclude that unless the hematoma is causing clinical evidence of intracranial hypertension or significant neurologic dysfunction, there appears to be no advantage in evacuating the clot. Selected patients with ASDH and GCS scores of 11-15 can safely be managed without craniotomy.

Much evidence supports a fundamental role for mechanical forces in modulating differentiation, homeostasis, and remodelling of musculoskeletal cells. Little is known, however, regarding mechanobiology and gene expression of intervertebral disc (IVD) cells from older individuals. To characterise the effect of mechanical stimulation on cells from older discs, an in vitro study of IVD cells harvested from different aged pigs was conducted to measure extracellular matrix (ECM) gene expression in response to cyclic tensile stress (CTS). Gene expression of annulus fi brosus (AF) cells from IVDs of mature and older pigs was quantifi ed for the predominant ECM genes; type I collagen, type II collagen and aggrecan, and matrix metalloproteinase 1 (MMP-1), a collagenase that degrades fi brillar collagens. AF cells cultured on flexible-bottom plates were stretched 10 % at 0.5 Hz frequency. After 24 h, gene expression was assayed using reverse transcriptase polymerase chain reaction (RT-PCR). Basal mRNA levels without stretching for type II collagen and aggrecan were lower in older annular cells whereas MMP-1 levels were higher compared to mature cells. Following CTS, an adaptive response was elicited in annular cells from both age groups. ECM protein genes were upregulated, whereas MMP-1 was downregulated. The magnitude of response was signifi cantly greater in older cells as compared to mature cells. These data suggest that the cells from the AF of older animals manifest lower basal levels of mRNA for type II collagen and aggrecan and higher levels of MMP-1 possibly due to decreased tensile stress experienced in vivo and is not the result of reduced capacity for response.

Numerous studies have demonstrated an association between acute cardiac events, cerebrovascular accidents, and cocaine use. The underlying mechanisms leading to these complications have not been well defined. Using various in vitro model systems, it has been reported that cocaine, up to or greater than an order of magnitude of the lethal dose, causes either inhibitory or proaggregatory effects on platelet function. To address these reported discrepancies, we examined the effect of cocaine and its carrier on the activation and aggregation of human platelets in vitro. We found that cocaine inhibited platelet aggregation when platelets were challenged with ADP, collagen, or arachidonic acid. This inhibition was due to a direct effect on fibrinogen binding to the activated platelet. Cocaine also caused the dissociation of preformed platelet aggregates. At these same concentrations, cocaine did not inhibit agonist-mediated increases in cytosolic calcium or inhibit platelet shape change, suggesting that its effect on platelet aggregation was a selective process and not due to a total destruction of platelet function. Interestingly, the organization of the cytoskeleton of activated platelets, a secondary event critical to cell receptor clustering and clot retraction, was disrupted by cocaine treatment. In addition, alterations in platelet protein electrophoretic patterns were observed on preincubation of platelets with cocaine. We conclude that cocaine may have a direct inhibitory effect on the ability of platelets to participate in thrombus formation. The contribution of this effect as an underlying mechanism of sudden death in cocaine abusers is unknown.

✓ Spinal peridural fibrosis following total laminectomy in New Zealand White rabbits was significantly decreased by the intraoperative application of GT1587, a semi-synthetic carbohydrate polymer. The application of a similar polymer, GT1043, or phosphate-buffered saline (PBS) was not as effective. Laminectomies were performed at L-2 and L-4 in 25 rabbits. Absorbable gelatin sponge soaked with GT1043, GT1587, or PBS was applied in a blinded fashion to the operative sites, with untreated (sham) laminectomy sites serving as controls. Animals were sacrificed after 2 or 4 weeks. The extent of peridural fibrosis was evaluated by gross microdissection and histological analysis. Dense scar formation and dural adhesions were evident at both time intervals in the sham- and PBS-treated laminectomy sites. The sites treated with GT1587 showed significantly decreased peridural scar formation and dural adhesions, whereas GT1043 treatment caused modest reduction of scar formation at only the 2-week examination. The healing of skin and lumbosacral fascia was not affected by treatment of the laminectomy site with GT1587. These results suggest that GT1587 may prove beneficial in preventing postlaminectomy dural adhesions and peridural fibrosis in humans.

✓ A total of 93 patients with intractable spasticity due to either spinal cord injury (59 cases), multiple sclerosis (31 cases), or other spinal pathology (three cases) were entered into a randomized double-blind placebocontrolled screening protocol of intrathecal baclofen test injections. Of the 88 patients who responded to an intrathecal bolus of 50, 75, or 100 µg of baclofen, 75 underwent implantation of a programmable pump system for chronic therapy. Patients were followed for 5 to 41 months after surgery (mean 19 months). No deaths or new permanent neurological deficits occurred as a result of surgery or chronic intrathecal baclofen administration. Rigidity was reduced from a mean preoperative Ashworth scale score of 3.9 to a mean postoperative score of 1.7. Muscle spasms were reduced from a mean preoperative score of 3.1 (on a fourpoint scale) to a mean postoperative score of 1.0. Although the dose of intrathecal baclofen required to control spasticity increased with time, drug tolerance was not a limiting factor in this study. Only one patient withdrew from the study because of a late surgical complication (pump pocket infection). Another patient received an intrathecal baclofen overdose because of a human error in programming the pump. The results of this study indicate that intrathecal baclofen infusion can be safe and effective for the long-term treatment of intractable spasticity in patients with spinal cord injury or multiple sclerosis.

Expression of the vascular permeability factor/vascular endothelial growth factor (VEGPF) gene was investigated in human central nervous system (CNS) neoplasms and normal brain. Adsorption of capillary permeability activity from human glioblastoma multiforme (GBM) cell conditioned medium and GBM cyst fluids by anti-VEGPF antibodies demonstrated that VEGPF is secreted by GBM cells and is present in sufficient quantities in vivo to induce vascular permeability. Cloning and sequencing of polymerase chain reaction-amplified GBM and normal brain cDNA demonstrated three forms of the VEGPF coding region (567, 495, and 363 nucleotides), corresponding to mature polypeptides of 189, 165, and 121 amino acids, respectively. VEGPF mRNA levels in CNS tumors vs. normal brain were investigated by the RNase protection assay. Significant elevation of VEGPF gene expression was observed in 81% (22/27) of the highly vascular and edema-associated CNS neoplasms (6/8 GBM, 8/8 capillary hemangioblastomas, 6/7 meningiomas, and 2/4 cerebral metastases). In contrast, only 13% (2/15) of those CNS tumors that are not commonly associated with significant neovascularity or cerebral edema (2/10 pituitary adenomas and 0/5 nonastrocytic gliomas) had significantly increased levels of VEGPF mRNA. The relative abundance of the forms of VEGPF mRNA was consistent in tumor and normal brain: VEGPF495 > VEGPF363 > VEGPF567. In situ hybridization confirmed the presence of VEGPF mRNA in tumor cells and its increased abundance in capillary hemangioblastomas. Our results suggest a significant role for VEGPF in the development of CNS tumor neovascularity and peritumoral edema.

✓ The President of the American Association of Neurological Surgeons (AANS) validates the AANS as the national neurosurgical organization. He describes improved management of major committees of neurological surgery by the Joint Officers of the AANS and the Congress of Neurological Surgeons. A strong argument and proclamation are presented to expand the international role of the former Harvey Cushing Society.

✓ Glioblastoma multiforme, the most common and most lethal primary central nervous system neoplasm, is noted for its phenotypic and biological heterogeneity. This heterogeneity may result from genetic alterations accumulated by a single transformed astrocyte as it evolves into a monoclonal tumor. Alternatively, it may be attributed to the presence of multiple biologically and genetically distinct astrocytic populations within a polyclonal tumor. To address the issue of clonal composition of glioblastoma multiforme the authors used two independent approaches: analysis of X-chromosome inactivation and analysis of chromosomes 10 and 17 for tumor-specific somatic deletions. The analysis included 10 tumors from nine female patients with glioblastoma multiforme (eight primary and two recurrent tumors), who were heterozygous at either of two X-chromosome genes (hypoxanthine phosphoribosyl-transferase or phosphoglycerate kinase). Nine glioblastomas multiforme demonstrated a monoclonal pattern on X-chromosome analysis; contamination with normal tissue obscured the analysis in one tumor. Somatic deletions on chromosomes 10 and/or 17 occurred in nine tumors, supporting a monoclonal composition for these tumors. These data suggest that glioblastoma multiforme is a monoclonal neoplasm, derived from the clonal expansion of a single transformed astrocyte that has, as a fundamental step in tumorigenesis, sustained a critical genetic alteration on chromosome 10 and/or 17.

SummaryPlatelet aggregometry is often used to help diagnose storage pool disease (SPD-reduced amounts of granule nucleotides) and release defects (abnormal release of granule nucleotides). The general assumption that normal aggregation patterns are sufficient to rule out the diagnosis of one of these disorders has been invalidated by the recent publication of two papers describing patients with clinical bleeding, prolonged bleeding times and normal aggregation patterns in spite of defective release. The lumiaggregometer provides a tool for measuring platelet release and aggregation simultaneously. This paper presents a standardized, reproducible method for the use of the lumiaggregometer based on a “standard curve”. Data obtained during the development of the procedure are presented including normal ranges of release at different concentrations of agonists, release measured in intrinsic disorders as well as in patients on aspirin, and values for release relative to varying platelet counts. A monoclonal antibody (anti-p24/CD9; MAb7) which activates platelets similarly to thrombin and may be a useful reagent for distinguishing SPD and release defects is also introduced.

Background and Purpose—The reported prevalence of malnutrition after stroke varies widely, whereas it remains unclear which of the estimates is most accurate. The aim of this review was to explore possible sources of this heterogeneity among studies and to evaluate whether the nutritional assessment techniques used were valid.Methods—A literature search was conducted to identify all studies in which the nutritional state of patients was assessed after inpatient admission for stroke. The percentages of patients identified as malnourished in each study and method of nutritional assessment are reported. For the purposes of this study, an assessment technique was considered valid if at least one form of validity had been demonstrated previously through psychometric evaluation.Results—Eighteen studies meeting inclusion criteria were identified. The reported frequency of malnutrition ranged from 6.1% to 62%. Seventeen different methods of nutritional assessment were used. Four trials used previously validated assessment methods: Subjective Global Assessment, “an informal assessment,” and Mini Nutritional Assessment. The nutritional assessment methods used in the remaining studies used had not been validated previously.Conclusions—The use of a wide assortment of nutritional assessment tools, many of which have not been validated, may have contributed to the wide range of estimates of malnutrition. If so, this underscores the need for valid and reliable assessment tools to further our understanding of the relationship between stroke and nutritional status.

Lorazepam, antipyrine, and indocyanine green were administered to 10 patients with severe head injuries as marker substrates of hepatic glucuronidation, oxidation, and hepatic blood flow, respectively. Pharmacokinetic parameter estimates were determined at baseline (20 to 80 hours after injury) and up to three additional times thereafter (study days 4, 7, and 14). Antipyrine clearance was increased significantly from baseline (0.50 ± 0.31 ml/min/kg) on study days 4, 7, and 14 (p < 0.0001). Increases in antipyrine clearance from baseline to the last study day were observed in all study patients ranging from 14% to 207%. A significant increase was also observed in lorazepam clearance on study day 14 relative to baseline (1.39 ± 0.56 ml/min/kg) (p < 0.005). Increases in lorazepam clearance occurred in seven of nine patients over time ranging from 9% to 130%. The unbound fraction of lorazepam did not change significantly over the study period. Likewise, no significant change was observed in the clearance of indocyanine green over time. Antipyrine clearance and α1-acid glycoprotein (r = 0.41), and lorazepam clearance and C-reactive protein (r = −0.38) were significantly correlated (p < 0.05). Similarly, antipyrine and lorazepam clearances were significantly correlated with injury severity based on the Acute Physiologic and Chronic Health Evaluation (APACHE II) score (r = −0.43 and r = −0.37, respectively). These findings suggest that hepatic oxidative and conjugative metaboHsm increase significantly over time in patients after acute head injury. An awareness of the potential for pharmacokinetic alterations in similarly metabolized drugs used for patients with severe head injuries is recommended. Clinical Pharmacology and Therapeutics (1991) 50, 487–497; doi:10.1038/clpt.1991.173

To determine whether naturally occurring fatty acids, especially saturated ones, might act directly as vasodilators, segments of human basilar arteries and umbilical arteries were precontracted submaximally with prostaglandin F2 alpha and then exposed to different saturated fatty acids (C4 through C16) or unsaturated fatty acids (C14:1, C18:1, C18:2, and C18:3) at concentrations from 4 microM to 4 mM. The results showed caprate (C10) to be the most potent vasorelaxant and basilar arteries to be more responsive (EC50 = 63 microM) than umbilical arteries (EC50 = 780 microM). Caprate also inhibited contractions elicited by KCl, serotonin, and the thromboxane analogue U46619. The relaxation was independent of the endothelium, and potency was not related to the weak capacity of caprate to inhibit Ca(2+)-induced contractions of K(+)-depolarized basilar arteries. The pattern of potencies for the arteries differed, but among unsaturated fatty acids the monounsaturated (C14:1, C18:1) were more potent than the polyunsaturated (C18:2, C18:3). Comparing the potencies obtained with the concentrations reported for the free fatty acid content of arteries, brain, and plasma indicates that these lipids could influence vasomotion in health and disease.

The ocular microtremor (OMT) is mediated by the oculomotor area of the brainstem and is altered in several pathologic states, including traumatic brain injury, general anesthesia, brain death, coma, Parkinsonism and multiple sclerosis. The EYETECT tremor monitor is a non-invasive means of measuring the frequency and amplitude of this microscopic tremor. It has been clinically tested in these clinical scenarios and has been found to be a reliable means of detecting the depth of anesthesia, and has been useful in predicting outcome in coma and traumatic brain injury patients and in confirming brain death. This paper reviews the scientific literature on the EYETECT OMT monitor, describes the underlying physiology and discusses the potential for future works and clinical use of this innovative technology.

STUDY DESIGN: Mechanobiology study of gene expression changes as a result of compressive overload of anular fibrochondrocytes. OBJECTIVE: To test hypotheses regarding phenotype shift in genes coding for representative extracellular matrix (ECM) proteins and matrix modulators. SUMMARY OF THE BACKGROUND DATA: In degenerative disc disease, the transfer of compressive load through the disc shifts largely from the nucleus onto the anulus. In vivo models simulating this condition have shown derangement of the collagenous ultrastructure in the anulus. In vitro models of cultured anulus cells subjected to static compressive stress generally suggest a down-regulation of synthesis. This study evaluated the expression of specific isomers of genes responsible for mechanical viability and metabolism of the disc under cyclic compressive loads. METHODS: Fibrochondrocytes were digested from the anuli of 3, 2-week-old pigs, embedded in 1.5% alginate gel, and hydrostatically compressed at 0.5 Hz for 3 hours to amplitudes of 10 and 30 atm. These levels represented nominal load transfer through the healthy disc and high load transfer through the degenerative disc. Ribonucleic acid was isolated, reverse transcribed, and evaluated by real-time polymerase chain reaction for expression of type I (C-I) and type II (C-II) collagen, aggrecan, the matrix metalloproteinase (MMP-1), and the transforming growth factor beta (TGFbeta-1). Results were expressed at percentages of uncompressed controls. RESULTS: The lower pressure of 10 atm resulted in up-regulation of all ECM protein genes. C-I and C-II both averaged 141%, and aggrecan 121% of controls (P < 0.05). MMP-1 and TGFbeta-1 were essentially unchanged. With the pressure increased to 30 atm, C-II remained approximately at the level expressed under lower pressure, but C-I was reduced to 42% of controls (P < 0.05), indicating a phenotype shift. MMP-1 and TGFbeta-1 also were down-regulated to 71% and 54% of controls, respectively (P < 0.05). CONCLUSIONS: The up-regulation of the ECM genes with nominal pressure highlights the mechanobiological importance of common activity in fibrocartilage homeostasis. Differential regulation of the 2 primary collagen types with high pressure indicates a capacity of the anulus to remodel according to pathomechanical conditions.

Background context: Postsurgical epidural adhesions and fibrosis after surgery for lumbar disc herniation are a consequence of normal wound healing. The presence of fibrosis renders reoperations risky, and in some patients fibrosis may lead to nerve root tethering. Purpose: One approach to minimizing the risk of developing epidural adhesions is to provide a barrier between the dural membrane and the healing connective tissues. The purpose of these studies was to evaluate such a barrier device. Study design/setting: In vivo investigation in an animal model at a university laboratory. Patient sample: Rabbit. Outcome measures: Gross and histomorphic evaluation. Methods: Barriers comprised of carboxymethylcellulose (CMC) and polyethylene oxide (PEO) (Oxiplex; FzioMed, Inc., San Luis Obispo, CA) were studied as devices to reduce epidural adhesion formation in rabbit laminotomy and laminectomy models. The barriers tested were either a gel alone (gel) or a gel covered with a film (gel/film combination). Two laminotomy or laminectomy sites (depending on the surgical method) were created in each rabbit at L4 and L6. One site was treated with a CMC/PEO gel, or CMC/PEO gel/film combination, and the other site served as a surgical control. Two surgical models that differed in the extent of adhesion formation at untreated injury sites and the method of injury generation were used. Results: Model A, which did not incorporate dural abrasion, resulted in up to 40% adhesion-free laminectomy sites in controls. Model B, which did incorporate abrasion of the dural membrane, resulted in less than 10% adhesion-free laminotomy sites in controls. Compositions of CMC/PEO gels (2.5% to 10% PEO) and films (22.5% PEO) were tested in both models. Efficacy parameters included measuring the number of sites free of epidural fibrosis and reduction in the severity of fibrosis (adhesions). Both gels and gel/film combinations consistently reduced the frequency and the extent of epidural fibrosis in both models. Gels of CMC/PEO containing a higher content of PEO (10%) and a higher molecular weight of PEO (4.4 mD) were most effective in Model B and resulted in up to 84% laminotomy sites with minimal or no epidural fibrosis, whereas controls exhibited over 90% of the sites with epidural fibrosis. Histological evaluation of the surgical sites indicated that the reduction of epidural fibrosis was accompanied by normal bone healing. In addition, these experiments demonstrated that the gel/film combination provided no additional benefit to that obtained by the gel alone. Conclusions: Gels of CMC/PEO reduced epidural fibrosis and did not impair normal heal ing.

Study design In a porcine laminectomy model, a standard dural/arachnoid incision was made and tested for cerebrospinal fluid leak after material application. Sites were graded for scar formation and healing response at 3 weeks. Objective This study compares effectiveness of CoStasis, Tissucol, and suture for prevention of cerebrospinal fluid leaks and epidural scar formation after spinal dural incisions. Summary of background data Cerebrospinal fluid leaks following cranial and spinal surgery are potentially serious complications. Epidural scar formation is exacerbated by improper control of hemostasis. A hemostatic agent with dural sealant properties may be advantageous. Methods Total laminectomy was performed at three levels in seven pigs. At each level, a uniform 1.5 cm incision was made in the dura and arachnoid. A single suture was placed to approximate the edges and sites were treated with one of three methods: CoStasis, Tissucol, or no treatment. At sacrifice, 3 weeks later, epidural scar was graded, pressure testing of some sites was done, and tissue for histologic sections was harvested. Results CoStasis and Tissucol produced immediate dural sealing when the valsalva maneuver was applied. One suture-only site leaked. At sacrifice, all sites were sealed. CoStasis and Tissucol had less scar formation than control sites. Pressure testing results were similar at CoStasis and Tissucol sites. Conclusion CoStasis and Tissucol have comparable effectiveness in sealing CSF leaks immediately and at 3 weeks after complete laminectomy. CoStasis demonstrated comparable performance to Tissucol with less epidural scar formation than primary suture alone.

Patients with persistent low back pain (LBP) appear to be different in several important ways from patients who have traditionally been classified as patients with acute or chronic LBP, and data on the effectiveness of the treatments prescribed for them are lacking. The aim of the current study was to evaluate the short- and long-term effectiveness of the treatments currently prescribed for these patients. The data reported in this article were gathered as part of a multicenter, prospective, cross-sectional study of patients who were treated for persistent LBP by neurologic and orthopedic surgeons who are recognized specialists in spinal disorders. At enrollment, patients completed a baseline evaluation, and their physicians recorded relevant clinical and treatment data on standardized study forms. At 3, 6, 12, and 24 months after treatment, patients completed follow-up evaluations. Patients were divided into five treatment groups, and effectiveness was evaluated separately for each group using five patient-reported measures of outcome: pain severity, functional disability, psychologic distress, physical symptoms, and health care use. The data revealed that at the 2-year follow-up, the typical patient of the no-treatment group had improved slightly in terms of pain severity and health care use, but had experienced little or no improvement in functional disability, physical symptoms, and psychologic distress. The average patient in the conservative care group reported small improvements in pain severity, functional disability, physical symptoms, and health care use, with no change in psychologic distress. These small improvements occurred within the first 3 months after enrollment, with essentially no change thereafter. The average patient in the immediate surgical care group showed substantial improvement on all of the outcome measures. The observed improvements were evident shortly after treatment and were maintained for the duration of the study. Patients in the delayed surgical care group had outcomes that were less dramatic than those observed in the immediate surgery care group, but greater than those observed in the conservative care group. The patients who were treated surgically by physicians outside the study, outside surgical care group, did not improve over time. Patients with persistent LBP who received no treatment showed no spontaneous recovery. Conservative care treatments prescribed by surgeons who specialize in spinal disorders, did not appear to be any more effective than no treatment. The outcome of surgery for persistent LBP varied from dramatic for one subgroup of surgical patients, to poor for another subgroup of patients. Patients who were selected immediately for surgical treatment improved substantially. Those treated surgically later by study physicians or by physicians not associated with the study fared less well.

The objective of the Brain Tumor Cooperative Group NIH Trial 87-01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas.The study involved a randomized comparison of surgery, external beam radiotherapy, and carmustine (BCNU) versus surgery, external beam therapy, interstitial radiotherapy boost, and BCNU in newly diagnosed malignant gliomas. (125)I was chosen as best suited for this effort because it allowed preimplantation planning and postimplantation quality assurance review. Two hundred ninety-nine patients met the eligibility criteria and were randomized into the two arms of the study between December 1987 and April 1994. Follow-up continued for an additional 3 years. Twenty-nine patients were identified as having committed protocol violations and were excluded, resulting in 270 subjects in the Valid Study Group. One hundred thirty-seven patients received external beam radiation and BCNU, and 133 underwent the (125)I implantation plus external beam radiation and BCNU therapy.The overall median survival for the Valid Study Group was 64.3 weeks. The median survival for patients receiving additional therapy of (125)I was 68.1 weeks, and median survival for those receiving only external beam radiation and BCNU was 58.8 weeks. The cumulative proportion surviving between the two treatment groups was not statistically significantly different (log-rank test, P = 0.101). As in other studies in the literature, age, Karnofsky score, and pathology were predictors of mortality. Additional analyses incorporating an adjustment for these prognostic variables, either in a stratified analysis or Cox proportional hazards model, did not result in statistically significant differences in the cumulative proportion of patients surviving between the two treatment groups.We conclude that there is no long-term survival advantage of increased radiation dose with (125)I seeds in newly diagnosed glioma patients.

Anterior cervical discectomy with or without fusion is an acceptable surgical method for the treatment of cervical spondylosis or other spinal disc diseases. A spinal device may be used to immobilize the operated/injured region to promote bony fusion. Clinical studies have shown that motion at spinal segments adjacent to a fused region increases over time and may cause adjacent segment problems [Chow et al., 1996; Lee et al., 1988]. Multiple factors have been implicated, including the number of levels fused, health condition, post-operative alignment, and rigid fixation. An alternative approach to fusion surgery of the cervical spine is to restore the motion to the diseased joint using a movable artificial cervical joint (MACJ). The objective of the study was to determine the biomechanical stability of the harvested and instrumented cervical spine tested under physiologic flexion/extension and lateral bending loading mechanics. The instrumented spine consisted of a single level discectomy with subsequent disc replacement using a prototype artificial intervertebral disc implant by the Sofamor Danek Group, Memphis, TN.

✓ Intervertebral disc degeneration of any etiology may be associated with the formation of spaces or clefts within the disc. Gas collects within these spaces and can be seen roentgenographically. A case is presented in which intradiscal gas herniated into a connective tissue capsule, displacing the left S-1 nerve root and producing symptoms and signs identical to those of a herniated nucleus pulposus. The pathophysiology of gas within a disc space and the possibility that it may herniate much like the nucleus pulposus is discussed.

Object. Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). Methods. The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals); a treatment control group (SAH plus 2 µmol of the inactive drug carrier DETA, eight animals); a low-dose treatment group (SAH plus 0.2 µmol DETA/NO, six animals); or a high-dose treatment group (SAH plus 2 µmol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-µmol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals' brains were performed after the dogs were killed on Day 8. The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 µmol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p < 0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen. Conclusions. This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.

Stroke remains one of the major public health problems in the United States today, with approximately 500 000 new or recurrent cases occurring each year.1 About 4 000 000 persons alive today have survived a stroke and have some neurological deficits. Although the magnitude of healthcare resources used to treat and rehabilitate stroke survivors is considerable, to date a standardized, comprehensive classification system to document the resultant impairments and disability has not been developed. Successful management of any disabling disease, including stroke, should benefit from the use of a classification system to judge the impact of treatment, particularly emerging therapies. Participants in the Methodologic Issues in Stroke Outcome Symposium2 determined that the complex nature of stroke recovery demands clarification of its natural history and classification of the variable patterns of functional recovery. For stroke survivors to receive the best care, a comprehensive stroke outcome classification system is needed to direct appropriate therapeutic interventions.3 Building on the work and recommendations of the Stroke Outcome Symposium, the American Heart Association Classification of Stroke Outcome Task Force has worked to develop a valid and reliable global classification system that accurately summarizes the neurological impairments, disabilities, and handicaps that occur after stroke. The development of a stroke outcome classification system is predicated on the belief that neurological deficits often lead to permanent impairments, disabilities, and compromised quality of life.4 5 6 Although a person’s ability to complete daily functional tasks is thought to be largely dependent on and often limited by the type and degree of impairment, additional factors are often relevant in the ultimate determination of functional outcome.7 8 9 Thus, a classification of stroke outcome should include the broad range of disabilities and impairments as well as the relationship of disability and impairment to independent function. It …

Stroke remains one of the major public health problems in the United States today, with approximately 500 000 new or recurrent cases occurring each year.1 About 4 000 000 persons alive today have survived a stroke and have some neurological deficits. Although the magnitude of healthcare resources used to treat and rehabilitate stroke survivors is considerable, to date a standardized, comprehensive classification system to document the resultant impairments and disability has not been developed. Successful management of any disabling disease, including stroke, should benefit from the use of a classification system to judge the impact of treatment, particularly emerging therapies. Participants in the Methodologic Issues in Stroke Outcome Symposium2 determined that the complex nature of stroke recovery demands clarification of its natural history and classification of the variable patterns of functional recovery. For stroke survivors to receive the best care, a comprehensive stroke outcome classification system is needed to direct appropriate therapeutic interventions.3 Building on the work and recommendations of the Stroke Outcome Symposium, the American Heart Association Classification of Stroke Outcome Task Force has worked to develop a valid and reliable global classification system that accurately summarizes the neurological impairments, disabilities, and handicaps that occur after stroke. The development of a stroke outcome classification system is predicated on the belief that neurological deficits often lead to permanent impairments, disabilities, and compromised quality of life.4 5 6 Although a person’s ability to complete daily functional tasks is thought to be largely dependent on and often limited by the type and degree of impairment, additional factors are often relevant in the ultimate determination of functional outcome.7 8 9 Thus, a classification of stroke outcome should include the broad range of disabilities and impairments as well as the relationship of disability and impairment to independent function. It …

Object. To assess the effectiveness of Cummins' artificial cervical joint, the authors reviewed the cases of 20 patients in whom the joint had been placed. Methods. A review of patients' medical records and reexamination of 18 patients were performed. The review of the surgical experience with the implantation of movable stainless-steel joints in 20 patients treated for cervical myelopathy (16 patients), cervical radiculopathy (three patients), and severe pain (one patient) indicated that the procedure is safe and well tolerated and does preserve cervical joint motion in most patients over an extended period of observation. To date, adjacent segmental symptomatic degenerative changes leading to further surgical treatment have been avoided. The joint has been placed in patients with advanced congenital and acquired cervical fusion and has been demonstrated to be stable, mobile, and biomechanically and biochemically compatible; it has shown no subsidence into adjacent bone. Wear debris has not occurred. Conclusions. The use of stainless steel in the cervical spine appears to be suitable for this joint replacement design.