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Molecular biology and neurosurgery in the third millennium.

The application of techniques in molecular biology to human neurosurgical conditions has led to an increased understanding of disease processes that affect the brain and to novel forms of therapy that favorably modify the natural history of many of these conditions. Molecular strategies are currently being either used or sought for brain tumors, stroke, neurodegenerative diseases, vascular malformations, spinal degenerative diseases, and congenital malformations of the central nervous system. Considering that the structure of deoxyribonucleic acid was ascertained by Watson and Crick as recently as 1953, the progress that has been made to implement molecular medicine in clinical practice has been meteoric. More than 2000 patients have been treated in approved gene therapy trials throughout the world. Many of these patients have been treated for neurological diseases for which conventional medical therapies have been of limited utility. As part of this continuing series on advances in neurosurgery in the third millennium, we first reflect on the history of the nascent field of molecular biology. We then describe the powerful techniques that have evolved from knowledge in this field and have been used in many publications in Neurosurgery, particularly within the past decade. These methods include commonly used techniques such as advanced cytogenetics, differential display, microarray technology, molecular cell imaging, yeast two-hybrid assays, gene therapy, and stem cell utilization. We conclude with a description of the rapidly growing field of bioinformatics. Because the Human Genome Project will be completed within 5 years, providing a virtual blueprint of the human race, the next frontier (and perhaps our greatest challenge) will involve the development of the field of "proteomics," in which protein structure and function are determined from the deoxyribonucleic acid blueprint. It is our conviction that neurosurgeons will continue to be at the forefront of the treatment of patients with neurological diseases using molecular strategies, by performing essential research leading to increased understanding of diseases, by conducting carefully controlled studies to test the effects of treatments on disease processes, and by directly administering (by neurosurgical, endovascular, endoscopic, or stereotactic means) the treatments to patients.

Cytogenetics↗

Neurosurgery at the University of Pennsylvania Medical Center.

The University of Pennsylvania Medical School was the nation's first medical school, and its Department of Neurosurgery is one of the nation's oldest. The history of the Department of Neurosurgery at Penn is recounted, beginning with the pioneer surgeon Charles Harrison Frazier. The evolution of the current department, its contemporary status, and its residency program are described.

Academic Medical Centers↗

The early history of neurosurgery in the American South.

As a specialty, neurosurgery was not on firm footing at the turn of the century (1900); however, it was brought into being in the American South early in the 20th century by seven young surgeons, all of whom performed neurosurgical procedures as part of their general surgery practice. A close look at the seven reveals that they were trained and/or influenced in varying degrees by either Dr. Harvey Cushing or Dr. Victor Horsley, two outstanding surgeons and teachers of this period. After overcoming many obstacles, these seven men firmly established the surgical specialty of neurosurgery in the South.

History, 20th Century↗

Biological plasticity: the future of science in neurosurgery.

THE FUTURE OF neurosurgery is intimately related to the future of neuroscientific research. Although the field of neuroscience is immense and not subject to brief review, it is clear that certain trends have become critical to future thinking regarding neurosurgery. An important theme that recurs in much of the current research and that will become more prominent in the future is the concept of plasticity. This refers not only to the changes in cortical representation that can occur after a variety of perturbations but also to a wide variety of neurologically relevant biological processes. In this review, we describe three areas of plasticity, i.e., the response of the brain to ischemia, cortical representational changes, and the potential for stem cell biological processes to allow us to manipulate plasticity. We posit that these trends will be crucial to the future of our specialty.

Hematopoietic Stem Cell Transplantation↗

Sine qua non: the formulation of a theory of neurosurgery.

Fundamental postulates underlying the fabric of biomedicine are rarely discussed, much less seen in print. Scientific surgery and its subspecialties are relatively new fields, and their philosophical basis has received little attention since Halsted's day. During the last quarter century, we have "reinvented" neurosurgery, and a concatenation of forces is escalating that is further accelerated by technological change. Social, economic, political, and scientific climates concurrently exert unusually stressful influences on all practitioners, irrespective of the individual setting. This provides a reason to reexamine what neurosurgeons do and why, and to attempt to define the guidelines of theoretical basis for the specialty of neurosurgery and its procedures. This article examines the accomplishments of past generations in an effort to establish surgical substrata and proceeds to attempt to readdress elements of a theoretical basis of our current practice.

Humans↗

Microelectromechanical systems and neurosurgery: a new era in a new millennium.

MICROMACHINES AND MICROELECTROMECHANICAL SYSTEMS (MEMS) are terms that are new to neurosurgeons but certain to become "household terms" in neurosurgery in the near future. These new terms serve as an introduction to a new world of sensors, actuators, and "smart systems" that will change the ways in which neurosurgeons interact with their environment. Through the use of microelectronics and micromachining technologies, MEMS will allow neurosurgeons to perform familiar tasks with greater precision, perform tasks that previously were not done at all, and monitor physiological and biochemical parameters more accurately and with greater safety. This review provides the information necessary to understand the fundamental concepts of MEMS and their application to the neurosurgical arena. It defines the relevant terms and describes the history behind the "micromachine revolution," the capabilities and limitations of MEMS technology, and how this revolution is germane to neurosurgery and to neurosurgeons.

Artificial Intelligence↗

The genesis of neurosurgery and the evolution of the neurosurgical operative environment: part II--concepts for future development, 2003 and beyond.

The future development of the neurosurgical operative environment is driven principally by concurrent development in science and technology. In the new millennium, these developments are taking on a Jules Verne quality, with the ability to construct and manipulate the human organism and its surroundings at the level of atoms and molecules seemingly at hand. Thus, an examination of currents in technology advancement from the neurosurgical perspective can provide insight into the evolution of the neurosurgical operative environment. In the future, the optimal design solution for the operative environment requirements of specialized neurosurgery may take the form of composites of venues that are currently mutually distinct. Advances in microfabrication technology and laser optical manipulators are expanding the scope and role of robotics, with novel opportunities for bionic integration. Assimilation of biosensor technology into the operative environment promises to provide neurosurgeons of the future with a vastly expanded set of physiological data, which will require concurrent simplification and optimization of analysis and presentation schemes to facilitate practical usefulness. Nanotechnology derivatives are shattering the maximum limits of resolution and magnification allowed by conventional microscopes. Furthermore, quantum computing and molecular electronics promise to greatly enhance computational power, allowing the emerging reality of simulation and virtual neurosurgery for rehearsal and training purposes. Progressive minimalism is evident throughout, leading ultimately to a paradigm shift as the nanoscale is approached. At the interface between the old and new technological paradigms, issues related to integration may dictate the ultimate emergence of the products of the new paradigm. Once initiated, however, history suggests that the process of change will proceed rapidly and dramatically, with the ultimate neurosurgical operative environment of the future being far more complex in functional capacity but strikingly simple in apparent form.

Forecasting↗

Transcranial Doppler ultrasonography with induction of anesthesia for neurosurgery.

Intracranial hypertension can occur with induction of anesthesia; however, the clinical significance of this is unclear. We used transcranial Doppler (TCD) ultrasonography in neurosurgical patients during induction of anesthesia and endotracheal intubation to assess the incidence of high intracranial pressure (ICP) waveforms and to correlate TCD observations with specific anesthetics and anesthetic regimens. The middle cerebral artery was monitored by TCD during induction of anesthesia and endotracheal intubation in 196 patients undergoing elective neurosurgery. Middle cerebral artery blood flow velocity (MCABFV) and physiologic data were observed continuously and recorded at the following times: preinduction, induction, intubation, and postintubation. Induction with thiopental or etomidate decreased MCABFV, intubation increased MCABFV, and postintubation ventilation decreased MCABFV. MCABFV was higher throughout the induction sequence in the 92 patients with tumors. Although there were numerous individual exceptions, changes in mean arterial pressure correlated statistically with changes in MCABFV. No patient had an end-diastolic flow velocity of 0. We reached the following conclusions: (a) TCD is a straightforward modality that can be used to monitor dynamic cerebrovascular events during induction of anesthesia; (b) MCABFV is increased with brain tumors; (c) thiopental and etomidate rapidly decrease and intubation rapidly increases MCABFV; and (d) routine TCD monitoring for high ICP waveforms during anesthetic induction for routine elective neurosurgery appears to be unwarranted.

Adult↗

Neurosurgery in Papua New Guinea.

BACKGROUND: An audit of neurosurgery in Papua New Guinea (PNG) based on the experience of a visiting neurosurgeon is presented. The objectives of the study were to determine the type and frequency of neurosurgical conditions in PNG, whether major neurosurgery can be performed successfully in PNG, and to develop a strategy for the development of neurosurgical services in PNG. METHODS: The audit was carried out over two periods of 2 weeks duration in 1992 and 1993 in Port Moresby and Goroka. Instrumentation and equipment were limited and no additional equipment was used. Myelography and angiography were available in Port Moresby. RESULTS: There were 82 patients in total, 55 (67.1%) were consultations, 23 (28%) had elective surgery, four (4.8%) had emergency surgery and 16 (19.5%) await surgery. Cases were subdivided into nine major groupings: neurotrauma 18 (seven severe); spine 18; congenital 13; hydrancephaly four; scalp, skull and orbit six; vascular three; peripheral nerve three; and neurology five. Seventy-two (87.8%) patients required CT/MRI which were unavailable. Four ventriculograms were performed in lieu of CT/MRI. Fifteen (18.3%) cases could not be treated in PNG. CONCLUSIONS: Neurosurgical problems in PNG can often be adequately managed with limited resources. Complex procedures were performed with gratifying results and acceptable morbidity. There is sufficient pathology in a country of four million people to justify training a small number of neurosurgeons by the end of the decade. CT scanning will be a necessary adjunct.

Adult↗

Dynamics of serum procalcitonin in patients after major neurosurgery.

Classical markers of infection cannot differentiate reliably between inflammation and infection after neurosurgery. This study investigated the dynamics of serum procalcitonin (PCT) in patients following major neurosurgery. PCT concentrations remained < 0.2 ng/mL during the post-operative course. In contrast, leukocyte and neutrophil counts, as well as C-reactive protein (CRP) levels, increased significantly post-operatively (leukocytes, range 7.1-23.7 x 10(9)/L, p < 0.001; neutrophils, range 70.8-94.5%, p < 0.001; CRP, median 14 mg/L, range 3-95 mg/L, p < 0.001). Analysis of PCT levels using assays with improved sensitivity may be useful in the diagnosis of neurosurgical patients with post-operative fever of unknown origin.

Adult↗

Severe head injury in children: emergency access to neurosurgery in the United Kingdom.

OBJECTIVE: To determine the scale of acute neurosurgery for severe traumatic brain injury (TBI) in childhood, and whether surgical evacuation for haematoma is achieved within four hours of presentation to an emergency department. METHODS: A 12 month audit of emergency access to all specialist neurosurgical and intensive care services in the UK. Severe TBI in a child was defined as that necessitating admission to intensive care. RESULTS: Of 448 children with severe head injuries, 91 (20.3%) underwent emergency neurosurgery, and 37% of these surgical patients had at least one non-reactive and dilated pupil. An acute subdural or epidural haematoma was present in 143/448 (31.9%) children, of whom 66 (46.2%) underwent surgery. Children needing surgical evacuation of haematoma were at a median distance of 29 km (interquartile range (IQR) 11.8-45.7) from their neurosurgical centre. One in four children took longer than one hour to reach hospital after injury. Once in an accident and emergency department, 41% took longer than fours hours to arrive at the regional centre. The median interval between time of accident and arrival at the surgical centre was 4.5 hours (IQR 2.23-7.73), and 79% of inter-hospital transfers were undertaken by the referring hospital rather than the regional centre. In cases where the regional centre undertook the transfer, none were completed within four hours of presentation-the median interval was 6.3 hours (IQR 5.1-8.12). CONCLUSIONS: The system of care for severely head injured children in the UK does not achieve surgical evacuation of a significant haematoma within four hours. The recommendation to use specialist regional paediatric transfer teams delays rather than expedites the emergency service.

Adolescent↗

Informed consent in neurosurgery--translating ethical theory into action.

OBJECTIVE: Although a main principle of medical ethics and law since the 1970s, standards of informed consent are regarded with great scepticism by many clinicans. METHODS: By reviewing the reactions to and adoption of this principle of medical ethics in neurosurgery, the characteristic conflicts that emerge between theory and everyday clinical experience are emphasised and a modified conception of informed consent is proposed. RESULTS: The adoption and debate of informed consent in neurosurgery took place in two steps. Firstly, respect for patient autonomy was included into the ethical codes of the professional organisations. Secondly, the legal demands of the principle were questioned by clinicians. Informed consent is mainly interpreted in terms of freedom from interference and absolute autonomy. It lacks a constructive notion of physician-patient interaction in its effort to promote the best interest of the patient, which, however, potentially emerges from a reconsideration of the principle of beneficence. CONCLUSION: To avoid insufficient legal interpretations, informed consent should be understood in terms of autonomy and beneficence. A continuous interaction between the patient and the given physician is considered as an essential prerequisite for the realisation of the standards of informed consent.

Attitude of Health Personnel↗

Threats to academic neurosurgery in the United Kingdom: a personal view.

Money, or lack of it, is but one, albeit very important, threat to academic neurosurgery. This review has rambled over some of the other minefields and self-inflicted hurdles. The path of academic progress is long and tortuous. Time has to be found in neurosurgery to examine critically the opportunities and threats posed by a changing world to our goals of establishing standards of patient care, research, and the flexible training of the next generation.

Budgets↗

Acute intraoperative brain herniation during elective neurosurgery: pathophysiology and management considerations.

OBJECTIVES: To describe operative procedures, pathophysiological events, management strategies, and clinical outcomes after acute intraoperative brain herniation during elective neurosurgery. METHODS: Review of clinical diagnoses, operative events, postoperative CT findings, intracranial pressure, and arterial blood pressure changes and outcomes in a series of patients in whom elective neurosurgery had to be abandoned because of severe brain herniation. RESULTS: Acute intraoperative brain herniation occurred in seven patients. In each patient subarachnoid or intraventricular haemorrhage preceded the brain herniation. The haemorrhage occurred after intraoperative aneurysm rupture either before arachnoidal dissection (three) or during clip placement (one); after resection of 70% of a recurrent hemispheric astroblastoma; after resection of a pineal tumour; and after a stereotactic biopsy of an AIDS lesion. In all patients the procedure was abandoned because of loss of access to the intracranial operating site, medical measures to control intracranial pressure undertaken (intravenous thiopentone), an intraventricular catheter or Camino intracranial pressure monitor inserted, and CT performed immediately after scalp closure. The patients were transferred to an intensive care unit for elective ventilation and multimodality physiological monitoring. Using this strategy all patients recovered from the acute ictus and no patient had intracranial pressure > 35 mm Hg. Although one patient with an aneurysm rebled and died three days later the other six patients did well considering the dramatic and apparently catastrophic nature of the open brain herniation. CONCLUSIONS: There are fundamental differences in the pathophysiological mechanisms, neuroradiological findings, and outcomes between open brain herniation occurring in post-traumatic and elective neurosurgical patients. The surprisingly good outcomes in this series may have occurred because the intraoperative brain herniation was secondary to extra-axial subarachnoid or intraventricular haemorrhage rather than intraparenchymal haemorrhage or acute brain oedema. Expeditious abandonment of the procedure and closure of the cranium may also have contributed to the often very satisfactory clinical outcome.

Adult↗

Pediatric neurosurgery work force: a pilot study.

The physician work force of tomorrow is influenced by the number of physicians and specialists trained today. Little information exists about the need for pediatric neurosurgeons in the next 10 years or about the activity of pediatric neurosurgeons currently in practice. The objective of this study was to obtain preliminary data about pediatric neurosurgeons and current work loads. A questionnaire was distributed to physicians attending the Pediatric Section Meeting of the American Association of Neurological Surgeons, 1997, 93 questionnaires were returned. A majority of the respondents were between 35 and 55 years of age. The largest group geographically was from the northeast. Fifty-five respondents described their practice as academic and of that group, 48% reported that their practice was either exclusively or at least 95% pediatric neurosurgery. Self-described work load varied with geographic location. In the northeast, only 26% of practitioners felt they were not busy enough, whereas in the southwest, 60% reported not being busy enough. Academic practitioners were more likely than other respondents to describe their practice as too busy or appropriately busy. Thirty-six respondents indicated plans to either expand their practice or retire within the next 10 years. This pilot study demonstrates the potential for future growth in pediatric neurosurgery as well as providing information about the current self-reported work load and its distribution over practice types and geographic locations. This study provides guidance for development of future studies to improve the sensitivity and usefulness of acquired data.

Adult↗

High-field strength interventional magnetic resonance imaging for pediatric neurosurgery.

BACKGROUND: Interventional magnetic resonance (MR) imaging allows neurosurgeons to interactively perform surgery using MR guidance. High-field (1.5-Tesla) strength imaging provides exceptional visualization of intracranial and spinal pathology. The full capabilities of this technology for pediatric neurosurgery have not been defined or determined. MATERIALS AND METHODS: From January 1997 through June 1998, 10 of 85 cases performed in the interventional MR unit were in the pediatric population (mean age 8.3, median 8, range 2-15 years). Procedures included 2 brain biopsies, 5 craniotomies for tumor, 2 thoracic laminectomies for syringomyelia, and placement of a reservoir into a cystic brainstem tumor. The biopsies and reservoir placement were performed using MR-compatible equipment. Craniotomies and spinal surgery were performed with conventional instrumentation outside the 5-Gauss magnetic footprint. Interactive and intraoperative imaging was performed to assess the goals of surgery. RESULTS: Both brain biopsies were diagnostic for cerebral infarct and anaplastic astrocytoma and the reservoir was optimally placed within the tumor cyst. Of the 5 tumor resections, all were considered radiographically complete. One biopsy patient and 1 tumor resection patient experienced transient neurological deficits after surgery. The patient with the thoracic syrinx required reoperation when the syringosubarachnoid shunt migrated into the syrinx 3 months after initial placement. No patient sustained a postoperative hemorrhage. Tumor histologies found at craniotomy were craniopharyngioma, ganglioglioma, and 3 low-grade gliomas. No evidence of tumor progression has been seen in any of these patients at a mean follow-up of 5.3 (range 4-8) months. The goals of the procedure were achieved in all 10 cases. There were no untoward events experienced related to MR-compatible instrumentation or intraoperative patient monitoring, despite the present inability to monitor core body temperature. CONCLUSIONS: 1.5-Tesla interventional MR is a safe and effective technology for assisting neurosurgeons to achieve the goals of pediatric neurosurgery. Preliminary results suggest that surgical resection of histologically benign tumors is enhanced in the interventional MR unit. The incidence of surgically related morbidity is low.

Adolescent↗

Molecular neurosurgery for glial and neuronal disorders.

Molecular neurosurgery is the surgical use of molecules to destroy, sustain, or modulate or augment neurons, supporting cells or tumor cells within the nervous system. Molecules designed for surgical use may be engineered to be used in their molecular state or may be packaged as liposomes, viruses or genetically engineered cells. This article summarizes the current state of development of one aspect of molecular neurosurgery--the use of genetically engineered viruses to treat brain tumors. Both herpes virus and retrovirus strategies are discussed. Each virus has its own set of advantages and disadvantages that can be used in the design of an appropriate therapeutic strategy. Further application of this technology to intrinsic glial and neuronal disorders is discussed, and future perspectives are presented.

Brain Diseases↗

MRI distortion and stereotactic neurosurgery using the Cosman-Roberts-Wells and Leksell frames.

When not corrected, geometrically distorted magnetic resonance images may be unsuitable for stereotactic intracranial neurosurgical procedures where accuracy of target localization is critical. On a GE Signa 1.5-tesla system, we implemented an imaging protocol designed to improve the accuracy of the determination of target coordinates by means of multiple scans utilizing reversal of the frequency-encoded readout gradient. Using a Cosman-Roberts-Wells (CRW) frame and a phantom, geometric shifts of important image features were found to occur. In patients undergoing functional neurosurgical procedures with the CRW system, localization of the posterior commissure by corrected MR images was compared to that obtained by intraoperative ventriculography. Unexpectedly, severe distortions in MR images were revealed by the studies, with shifts of some fiducial markers of 10 mm from their estimated true position. Most of this distortion was attributable to the magnetic properties of the stereotactic frame, and could be eliminated by appropriate design and manufacture of the frame system. Images obtained with an MRI-compatible Leksell stereotactic frame were found to be relatively free of major geometric distortion. This study points out that properties of frame systems used for stereotactic neurosurgery may greatly influence the accuracy of frame-based stereotactic neurosurgery, and that the accuracy of these frame systems is testable.

Humans↗