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Background: Ischemic stroke remains a major cause of disability with 90% of patients achieving no improvement after 90 days. The primary objective of this study was to evaluate the safety and feasibility of intraparenchymal administration of SB623 cells in chronic stroke. SB623 cells are adult bone-marrow-derived cells transfected with a plasmid encoding the intracellular domain of Notch-1 that have demonstrated improvement in functional testing in animal models of stroke. Methods: Patients with hemiparesis from stable subcortical ischemic stroke and NIHSS > 7 received intracranial injection of 2.5, 5 or 10 million SB623 cells. Clinical outcome measures included NIHSS, MRS, ESS and FMA measured at baseline and repeated at 6 and 12 months. FDG-PET was analyzed at each time point using cluster analysis within 5 regions of interest (contralateral frontal cortex, medial ventral to infarct, contralateral putamen, contralateral sensori-motor cortex, and contralateral thalamus). Results: Five patients enrolled at one academic center were included in this initial FDG-PET analysis. In these 5 patients, there was improvement in NIHSS (p = 0.008) and ESS (p = 0.006), which was most apparent from 0 to 6 months (p = 0.005; p = 0.005). There was also an increase in FDG-PET activity in the contralateral sensori-motor cortex from 0-6 months (p = 0.005), which was related to NIHSS, ESS and FMA (p = 0.043). Analyses of individual patients showed increased FDG uptake contralateral to the injection site in 3/5 patients. There was an increase near the area of infarct in 2/5 patients that was seen at 6 months but not at 12 months. Conclusions: Intraparenchymal injection of SB623 cells in chronic ischemic strokes resulted in increased FDG uptake predominantly in areas contralateral to stem cell injection in some patients. These increases were associated with improved clinical outcome measures suggesting that the PET changes might reflect activation of neural pathways due to stem cell therapy. Further PET studies with appropriate controls are warranted.

Introduction: No treatment exists to restore lost brain function after stroke. Animal studies demonstrate that brain transplantation of SB623, a human bone marrow derived stromal cell with transient transfection of Notch-1 gene, after experimental stroke can improve neurologic outcome. This clinical study is the first North American trial of intraparenchymal transplantation of bone marrow derived cell therapy for chronic stroke patients. METHODS: This is a two center (Stanford University and the University of Pittsburgh) open label safety and dose escalation feasibility study. Stereotactic transplantation is targeted to the subcortical peri-infarct area. Inclusion criteria include 18-75 yo, 6-60 mos post subcortical MCA ischemic stroke, mRS 3-4 and NIHSS > 7. Safety endpoints include WHO toxicity scale, MRIs and clinical follow-up to 2 years. The primary efficacy endpoint is European Stroke Scale (ESS) at 6 mos; secondary efficacy measures are ESS, NIHSS, Fugl-Meyer, mRS, cognitive scores up to 2 years, and FDG-PET at 6 months. RESULTS: Seventeen patients have been treated (6 with 2.5M cells, 6 with 5M and 5 with 10M). Follow-up is currently 6 mos in 12 pts, 9 mos in 9 pts and 12 mos in 6 pts. There were 3 serious adverse events related to the surgery, but not to the cells (seizure, subdural hematoma, pneumonia). Cytokine levels, HLA antibody levels, and PBMC function did not change from baseline. Three measures of efficacy (NIHSS, ESS, Fugl-Meyer) all show a trend toward improvement. Since the sample size is small, no statistical analysis has been done. Two patients showed remarkable improvement in their motor (2) and language function (1) within 24 h of surgery, effects which have been sustained during follow-up (12 and 3 mos). These were the only 2 patients with new FLAIR lesions (DWI neg) in the motor cortex that resolved at 2 mos. CONCLUSIONS: Intraparenchymal transplantation of human modified bone marrow derived stromal cells in chronic stroke patients is safe, feasible, and shows a trend toward neurologic improvement. Larger studies will be initiated to further assess clinical efficacy.

Object. The goals of this study were to analyze the accuracy of cytological techniques, consisting of touch and smear preparations, for the intraoperative diagnosis of stereotactically obtained brain biopsy samples, and to determine the prevalence of the use of these methods among neuropathologists.Methods. A survey regarding preferred methods for intraoperative diagnosis of stereotactically obtained brain biopsy samples was completed by 92 (62%) of 148 neuropathologists. Twenty-three percent of respondents chose frozen-section examination alone; 13% chose one or more cytological methods alone; and the remainder (64%) chose a combination of frozen-section examination and cytology.At the University of Pittsburgh, the neuropathology records for all stereotactic brain biopsies performed from May 1979 through May 1998 were retrospectively reviewed. Of the 946 stereotactic brain biopsies, 316 cases were excluded because the intraoperative neuropathological consultation was not recorded. Thirty-five cases were excluded because frozen-section examinations were performed. Therefore, a total of 595 cases were suitable for analysis.Intraoperative cytological investigation correlated with the final diagnosis in 90% of cases (52% complete correlation and 38% partial correlation). In 11% of cases there was no correlation between the intraoperative and final diagnoses. Intraoperative diagnoses were most accurate in cases of abscess, germinoma, lymphoma, metastasis, and malignant glioma.Overall, 91% of biopsy specimens were diagnostic when examined using the paraffin-embedded section technique. The sensitivity of cytological preparations in detecting a diagnostic specimen was 96% and the specificity in detecting a nondiagnostic specimen was 75%.Conclusions. Intraoperative cytological preparations correlated with the final diagnoses in 90% of stereotactic biopsies and had a 96% sensitivity in detecting diagnostic specimens. The highest rate of correlation was noted in cases of abscess, germinoma, lymphoma, metastasis, and malignant glial tumor.

Neurosurgeons must use accurate diagnostic techniques that confirm characteristics of individual glial neoplasms before recommending specific treatments. These diagnostic methods must reach all brain locations and be appropriate for patients of all ages and medical conditions. We believe that CT- or MR-based stereotactic biopsy is the best way to guide management in patients who do not require craniotomy for tumor mass effect. As our understanding of the biology of different tumors increases, we anticipate that even more specific therapeutic approaches will be developed that will require a histologic diagnosis and perhaps even new approaches to tumor classification and grading.

We distributed a questionnaire on radiosurgery patterns of practice to members of the International Stereotactic Radiosurgery Society (ISRS). Responses were obtained from physicians at 52 facilities, who had treated more than 13,000 patients. Most respondents were found to work within a multidisciplinary team, and averaged 17.3 specialist-hours devoted per patient on the day of radiosurgery. These results will enable radiosurgeons to determine if their practice differs from the norm and to adjust their practice standards, if appropriate.

Swedish neurosurgeon Lars Leksell, frustrated by the invasiveness of existing surgical tools and the morbidity some neurosurgical patients endured, created the field of stereotactic radiosurgery in 1951. He subsequently pioneered the development of the dedicated multi-source Cobalt 60 Gamma Knife. During the 27 year interval from its first clinical use in 1967 to its latest application in 1994, single fraction, closed skull irradiation of deep intracranial targets has been performed in more than 20,000 patients worldwide. The goals of radiosurgery are obliteration or prevention of further growth of the target coupled with reduced patient risk in comparison to more invasive procedures.

Image guided brain surgery became a reality in the mid-1970s after the introduction of the first methods to obtain axial imaging using computed tomography (CT) [9]. The recognition of cranial disease much earlier in its clinical course prompted the need for concomitant minimally invasive technologies to both diagnose and to treat the newly recognized brain tumors and vascular malformations. Subsequently, the development of magnetic resonance imaging (MRI) spurred further interest in accurate, safe, and effective guided brain surgery. Stereotactic radiosurgery (SRS) was the brains child of the pioneering brain surgeons, Lars Leksell and Erik-Olof Backlund at the Karolinska Institute [4, 5]. Stereotactic guiding devices were adapted to newly evolving imaging techniques, ranging from encephalography to angiography, CT, and MRI. These new techniques prompted further evaluation of stereotactic radiosurgery, a field envisioned by Leksell in 1951. His concept that ionizing radiation could be cross fired to destroy or inactivate deep brain targets without a surgical opening proved to be an enormous step forward in minimally invasive surgery. Under the watchful eye of Leksell, Gamma knife technologies gradually expanded in their role and their usage exploded across the field of neurosurgery [1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 13].

The Presbyterian-University Hospital of Pittsburgh installed the first clinically designated Leksell gamma knife in the U.S. in August 1987. Gamma knife radiosurgery involves stereotactic target localization with the Leksell frame and subsequent closed-skull single-treatment session irradiation of a lesion with multiple highly focused gamma ray beams produced from 60Co sources. The hemispherical array of sources, the large number of small-diameter beams, and the steep dose gradients surrounding a targeted lesion make physical characterization of the radiation field complex. This paper describes the physical features and the operation of the gamma knife as well as the calibration procedures of the very small, well-collimated beams. The results of studies using in-phantom ion chamber, diode, film, and lithium fluoride thermoluminescent dosimetry were all in close agreement. Both single-beam and multiple-beam dose profiles were measured and reported for the interchangeable helmets, which have 4-, 8-, 14-, and 18-mm-diameter collimators. We also describe the dose calculation and treatment planning algorithm in the treatment planning system. Measurements of the accuracy of mechanical and radiation alignment are also performed and discussed.

Patients who have an acoustic neuroma (vestibular schwannoma) can be managed with observation, open surgical resection, stereotactic radiosurgery, or fractionated radiotherapy. Increasing numbers of patients are choosing radiosurgery over resection for their tumor. In this report we discuss the history of stereotactic radiosurgery, and the evolution in technique that has led to current results with this approach. We discuss the indications for and expectations with the different treatments. The literature on radiosurgery and radiotherapy is reviewed. It is expected that clinical and basic studies will further improve results.

Stereotactic radiosurgery using the 201 Cobalt-60 source Gamma Knife has been an effective method for obliterating selected cerebral arteriovenous malformations (AVMs). For more than 20,000 patients worldwide, angiography under stereotactic conditions has been the main imaging modality for defining and targeting the AVM nidus. The role of angulation of the X-ray tube for angiographic localization of the AVM during stereotactic Gamma Knife radiosurgery was studied with a phantom. Using current dose-planning software, tube angulation facilitated target visualization, improved three-dimensional dose planning, and has been consistent with the increased probability of complete nidus obliteration.

Multiple brain metastases (BrM) are a common challenge to patients with cancer. Tumour resection is used mainly for patients with large tumours that cause acute neurological syndromes. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than six months. For this reason, numerous centres have evaluated the role of stereotactic radiosurgery (SRS) in patients with solitary or multiple tumours. We conducted a randomised trial that compared radiosurgery plus WBRT to WBRT alone. The rate of local failure at one year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was six months after WBRT alone in comparison to 36 months after WBRT plus radiosurgery (p=0.0005). The median time to any brain failure was improved in the radiosurgery group (p=0.002). Survival was related to extent of extracranial disease (p=0.02). Combined WBRT and radiosurgery for patients with two to four BrM significantly improves control of brain disease. WBRT alone, for years the standard treatment, does not appear to provide lasting and effective care for most patients. Controversies remain in patient selection, number of BrM suitable for treatment, concomitant management of extracranial disease, and timing of therapy.

AVM radiosurgery has been in practice for over 30 years and is now a common method to manage properly selected patients with brain AVMs. The techniques have been refined along with our understanding of the expected response. It is this understanding of expected outcomes that should allow a rational discussion of the pertinent issues for management of patients with AVMs. Some patients will require multimodality approaches. All AVM patients should seek to understand whether stereotactic radiosurgery is an appropriate option for their problem.

Radiosurgery is a surgical procedure associated with minimal functional morbidity and allows patients to return rapidly to their previous level of activity. Most tumors regress in volume with extended follow-up, and the rare occurrence of tumor growth after radiosurgery seems to occur early. Similarly, cranial neuropathy or other neurologic symptoms after irradiation occur within the first few years and are usually mild and transient. Current results indicate a low rate of cranial neuropathy (lower than with any other technique). Useful hearing preservation in patients with NF2 seems to be an attainable goal with more sophisticated radiosurgery techniques. We anticipate the increased use of stereotactic radiosurgery for patients with vestibular schwannomas as more and more smaller sized tumors are identified.

To better predict permanent complications from arteriovenous malformation (AVM) radiosurgery.Data from 85 AVM patients who developed symptomatic complications following gamma knife radiosurgery and 337 control patients with no complications were evaluated as part of a multi-institutional study. Of the 85 patients with complications, 38 patients were classified as having permanent symptomatic sequelae (necrosis). AVM marginal doses varied from 10-35 Gy and treatment volumes from 0.26-47.9 cc. Median follow-up for patients without complications was 45 months (range: 24-92).Multivariate analysis of the effects of AVM location and the volume of tissue receiving 12 Gy or more (12-Gy-Volume) allowed construction of a significant postradiosurgery injury expression (SPIE) score. AVM locations in order of increasing risk and SPIE score (from 0-10) were: frontal, temporal, intraventricular, parietal, cerebellar, corpus callosum, occipital, medulla, thalamus, basal ganglia, and pons/midbrain. The final statistical model predicts risks of permanent symptomatic sequelae from SPIE scores and 12-Gy-Volumes. Prior hemorrhage, marginal dose, and Marginal-12-Gy-Volume (target volume excluded) did not significantly improve the risk-prediction model for permanent sequelae (p/= 0.39).The risks of developing permanent symptomatic sequelae from AVM radiosurgery vary dramatically with location and, to a lesser extent, volume. These risks can be predicted according to the SPIE location-risk score and the 12-Gy-Volume.

Stereotactic radiosurgery has been shown in small clinical series to reduce or abolish seizures in patients with lesion-related or idiopathic epilepsy. The radiation dose necessary to eliminate epileptogenesis is unknown, and the histological and metabolic effects of radiosurgery remain undefined. We hypothesized that in a rat model of kainic acid-induced hippocampal epilepsy, radiosurgery could provide a significant reduction in seizure frequency while limiting biochemical and structural histological damage to the brain.Kainic acid (8 g) was injected into the rat hippocampus using stereotactic targeting. Focal seizures so generated were identified with scalp and depth electroencephalography (EEG). Epileptic rats were randomized to a control group (n = 20) and to radiosurgery groups in which maximum doses of 20, 40, 60, or 100 Gy (8-9 animals per group) were administered. Over a 42-day period, seizure frequency was determined by direct observation for 8 hours per week. Scalp EEG was performed weekly in all animals. Magnetic resonance imaging (MRI) studies (T1- and T2-weighted water-proton and quantitative sodium images) were obtained on Days 7, 21, and 42.As compared with the control group, treated animals showed significant reductions in the number of seizures during each successive week after 20-Gy radiosurgery (P = 0.01-0.002). When we combined the number of seizures observed in the latter half of the study (Weeks 4-6), we found a significant reduction in seizures after 20-Gy (P = 0.007), 40-Gy (P = 0.03), 60-Gy (P = 0.03), and 100-Gy (P = 0.03) radiosurgery as compared with control animals. Increasing doses of radiosurgery correlated with higher percentages of rats that became seizure-free by EEG criteria. MRI-determined total sodium concentration in the injected hippocampus was 49.8+/-3 mmol/L, compared with 42.8 mmol/L on the contralateral side (within normal limits). This significant increase in sodium concentration was present in control rats (because of the kainic acid) and did not change with increasing radiosurgery dose. No parenchymal effects from radiosurgery were identified after 20, 40, and 60 Gy, and only two rats had necrosis at 100 Gy. All animals showed hippocampal injury from kainic acid by proton MRI and histological examination.In this rat hippocampal epilepsy model, stereotactic radiosurgery was followed by a significant dose-dependent reduction in the frequency of observed and EEG-defined seizures. These effects were not accompanied by increased radiation-induced structural or metabolic brain injury as assessed by proton and sodium MRI or histological examination. The role of radiosurgery as a new, nondestructive surgical therapy for idiopathic epilepsy warrants further investigation.

Neurosurgeons must use accurate diagnostic techniques that confirm characteristics of individual glial neoplasms before recommending specific treatments. These diagnostic methods must reach all brain locations and be appropriate for patients of all ages and medical conditions. We believe that CT- or MR-based stereotactic biopsy is the best way to guide management in patients who do not require craniotomy for tumor mass effect. As our understanding of the biology of different tumors increases, we anticipate that even more specific therapeutic approaches will be developed that will require a histologic diagnosis and perhaps even new approaches to tumor classification and grading.

Advances in noninvasive diagnostic techniques have enabled physicians to diagnose acoustic tumors early, while hearing is still present. Applications of advanced operative techniques have allowed surgeons to decrease progressively the operative mortality to virtually zero, to save facial nerve function in a large number of patients, and even to preserve serviceable hearing in selected patients. Documented improvement in hearing after acoustic tumor surgery is rare. During the last decade, stereotactic radiosurgery has evolved as a noninvasive surgical option for acoustic tumors. Hearing improvement after radiosurgery has not been reported. The authors observed hearing improvement in 21 out of 487 patients who had radiosurgery during a 10-year interval. This article reviews their experience of hearing improvement after radiosurgery and suggests possible reasons that hearing can not only be retained but also improved in selected patients.

The indications for and results after meningioma radiosurgery results are discussed. Particular emphasis is placed on longer-term results, the evolution of technique, complications, and recommendations regarding the role of radiosurgery together with other management strategies.

Selection of the prescription dose for radiosurgery is the final step in treatment planning. Dose selection should take into account the expectation of treatment success (i.e., tumor control, arteriovenous malformation [AVM] obliteration, and so forth) and complication risks at various doses. Accurately predicting complication risks for individual patients is a complex process that is highly dependent on the radiosurgery treatment volume, the target location, and the nature of the target tissue. Dose-response data for desired outcomes of radiosurgery are sparse and difficult to interpret for most indications, with perhaps the exception of AVM obliteration. This article reviews the principles governing dose-selection and the evolving body of data guiding dose selection in radiosurgery.

Stereotactic radiosurgery is an important treatment option for arteriovenous malformations (AVMs) and hemorrhagic cavernous malformations. Radiosurgery is effective in obliterating AVMs and preventing rebleeding of cavernous malformations with two or more hemorrhagic episodes. Outcome analyses of radiosurgery for these vascular malformations have provided important information to improve the safety and effectiveness of radiosurgical treatment.

The increased use of ablative movement disorder surgery, pallidotomy, and thalamotomy must be followed by our better understanding of regional neuroanatomy, use of imaging and physiologic techniques for targeting, and methods of lesion creation. The safety of these techniques has been established; efficacy will require additional studies. Selection of appropriate patients and our understanding of outcomes will assist the surgeon in choosing between ablative surgeries and other forms of management.

A retrospective study of patients undergoing stereotactic radiosurgery for one to four brain metastases from nonsmall lung cell carcinoma (NSCLC) was performed to document outcomes and risks.Seventy-seven patients underwent radiosurgery during a 7-year interval; 71 also underwent whole brain radiation therapy. Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival.The overall median survival was 10 months after radiosurgery, and 15 months from the diagnosis of brain metastases. Five factors significantly affected survival: extent of systemic disease, presence of a neurologic deficit, size of the intracranial tumor, initial imaging appearance of intratumoral necrosis, and initial resection of the primary tumor of the chest. Median survival time was 26 months in a subgroup of patients with no extracranial metastases, no neurologic deficits, and a small tumor without necrosis. The authors evaluated 91 tumors with imaging. Local tumor control was achieved in 77 lesions (85%) and tumoral radiation necrosis developed in 4 lesions (4.4%). Nineteen new metastatic tumors developed during the observation interval.Stereotactic radiosurgery for NSCLC brain metastases is effective and is associated with few complications. The early detection of brain metastases and treatment with radiosurgery combined with radiation therapy provide the opportunity for extended high quality survival.

Despite the establishment of the vasculoneural compression as a frequent cause of trigeminal neuralgia, minimally invasive surgical techniques to treat medically refractory trigeminal neuralgia are needed in order to minimize the risks associated with craniotomy. Percutaneous retro gasserian glycerol rhizotomy (PRGR) is one of the alternative surgical treatments to microvascular decompression. Technical simplicity, less chance of trigeminal sensory loss, no need of intraoperative sensory testing, and no attempted deliberate destruction of the trigeminal nerve are advantages over other percutaneous trigeminal operations.

Radiosurgery is one of the surgical treatments of trigeminal neuralgia. Through precise irradiation of the proximal trigeminal nerve identified on high-resolution imaging, pain relief can be achieved after a short latency interval. This image-guided approach has been useful for both patients with persistent pain after other surgeries, and as a primary surgical option. A minimum dose of 70 Gy delivered with the gamma knife has been associated with low risk for facial numbness, and no other morbidity. Management of trigeminal neuralgia without an incision, transfacial needle placement or nerve section may prove useful to increasing numbers of patients.

Stereotactic radiosurgery is effective in controlling brain metastasis at presentation and those that recur after radiotherapy. It is the treatment of choice for most patients with small solitary brain metastasis by virtue of its low morbidity, high-effectiveness, and cost.

We evaluated the role of stereotactic radiosurgery (SRS) in 25 children with surgically incurable brain tumors of glial origin. Histological diagnoses were obtained at the time of craniotomy and attempted removal (n = 20) or by stereotactic biopsy (n = 5). Thirteen children had tumors with benign histological characteristics (pilocytic and low-grade astrocytomas), whereas 12 children had tumors with malignant characteristic (malignant astrocytomas and ependymomas). Eleven (10 with malignant tumors) of the 25 children had received fractionated irradiation before SRS. Radiosurgical doses (range to margin, 11-20 Gy) were calculated on the basis of tumor volume and location, with consideration given to prior radiation dose. Follow-up for the 13 children with benign tumors ranged from 6 to 48 months (median, 21 mo). Eleven of the 13 children with "benign" glial neoplasms had tumor control with SRS alone (no evidence of tumor, n = 4; decreased tumor, n = 5; and unchanged tumor, n = 2), and all 13 remain alive. Five children with malignant tumors are alive at 12, 45, 50, 72, and 72 months after radiosurgery. The other seven children with malignant tumors are dead, with a median survival of 6 months after radiosurgery. Three of 12 children with malignant glial neoplasms had tumor control after SRS. Two of these three children received fractionated irradiation as an adjunct to SRS. Complications occurring in four children were transient, associated with peritumoral edema, and responsive to oral glucocorticoids. There was no relationship between tumor volume and local control after radiosurgery. Radiosurgery alone is a safe and effective treatment modality for unresectable benign gliomas of childhood. Radiosurgery may have a role in the adjuvant management of unresectable malignant glial neoplasms of childhood if other therapies (irradiation or chemotherapy) are available.

To analyze the effect of stereotactic radiosurgery on the hemorrhage rate of arteriovenous malformations (AVMs), we reviewed the clinical and angiographic characteristics of 315 patients with AVMs before and after radiosurgery. One hundred ninety-six patients sustained 263 bleeds in 10,939 patient-years before radiosurgery, for an annual nonfatal hemorrhage rate of 2.4%. Clinical follow-up after radiosurgery was available in 312 patients (mean, 47 +/- 20 mo); follow-upor = 24 months was obtained in 295 patients (94%). Twenty-one patients had AVM bleeds at a median of 8 months (range, 1-60 mo) after radiosurgery. Two additional patients had three aneurysmal bleeds (at 5, 27, and 32 mo, respectively) for a 7.4% total risk of hemorrhage per patient. The actuarial hemorrhage rate until AVM obliteration was 4.8% per year (95% confidence interval, 2.4-7.0%) during the first 2 years after radiosurgery and 5.0% per year (95% confidence interval, 2.3-7.3%) for the third to fifth years after radiosurgery. Multivariate analysis of clinical and angiographic factors demonstrated that the presence of an unsecured proximal aneurysm was associated with an increased risk of postradiosurgical hemorrhage (relative risk, 4.56; 95% confidence interval, 1.77-11.70%; P0.001). No AVM hemorrhages were observed after radiosurgery in seven patients with intranidal aneurysms. No protective effect against hemorrhage was observed in patients who received an "optimal" radiation dose (or = 25 Gy to the AVM margin) compared with patients who received25 Gy to the AVM margin (P = 0.36). No patient suffered a hemorrhage after angiography had confirmed complete obliteration (n = 140) or suffered from an early draining vein without residual nidus (n = 19). Stereotactic radiosurgery was not associated with a significant change in the hemorrhage rate of AVMs during the latency interval before obliteration. No protective benefit was conferred on patients who had incomplete nidus obliteration in early (60 mo) follow-up after radiosurgery. AVM patients with unsecured proximal aneurysms should have aneurysms obliterated either before radiosurgery or at the time of surgical resection of their AVMs.

This article reviews the authors' experience with image-guided surgery for brain metastases and discusses specifically the impact of the frameless viewing wand system on standard craniotomy techniques for this disorder. Topics discussed include patient selection, interactive image-guided neurosurgical resection of brain metastases, and other image-guided neurosurgical systems.

Treatment options for head and neck cancers that recur at the cranial base are limited.Twelve patients with head and neck cancers recurrent after resection and fractionated radiotherapy (n = 11) at the cranial base had stereotactic radiosurgery using the gamma unit. The median dose to the tumor margin was 16 Gy. Imaging follow-up varied from 3 to 17 months; the longest clinical follow-up was at 35 months.Three of 8 tumors studied by postradiosurgery imaging remained unchanged in size, 3 decreased, and 2 were no longer visible. There was no morbidity or worsening of symptoms after radiosurgery. Four patients died between 4 and 8 months and did not have postradiosurgery imaging performed. Mean survival after radiosurgery was 10.5 months, with 7 patients (58%) still living.Radiosurgery proved safe and effective in providing local control for recurrent cranial base cancers arising from the extracranial head and neck. Radiosurgery should be considered for those patients who have failed prior fractionated radiation or surgical resection, those who have tumors in high-risk cranial locations, or those who are poor medical candidates. Although this study shows its potential adjuvant role, longer follow-up and increased clinical experience will be necessary to evaluate the overall role of radiosurgery in head and neck cancer.

Stereotactic radiosurgery is an increasingly safe and usually effective method of preventing growth of small to moderate-sized primary tumors of the anterior skull base. Tumor growth control is obtained in more than 90% of patients with skull base tumors having benign histology. Neurologic function is maintained in most patients. The risk of temporary or permanent injury to critical neural and vascular structures is significantly lower than the risk associated with microsurgery. The optic nerves, chiasm, and tracts are structures that appear most sensitive to the radiation doses used during radiosurgery of anterior skull base tumors. The incidence of injury to the optic apparatus is low when the dose to the nerve is less than 8 to 9 Gy (27). The incidence of injury to motor nerves, such as the oculomotor, trochlear, trigeminal, and abducens nerves, is extremely low at the doses used in clinical radiosurgery (27). To date no cases of delayed carotid injuries have been reported. Microsurgical complications (e.g., CSF leak, wound infection, and meningitis) do not occur after radiosurgery. Additional attractive features of radiosurgery are a relatively low, hospital-based cost and a rapid return of the patient of work. In the report of our experience with the first 207 patients treated with the Gamma Knife at the University of Pittsburgh, the average length of hospital stay was 2.24 days for a patient undergoing stereotactic radiosurgery for a skull base tumor and 11.44 days for a patient undergoing craniotomy for the same lesion. The total hospital charges were 30 to 70% lower for patients having radiosurgery (19). The average hospital stay and cost of radiosurgery are even lower now, because most radiosurgery patients are released from the hospital on the same day as their procedure. Patients are usually able to return to a full preoperative functional level and employment within 3 to 5 days. There are patients in certain clinical situations in which microsurgery clearly is required. These include patients experiencing rapidly progressive visual deterioration or who have endocrine-active pituitary tumors. A more rapid reduction in endocrine dysfunction is best achieved by microsurgical tumor excision. In patients in whom a tumor recurs despite "gross total removal," and in cases in which tumor is left behind to preserve critical nerve and vessel integrity, stereotactic radiosurgery is a very effective alternative to additional microsurgical operations. Stereotactic radiosurgery may also be the primary treatment of choice in patients who are unable or unwilling to accept the risk:benefit ratio of microsurgery.

We believe that every patient who has clinical symptoms and neurodiagnostic imaging signs suggesting a low-grade glial neoplasm should undergo early diagnosis and treatment. Observation is not warranted for a tumor that has a median survival of 5 years. The value of cytoreductive surgery for many patients has yet to be proven. It is incumbent on neurosurgeons who advocate this approach to show that this more aggressive treatment strategy is preferable to minimally invasive techniques, such as stereotactic biopsy followed by radiation therapy. Clearly, some patients who have a glial tumor require early cytoreductive surgery: those with mass effect and significant neurologic deficits. Otherwise, they will not be able to tolerate fractionated radiation therapy. Because the long-term survival rate is very poor, observation is not warranted in patients with suspected glial neoplasm. Early stereotactic biopsy immediately identifies those patients who, in fact, have more anaplastic tumors and a much worse prognosis. Such patients may benefit from early, aggressive treatments such as cytoreductive surgery, chemotherapy, and radiation. Applying this philosophy, we have achieved a median survival of more than 10 years in patients with astrocytoma. Most patients maintain a high KPS rating, and most do not require delayed cytoreductive surgery. Although we believe that the outcomes of future patients with astrocytomas will improve, we must establish whether such improvement is related to better therapeutic options, earlier recognition enabled by advanced neuroimaging, or the availability of corticosteroids (28, 30). We also believe that neurosurgeons and neuro-oncologists should stop arguing over whether cytoreductive surgery is warranted. For some patients it is, and for others it is not. This prolonged controversy indicates the basic impotence with which neurosurgeons approach glial tumors. Our energy and efforts should be devoted toward more concrete and positive goals in terms of glial tumor management. These goals include prolonged and higher-quality survival, reduced surgical and postoperative morbidity, and the development of new surgical, chemotherapeutic, and molecular tools that will allow us to improve clinical outcomes. Needless and senseless arguing over cytoreductive surgery versus biopsy, radiation versus no radiation, or any of these procedures versus observation alone trivialize the issues that face us and our patients: astrocytomas of the brain are neither indolent nor benign. The vast majority of our patients with astrocytomas are dead within 5 years, and almost all within 10. Our papers, our meetings, our approach should encourage us to pursue new basic science and clinical strategies to fight glial neoplasms. Surgery alone cures no patient with a glioma. Radiation therapy cures relatively few, and chemotherapy cures none. New ideas and new approaches are needed to improve the plight of our patients.

We compared the efficacy and the hospital charges of either single-stage or two-stage stereotactic diagnosis and radiosurgery procedures. Twelve patients underwent either one-stage or two-stage diagnosis and management of their brain tumors. Both techniques utilize high-resolution intraoperative stereotactic image-guided technology and rapid touch preparation (imprint) cytopathological techniques to confirm the presence of neoplasm. Following this pathologic diagnosis, six patients immediately underwent stereotactic radiosurgery employing the same frame application and dose planning based on preoperative and intraoperative images. Six patients underwent two-stage procedures, i.e., discharge from the hospital after histopathological diagnosis followed by readmission, reapplication of the stereotactic head frame, and repeat neuroradiological imaging prior to radiosurgery. Requirements for success of the single-stage procedure include intraoperative stereotactic high-resolution imaging, a hospital-wide ethernet system for transferring neurodiagnostic images, and expertise in rapid touch-preparation histopathological technique for accurate diagnosis. Intraoperative computed tomography imaging after biopsy confirmed the target accuracy and lack of movement of the target after brain biopsy. The advantages of the single-stage approach include reduced length of overall hospital stay, simultaneous histopathological diagnosis and therapy in a single hospital admission, and reduced total hospital charges. For patients highly suspected of having brain tumors and for whom stereotactic radiosurgery will be utilized in the treatment, single-stage stereotactic diagnosis immediately followed by radiosurgery is an accurate, effective, and potentially less costly management strategy than a two-stage approach.