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This article chronicles the development of real-time ultrasound for use in operations in the central nervous system. Described are the technology and the various applications of ultrasound in the neurosurgical operating room. The use of real-time ultrasound to localize, characterize, and instrument lesions of the brain and spinal chord are discussed.

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In this study we describe the technique of intraoperative ultrasound imaging of brain and spinal cord in trauma patients. The images are shown and their interpretation is discussed. This intraoperative imaging allows for localization of hematomas, bone fragments and indriven foreign bodies (i.e., pieces of plastic, glass, metal, etc.). Disc material and bone fragments deep to the spinal cord can be localized with this technique. Real-time ultrasound can be used to guide instruments within the brain and, thereby, provide dynamic guidance for removal of bone fragments and foreign bodies dynamically. In summary, intraoperative real-time ultrasonic imaging is of use to the neurosurgeon in the treatment of the neurotrauma patient.

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The accuracy of a novel frameless stereotactic system was determined during 10 surgeries performed to resect brain tumors. An array of three charge-coupled device cameras tracked the locations of infrared light-emitting diodes on a hand-held stylus and on a reference frame attached to the patient's skull with a single bone screw. Patient-image registration was achieved retrospectively by digitizing randomly chosen scalp points with the system and fitting them to a scalp surface model derived from magnetic resonance (MR) images. The reference frame enabled continual correction for patient head movements so that registration was maintained even when the patient's head was not immobilized in a surgical clamp. The location of the stylus was displayed in real-time on cross-sectional and three-dimensional MR images of the head; this information was used to predict the locations of small intracranial lesions. The average distance (and standard deviation) between the actual position of the mass and its stereotactically predicted location was 4.8 +/- 3.5 mm. The authors conclude that frameless stereotaxy can be used for accurate localization of intracranial masses without resorting to using fiducial markers during presurgical imaging and without immobilizing the patient's head during surgery.

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The survival rate for patients with malignant gliomas is poor. We describe the results of a prospective study using concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for patients with malignant gliomas. Forty-two patients with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were treated with postoperative photon radiation 45 Gy/25 fraction (fxs) with concomitant continuous intravenous infusion of 5-fluorouracil at 300 mg/m2/day x 5 days and hydroxyurea 0.5 g orally every 12 hr for 6 days for 5 consecutive weeks, followed by a neutron boost of 450 N cGy/6 fxs delivered twice weekly. Adjuvant chemotherapy with procarbazine, CCNU, and vincristine (PCV) was given up to 1 year or until tumor progression. Thirty-four patients (81%) had GBM and 8 patients (19%) had AA. Sixteen patients (38%) were ineligible for the neutron boost because of large tumors or poor performance status and instead received a photon boost with concomitant chemotherapy for a total dose of 60-65 Gy to the tumor. The overall median survival is 68 weeks at a median follow-up of 203 weeks (range 166-302 weeks for the 11 patients remaining alive); 7/8 patients with AA are alive, 2 of these with progressive disease. For AA the median survival is not reached at a median follow-up of 203 weeks (range 166-302 weeks for the 7 patients alive with AA). Time to tumor progression for the 1 dead patient with AA was 35 weeks and the other 2 patients failed at 171 weeks and 179 weeks following treatment. The median survival for the 34 patients with GBM was 62 weeks; 4/34 patients with GBM are alive at 285, 238, 216, and 206 weeks. Multivariate survival analysis in the 34 patients with GBM revealed age and Karnofsky performance status as important prognostic factors. Extent of surgery and neutrons did not affect survival. Concomitant chemoradiotherapy was well tolerated by all patients. The only toxicities observed were mucositis < or = grade II in 3 patients (7%) and mild myelosuppression in 1 patient (2.4%). Adjuvant PCV was well tolerated. Continuous concomitant chemoradiotherapy was well tolerated by all patients with acceptable side effects. The survival rate for the patients with GBM suggests no significant impact on the prognosis for these patients. Patients with AA did well; however, the patient numbers are small.

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A frameless stereotactic device interfacing an electromagnetic three-dimensional (3-D) digitizer to a computer workstation is described. The patient-image coordinate transformation was found by retrospectively registering a digitizer-derived model of the patient's scalp with a magnetic resonance (MR) imaging-derived model of the same surface. This procedure was performed with routine imaging data, eliminating the need to obtain special-purpose MR images with fiducial markers in place. After patient-image fusion was achieved, a hand-held digitizing stylus was moved over the scalp and tracked in real time on cross-sectional and 3-D brain images on the computer screen. This device was used for presurgical localization of lesions in 10 patients with meningeal and superficial brain tumors. The results suggest that the system is accurate enough (typical error range 3 to 8 mm) to enable the surgeon to reduce the craniotomy to one-half the size advisable with conventional qualitative presurgical planning.

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Two glioma tumor lines and specimens from five patients with gliomas were analyzed to determine genic expression of four growth factors found in human brain. Messenger RNA encoding for interleukin-1 beta, interleukin-6, and basic fibroblast growth factor was found to be expressed in significant amounts in some of these tumors, while mRNA for interleukin-3 was found in small quantities in only the tumor lines. Multiple species of mRNA for basic fibroblast growth factor were found. Expression of growth factor genes may play a role in the growth of human gliomas.

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The transfacial approach to the anterior cranial fossa for tumor removal provides for excellent surgical exposure, improved postoperative appearance, and a minimum of complications. The technique is different from previously reported combined craniofacial ablative procedures in that the head and neck surgeon and the neurosurgeon approach the anterior fossa mass through the same facial incision, thus avoiding the need for a separate craniotomy incision. The formation of a vascularized nasofrontal bone flap allows for better wound healing regardless of preoperative and postoperative radiotherapy and/or chemotherapy. This report presents 42 cases in which the transfacial approach was exclusively used in a combined manner to remove nasal, paranasal sinus, and nasopharyngeal neoplasms. The transfacial technique offers a significant advantage over previously described approaches to the anterior skull base.

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Through the technical advances in molecular biology during the past decade, important new insights into the fundamental chromosomal changes associated with brain tumors have been gained. The pace of such research is accelerating, and most of the published reports have appeared outside the neurosurgical literature. Furthermore, many neurosurgeons may not be sufficiently familiar with the terminology and techniques involved to remain abreast of the field. In this review, we discuss through specific examples of recent work on brain tumors the basic techniques of molecular biology, including the Southern and Northern blots, restriction enzyme digestion of DNA, molecular cloning of genes, and mapping of chromosomal deletions. Gene amplification and rearrangements are discussed through review of recent work on the N-myc gene in neuroblastoma and the epidermal growth factor receptor (EGFR) gene in glioblastoma. The molecular cloning of the gli gene from a glioblastoma illustrates the powerful analytic nature of these laboratory techniques and the investigative potential of a cloned gene. The concept of the "recessive oncogene" is discussed through a summary of recent work analyzing restriction fragment length polymorphisms (RFLPs) in families of patients with meningioma, acoustic neurinoma, and bilateral acoustic neurofibromatosis (BANF; NF-2). Throughout this article, emphasis is placed on ways in which molecular biology may soon affect clinical practice.

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In an attempt to investigate the role of tissue fibrinolytic activity in the resolution of intracerebral hematoma, an experimental model of intracerebral hematoma was developed in the rat. The fibrinolytic activity was studied using a histochemical fibrin slide technique. A total of 59 adult male rats were studied. Twenty-nine rats were used for developing the intracerebral hematoma model via injection of autologous whole blood into the left frontal lobe; in the remaining 30 rats, the intracerebral hematomas were studied sequentially. Intracerebral hematoma formation was unsuccessful in six (21%) of 29 rats. Four rats died in the immediate postoperative period and two showed no intraparenchymal clot. Intense fibrinolytic activity was demonstrated in the blood vessel walls of the normal brain, especially in the meninges, choroid plexus, and ependymal cell layer. In the initial stages of hematoma resolution, fibrinolytic activity was not seen in the hematoma or parenchyma except in the preexisting blood vessels. However, 3 to 5 days later, fibrinolytic activity was observed in the capillary buds surrounding the hematoma and among the infiltrating mononuclear cells. This activity increased for 7 to 10 days following formation of the hematoma and decreased after 21 to 28 days. It is concluded that tissue fibrinolytic activity associated with newly formed blood vessels appears to be important in lysis of intracerebral hematomas.

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The pathophysiology of cervical spondylotic myelopathy and syringomyelia is incompletely understood. Only 50-60% of the former group of patients and only 30-40% of the latter group of patients show long-term improvement. One possible cause for this might be continued anterior compression of the spinal cord in the former and incomplete drainage of the fluid-filled cavities in the latter. Intraoperative ultrasound imaging can be done in the operating room (4-6, 16-18) and can identify whether an adequate decompression has been done in patients with cervical spondylotic myelopathy and whether there has been complete drainage in shunting of patients with syringomyelia. Intraoperative ultrasound imaging aids the neurosurgeon in checking to see if he did what he set out to do. It is useful in operative procedures for cervical spondylotic myelopathy and syringomyelia.

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Glucose utilization in vivo and hexokinase activity and mitochondrial oxygen consumption in vitro were measured in a series of human brain tumors. Several relatively slow-growing tumors appeared to have depressed electron-transport activities coupled with a compensatory elevated glucose utilization. These data suggest that a decrease in oxidative metabolism and a corresponding increase in glycolysis are not necessarily correlated with malignancy in certain human brain tumors.

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It has been recognized for some time that malignant cells have a diminished respiratory rate coupled with an excessive rate of aerobic glycolysis. Subsequent studies indicated, however, that this pattern was neither unique to malignant tumors nor an essential characteristic of all varieties of cancer. In attempting to synthesize the data on oxygen consumption of human brain tumors, it is difficult to relate activity to malignancy, and the integrity of the mitochondrial electron transport chain has not been systematically examined. In this study, oxygen consumption was measured using a whole cell mixture and subsequently with isolated mitochondria prepared by routine differential centrifugation from a variety of human brain tumors. It is clear from these data that low oxidative respiration is not uniquely characteristic of malignant tumors, but that a number of benign tumors such as meningiomas and pituitary adenomas display very low levels of oxygen consumption. Many of these tumors have normal respiration, with isolated mitochondria using substrates that enter at different points in the electron transport pathway. However, several of the tumors in this series showed defects in respiration at various points in the electron transport pathway. These data suggest that both benign and malignant brain tumors have depressed respiratory capacities secondary to either a decrease in mitochondria per cell or defects in electron transport activities.

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The significance and management of cervical carotid artery tortuosity are controversial. One hundred eighteen cases of angulation of the common carotid artery and over 800 cases of elongation of the internal carotid artery have been reported. The etiology, presentation, diagnosis, and treatment of each entity are reviewed. Angulation of the common carotid artery is often managed conservatively. For clarity, elongations of the internal carotid artery should be classified as either tortuosities or kinks. Some patients with kinks of the internal carotid artery will have episodes of cerebrovascular insufficiency related to the position of their heads. Such patients merit thorough diagnostic evaluation. When other etiologic factors have been eliminated, patients in this group may benefit from a surgical procedure directed at the vascular abnormality. Applicable surgical techniques are discussed.

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The efficacy of intraoperative neurosurgical ultrasound (US) scanning was determined in studies of 191 lesions (186 patients). US was deemed to have played a useful role in operations on 101 (53%) of these lesions, including 66 (49%) of the 136 brain tumors. The main utility of US imaging was in locating subcortical masses, but it also proved useful in identifying residual tumor after resection; locating cysts within tumors; delineating surrounding vascular structures; and locating subcortical cysts, hematomas, arteriovenous malformations, and inflammatory masses or abscesses. In light of these findings, US study appears to have a place in many intracranial operations.

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Patients with cerebral ischemia comprise an extremely heterogeneous group that makes analysis of treatment extremely difficult. Given the wide range of findings in the literature, one may select specific reports to justify a predetermined viewpoint. The study of Easton and Sherman has elicited a disproportionate amount of attention. Of the thousands of reported patients in the literature, this study of 228 patients with high postoperative morbidity and mortality has regrettably been cited often as the potential representative of surgical outcome in community hospitals. Undoubtedly, surgical skill varies and may affect results. Not all studies, however, support the contention that such procedures can only be performed adequately by surgeons who frequently do such operations. Most importantly, this study should redraw our attention to the fact that the success of the individual surgeon must be evaluated for any given procedure. With proper selection of patients, both carotid endarterectomy and EC-IC bypass procedures have proved to be safe and effective. In general, technical advances have heralded surgical results that appear to be superior to medical management, or no treatment, in a wide range of patients with cerebrovascular disease. Surgical results can only be evaluated when a procedure is fully developed technically and a large number of cases are accumulated. For carotid endarterectomy, and more recently EC-IC bypass, the necessary information is becoming available. However, the classification of patients to which these procedures should be applied has lagged behind. Given the variability in patients with cerebrovascular disease, this is somewhat understandable. Properly controlled studies would necessarily be unrealistically large. However, the technology and subsequent data that should be developed throughout the next decade will provide us with important information about brain ischemia and metabolism. This new technology should allow us to more completely define the exact nature of ischemic events in the individual patient. This will lead to better classification of patients and, ultimately, will improve patient selection for any methods of treatment, either medical or surgical.

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Thoracic disc herniation is uncommon. An incidence of 0.25 to 0.75 per cent of protruded disks are in the thoracic region. A peak incidence is noted in the fourth decade with 75 per cent of the protruded disks occurring below T8. Pain is the most common initial symptom, present in 57 per cent of the cases, followed by sensory disturbances and motor involvement. By the time of diagnosis, 90 per cent of the patients have signs of spinal-cord compression. Although myelography has been considered the test of choice, 8 per cent false negative results and a correct preoperative diagnosis of 56 per cent has been reported. Now, with CT scanning with and without metrizamide, more accurate diagnoses can be achieved, even with cases in which myelography is negative. There has been a considerable improvement in the surgical treatment of herniated thoracic disks with over an 80 per cent rate of success for surgical approaches other than the posterior approach (decompressive laminectomy). An early and accurate diagnosis, coupled with improvement in the surgical approach, offers a much better prognosis for patients with thoracic disk herniation.

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Intraoperative real-time ultrasound imaging in the neurosurgical operating room is most useful in localizing, characterizing, and guiding the instrumentation of lesions of the brain and spinal cord. In the future, more and more operative procedures will be done using intraoperative ultrasound guidance. The ultrasound scanner, as developed for neurosurgery, will become another instrument in the neurosurgeon's armamentarium.

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