Interim report on the radiosurgical treatment of cerebral arteriovenous malformations. The influence of size, dose, time, and technical factors on obliteration rate

During the authors' initial 4-year experience with radiosurgery using the Leksell cobalt-60 gamma unit, they treated 121 patients with cerebral arteriovenous malformations (AVMs). The radiosurgical dose to the margin of the nidus was 20 Gy for lesions less than 2.0 cm in diameter (volume < or = 4.2 cm3); 18 Gy for malformations 2.1 to 3.0 cm in diameter (volume 4.2-14.1 cm3); and 16 Gy for malformations greater than 3.0 cm (volume > 14.1 cm3). Fifty-one patients underwent follow-up angiography between 1 and 3 years after treatment, and complete obliteration of the nidus was confirmed in 38 (74.5%) of these patients. Thirty-two (74.4%) of 43 AVMs with volumes of 10 cm3 or less and six (75%) of eight larger AVMs (volume 11-30 cm3) showed complete obliteration. Analysis of the time course of AVM nidus shrinkage and obliteration showed that most of the radiosurgically induced effect had occurred by 36 months after treatment. Retrospective analysis of the dose plans for 10 AVMs that were not obliterated by 36 months after gamma knife radiosurgery at the authors' institution (eight cases) or elsewhere (two cases) revealed that six AVMs had not been covered completely by the prescribed isodose. Six (5%) of the 121 patients developed neurological deficits as a direct result of radiosurgical treatment. The authors infer from these data that malformations up to 30 cm3 in volume (approximately 4.0 cm in average diameter) can be treated effectively with an acceptably low complication rate using a radiosurgical dose of 16 Gy to the margin of the nidus. The obliteration rate for the larger malformations that were treated with a dose of 16 to 18 Gy appears to be similar to that for smaller ones treated with 18 to 20 Gy. As more experience accrues using radiosurgery to treat AVMs, patient selection criteria and the variables associated with successful obliteration of the nidus should become more clearly defined.     

Vitamin E modulation of dieldrin-induced hepatic focal lesion growth in mice

The purposes of this study were to determine the safety and efficacy of embolization of brain AVMs prior to radiosurgery and to evaluate the total obliteration rate achieved. The brain AVMs of 64 patients were subselectively embolized mainly with NBCA, platinum microcoils and/or PVA. The aim of embolization was the reduction of the target volume and/or the elimination of vascular structures bearing an increased risk of hemorrhage. Presenting symptoms were intracranial hemorrhage in 33 patients, a seizure disorder in 21 patients, and headache in 6 patients. Four AVMs had been detected as an incidental finding. The initial AVM volume was in the range of 0.5 to 84 cc (mean 17 cc). Grading of the AVMs according to the Spetzler-Martin scale showed the following distribution: grade I, 3x; II, 13x; III, 11x; IV, 17x; V, 4x; VI, 16x. A total of 300 endovascular procedures including 47 subselective catheterizations without and 253 with embolization were performed. A size reduction of the AVMs between 10% and 95% (mean 63%, median 70%) was achieved. Neurological symptoms due to treatment complications were transient in 12 patients, of minor clinical significance but permanent in 4 patients. Following radiosurgery, one patient died due to recurrent intracerebral hemorrhage. Three patients are doing well but refused final follow-up angiography. A total of 30 patients is currently within the latency interval after radiosurgery. Radiosurgery failed to obliterate the embolized AVMs in 16 patients. Angiography confirmed complete nidus obliteration in 14 patients. The endovascular treatment of brain AVMs prior to radiosurgery proved safe and effective and may be considered in either high grade or incidental AVMs. AVM obliteration after embolization and radiosurgery is less frequently achieved than after stereotactic irradiation of primarily small AVMs.     

Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience

OBJECTIVE: Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment. METHODS: All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr). RESULTS: Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery). CONCLUSION: Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.     

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty

PURPOSE: Radiosurgery is an effective treatment for cerebral arteriovenous malformations. We conducted the present study to investigate the feasibility and efficacy of gamma knife radiosurgery for dural arteriovenous fistulas (DAVFs) of the cavernous sinus. METHODS: Eighteen patients (12 women and six men; 29-75 years old [mean age, 55 years]) with DAVFs of the cavernous sinus (Barrow's type B:1, C:7, and D:10) treated by gamma knife radiosurgery were enrolled in the study. DAVFs were bilateral in six patients and unilateral in 12. Stereotactic X-ray angiography and MR imaging were performed for targeting the radiosurgery. Areas of arteriovenous communication targeted for irradiation were first outlined on the X-ray angiograms. The target regions were then transferred to and displayed on the MR images. Dose planning was based on findings on the integrated images. Prescribed maximum target doses were 22 to 38 Gy (mean, 28 Gy). The targets were covered by 50% to 90% isodose levels. Radiation doses to the surrounding optic apparatus were kept to less than 8 Gy. The patients were followed up with color Doppler sonography and MR imaging. When noninvasive imaging suggested obliteration, X-ray angiography was performed to verify the results. RESULTS: The DAVFs were totally obliterated in 12 (80%) of the 15 patients. In the other three, one was almost completely obliterated at 14 months and two were partially obliterated at 19 and 27 months, respectively, after radiosurgery. No complications or symptom worsening occurred during the follow-up period. CONCLUSION: Gamma knife radiosurgery is a feasible, effective, and safe treatment for DAVFs of the cavernous sinus. Integration of stereotactic X-ray angiography and MR imaging not only aids treatment efficacy but also protects the relevant vital structures, especially the optic apparatus, from the hazards of radiation.     

Pathological changes in surgically resected angiographically occult vascular malformations after radiation

OBJECTIVE: The goal of this study was to evaluate the pathological changes associated with radiation treatment (stereotactic radiosurgery or conventional irradiation) of angiographically occult vascular malformations (AOVMs). METHODS: Eleven patients underwent surgical resection of an AOVM in the mesial temporal lobe, brain stem, thalamus, or basal ganglia after previous radiation treatment. The indications for surgery were recurrent symptomatic bleeding from the lesion in 10 patients and recurrent intractable seizures in 1 patient. Radiation was used as the initial therapy because the risk of surgical resection was deemed too high. Three patients received conventional radiation therapy of 3000 to 5400 rads at an outside institution. One patient received radiosurgery with the gamma knife at another institution using a dose of 15 Gy to the margin. The remaining 7 patients received stereotactic radiosurgery with a helium-ion particle beam. The dose range was from 18 to 26 Gy equivalents. The interval from radiation to surgical resection ranged from 1 to 10 years, with a mean of 3.5 years. These lesions were compared with 10 nonirradiated cavernous malformations. RESULTS: One irradiated lesion was identified pathologically as a true arteriovenous malformation despite being angiographically occult. This lesion did not demonstrate significant changes in the vasculature but did have radiation necrosis of the surrounding brain 5 years after 25 Gy equivalents of helium-ion radiosurgery. Two other specimens were too small to identify the type of vascular malformation adequately. Of the remaining eight malformations identified as cavernous malformations, six showed a combination of marked fibrosis of the vascular channels, fibrinoid necrosis, and ferrugination. However, the fibrinoid necrosis was the only finding unique to the irradiated lesions compared with nonirradiated controls. All the irradiated lesions still had patent vascular channels; none were completely thrombosed. CONCLUSION: Radiosurgery or conventional radiation therapy did not cause histologic vascular obliteration in intracranial AOVMs evaluated 1 to 10 years (mean 3.5 yr) after radiation delivery. It should be recognized that these patients are irradiation failures who may not be representative of all irradiated patients. However, recurrent bleeding from AOVMs may relate to poor radiation response in some patients.     

Factors associated with successful arteriovenous malformation radiosurgery

OBJECTIVE: To analyze the clinical and angiographic variables that affect the results of arteriovenous malformation (AVM) radiosurgery and to propose a new method of reporting patient outcomes after AVM radiosurgery. This method incorporates both the obliteration status of the AVMs and the postoperative neurological condition of the patient. METHODS: Patient outcomes were defined as excellent (nidus obliteration and no new deficits), good (nidus obliteration with a new minor deficit), fair (nidus obliteration with a new major deficit), unchanged (incomplete nidus obliteration without a new deficit), poor (incomplete nidus obliteration with any new deficit), and dead. Two hundred twenty patients who underwent AVM radiosurgery at our center before 1992 were subjected to a multivariate analysis with patient outcomes as the dependent variable. RESULTS: Multivariate analysis determined four factors associated with successful AVM radiosurgery: smaller AVM volume (P=0.003), number of draining veins (P=0.001), younger patient age (P=0.0003), and hemispheric AVM location (P=0.002). Preradiosurgical embolization was a negative predictor of successful AVM radiosurgery (P=0.02). CONCLUSION: AVM obliteration without new neurological deficits can be achieved in at least 80% of patients with small volume, hemispheric AVMs after single-session AVM radiosurgery. Future studies on AVM radiosurgery should report patient outcomes in a fashion that incorporates all the factors involved in successful AVM radiosurgery.     

Trends in surgical management of astrocytomas and other brain gliomas

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.     

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.     

Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases

PURPOSE: Evaluation of the treatment outcome after radiosurgery (RS) alone or in combination with whole-brain radiotherapy (WBRT) with special attention to prescribed dose and its influence on local control and survival. PATIENTS AND METHODS: Between September 1984 and January 1997, 236 patients with 311 brain metastases treated with radiosurgery met the following inclusion criteria: one to three brain metastases per patient; no previous WBRT; and Kamofsky performance status (KPS) > or = 50%. One hundred fifty-eight patients treated only with RS received a median dose of 20 Gy prescribed to the 80% isodose line; 78 patients received RS with a median dose of 15 Gy/80% and an additional course of WBRT. RESULTS: For the entire series, overall median survival was 5.5 months, with control of CNS disease achieved in 92% of the treated brain metastases; the results were not significantly different between patients treated by RS with or without WBRT. However, in patients without evidence of extracranial disease, median survival was increased for patients who received WBRT (15.4 vs 8.3 months; P=.08). Additionally, there was a suggestion that increased doses for patients treated with RS only resulted in improved outcome. Four lesions were suspicious for radiation necrosis by magnetic resonance imaging (MRI); in one of the four lesions, radiation necrosis was confirmed histologically. The incidence of transient low-grade toxicity was 18%; symptoms could be treated by the temporary administration of steroids. CONCLUSION: RS is an effective, noninvasive means of controlling brain metastases when used alone or in combination with WBRT. There is a trend for superior local control and especially in patients without extracranial disease for superior survival when RS is used in conjunction with WBRT. Randomized trials would seem to be warranted, comparing the benefit of RS with or without additional WBRT.     

Effects of gamma knife radiosurgery for brain tumors: clinical evaluation

BACKGROUND: Gamma knife radiosurgery is a safe and effective alternative to microsurgery in the management of selected intracranial lesions. In our initial three-year experience with gamma knife radiosurgery, 431 patients were treated using this method. This report presents the treatment results for three different types of brain tumors: benign meningiomas, malignant metastases and gliomas. METHODS: A retrospective study was performed to analyze a consecutive series of 71 meningiomas, 31 metastatic tumors and 21 gliomas treated by gamma knife radiosurgery between March 1993 and May 1996. The treatment results were investigated using regular magnetic resonance examinations and tumor volume measurement at six-month intervals to observe sequential changes of the tumors. Patients with meningiomas were further divided into three groups according to the peripheral radiation doses: high-dose (20-17 Gy, n = 18), medium-dose (16-15 Gy, n = 33) and low-dose (14-12 Gy, n = 20). The Generalized Estimation Equation was applied to compare treatment results in these three groups with different doses and tumor volumes. RESULTS: Volume measurements of the 71 meningiomas showed that 76% decreased in size, 16% stabilized and 8% increased in size. The volumes increased most frequently in the early stage (6-12 months) after treatment and subsequently regressed after the twelfth month. The tumor control rate for meningiomas in our three-year follow-up was over 90%. For meningiomas, the statistical analysis showed that both the radiation dose and tumor volume were significantly related to the development of adverse radiation effects (p < 0.05). In metastatic tumors, rapid tumor regression after radiosurgery was found in 87% of the patients. In gliomas, radiosurgery effectively inhibited tumor growth in selected patients with small, circumscribed, less infiltrative tumors. Ependymomas and low-grade astrocytomas had more favorable outcomes than other gliomas. CONCLUSIONS: Gamma knife radiosurgery is effective for controlling tumor growth in benign meningiomas for up to three years after surgery. In selected cases of malignant metastasis and gliomas, most patients appeared to benefit from the treatment with symptomatic improvement and prolonged survival. Treatment strategy and dose selection in radiosurgery should be adjusted to optimize tumor control and avoid adverse radiation effects.     

Radiation optic neuropathy after stereotactic radiosurgery

PURPOSE: The purpose of the study is to report the occurrence of optic neuropathy after stereotactic radiosurgery for perichiasmal tumors. METHODS: Records of four patients with visual deterioration after stereotactic radiosurgery were reviewed, including clinical findings, neuroimaging results, and treatment methods. RESULTS: Optic neuropathy developed 7 to 30 months after gamma knife radiosurgery. All patients experienced an abrupt change in visual function. Clinical findings indicated anterior visual pathway involvement. Patterns of field loss included nerve fiber bundle and homonymous hemianopic defects. Gadolinium-enhanced magnetic resonance imaging (MRI) showed swelling and enhancement of the affected portion of the visual apparatus in three patients. Systemic corticosteroids were administered in all patients and one partially recovered. One patient also received hyperbaric oxygen without improvement. CONCLUSIONS: Although rare, optic neuropathy may follow radiosurgery to lesions near the visual pathways. Careful dose planning guided by MRI with restriction of the maximal dose to the visual pathways to less than 8 Gy will likely reduce the incidence of this complication.     

Reflections on the management of cerebral arteriovenous malformations

BACKGROUND: The authors report their personal experience in the management of cerebral arteriovenous malformations (AVMs), using the three techniques now available: surgical resection, endovascular embolization, and radiosurgery. They review the recent literature on this topic and present their current management algorithm based on this experience. METHODS: A series of 90 patients treated for cerebral AVMs is reported (68% Grade I-III and 32% Grade IV-V, Spetzler scale). The three methods of treatment were used, either individually or in combination, based on the size and the location of the malformation. The first intervention was surgical resection in 26% of cases, endovascular embolization in 57%, and radiosurgery in 17%. Surgery and embolization were followed by another technique in some cases and eventually single modality treatment was used in 58% of cases (surgical resection 21%, endovascular embolization 20%, radiosurgery 17%) and multimodality treatment in 42% (embolization + resection, 21%; embolization + radiosurgery, 17%; resection + radiosurgery, 4%). Embolization was used as reductive therapy in 38% of the overall series (65% of all embolized patients), and was followed by surgery in 56% of cases or by radiosurgery in 44%. Angiography was used to assess the cure rates. RESULTS: The following cure rates were obtained, when each technique was used as a first treatment: surgical resection, 82%; embolization, 6%; and radiosurgery, 83% (2-year angiographic follow-up). After combined treatment, embolization and resection resulted in a 100% cure rate, embolization and radiosurgery produced a 90% cure rate. The clinical outcome was evaluated in terms of deterioration attributable to treatment. Seventy-one percent of patients had no complication, minor complications were observed in 18%, and severe complications in 11%. Treatment mortality was 3%. All deaths were attributable to hemorrhage during the embolization procedure. CONCLUSIONS: In this management algorithm, AVMs submitted directly to surgery or to radiosurgery were considered "good risk" malformations, and the outcome for these cases was good in terms of clinical result and cure rate. AVMs submitted first to endovascular embolization were considered "poor risk" malformations, including a majority of Spetzler Grade IV-V lesions. Not surprisingly, the majority of severe complications occured in this group during embolization. Thus, the major risk of the treatment of AVMs has now shifted from surgery to endovascular techniques. Endovascular embolization as sole treatment gave a low rate of complete occlusion, but proved to be very useful as a reductive therapy, in preparation for further surgery or radiosurgery. Partial embolization permitted high rates of complete cure in difficult AVMs. Embolization should be used to the maximum extent possible as a reductive technique, despite the risks of the procedure. Because of its risks however, this technique of reductive embolization should be used only if absolutely necessary to allow the complete cure of the malformation. Thus, the use of embolization should be considered very cautiously in small malformations as well as in very large and complex AVMs in which partial embolization will not be sufficient to allow complete cure with either endovascular or surgical techniques.     

MR imaging in the evaluation of the therapeutic effect of B-RTO for gastric varices

BACKGROUNDS/AIMS: Balloon-occluded retrograde transvenous obliteration (B-RTO) has become a new treatment option for gastric varices. In the present study, mid-term follow-up data after B-RTO were presented, and the role of magnetic resonance imaging (MRI) and MR-portography in the assessment of therapeutic effect was evaluated. METHODOLOGY: Twelve patients with gastric varices were treated with up to three sessions of B-RTO. The patients were followed up with MRI, MR-portography, and endoscopy for a mean of 12.3 months. RESULTS: In ten patients, one (n = 8) or two (n = 2) sessions of B-RTO were effective to produce immediate (< 2 weeks) variceal obliteration on MRI and MR-portography. Endoscopic confirmation of variceal eradication was obtained within three (n = 9) or six (n = 1) months after B-RTO in these patients. The remaining two patients who underwent three sessions of B-RTO showed only a significant reduction in variceal size immediately after B-RTO, but variceal obliteration was observed within three months with subsequent variceal eradication. There were no signs of exacerbation of gastric varices on MRI and endoscopy in any patient during the follow-up period. CONCLUSIONS: The results suggest that B-RTO is effective for the treatment of gastric varices. MRI and MR-portography may provide accurate assessment of therapeutic effect.     

Value of repeat angiography in patients with spontaneous subcortical hemorrhage

BACKGROUND and PURPOSE: Neuroradiological investigations do not disclose a source of bleeding in some patients with spontaneous subcortical hemorrhage. These patients may harbor undetected vascular malformations and may be at risk of rebleeding in the future. We investigated patients with subcortical hemorrhage with use of repeat angiography and MRI to determine the incidence of occult vascular malformations and the risk of bleeding during follow-up. METHODS: We reviewed a consecutive series of 137 patients with subcortical hemorrhage during a 10-year period (June 1987 through June 1997). If the patient was <65 years old and the first angiogram and/or MRI did not show a source of bleeding, repeat angiography was recommended. All angiographic and MRI studies were reviewed. The relationship between the identified bleeding source and clinical variables such as patient age, sex, and history of hypertension and the size and location of the hematoma were examined. RESULTS: One hundred seven patients (78%) underwent angiography on admission, 10 (7%) had immediate surgery for hematoma without angiography, and 20 (15%) had neither angiography nor surgery. Overall, an etiology for the hemorrhage was found in 55 cases (40%). Vascular malformations were common in young patients without preexisting hypertension. A second angiogram was obtained in 22 patients, and 4 arteriovenous malformations were demonstrated. Rebleeding at the site of the initial hemorrhage was not observed after a mean follow-up of 68 months. CONCLUSIONS: Angiography performed acutely after hemorrhage may not demonstrate vascular malformations. Consideration should be given to repeat angiography in patients who do not have a specific cause for hemorrhage.     

Stability of chromatin in a cell-free system of Drosophila embryos

OBJECT: Certain patients, for example, elderly high-risk surgical patients, may be unfit for radiofrequency thalamotomy to treat parkinsonian tremor. Some patients, when given the opportunity, may choose to avoid an invasive surgical procedure. The authors retrospectively reviewed their experience using gamma knife radiosurgery for thalamotomies in this patient subpopulation: 1) to determine the efficacy of the procedure; 2) to see if there is a dose-response relationship; 3) to review radiological findings of radiosurgical lesioning; and 4) to assess the risks of complications. METHODS: Radiosurgical nucleus ventralis intermedius thalamotomy using the gamma knife unit was performed to make 38 lesions in 24 men and 10 women (median age 73 years, range 58-87 years) over a 5-year period. A median radiation dose of 130 Gy (range 100-165 Gy) was delivered to 38 nuclei (four patients underwent bilateral thalamotomy) using a single 4-mm collimator following classic anatomical landmarks. Twenty-nine lesions were made in the left nucleus ventralis intermedius thalamus for right-sided tremor. Patients were followed for a median of 28 months (range 6-58 months). Independent neurological evaluation of tremor based on the change in the Unified Parkinson's Disease Rating Scale tremor score was correlated with subjective patient evaluation. Comparison was made between a subgroup of patients in whom "low-dose" lesions were made (range 110-135 Gy, mean 120 Gy) and those in whom "high-dose" lesions were made (range 140-165 Gy, mean 160 Gy) for purposes of dose-response information. Four thalamotomies (10.5%) failed, four (10.5%) produced mild improvement, 11 (29%) produced good improvement, and 10 (26%) produced excellent relief of tremor. In nine thalamotomies (24%) the tremor was eliminated completely. The median time to onset of improvement was 2 months (range 1 week-8 months). Concordance between an independent neurologist's evaluation and that of the patient was statistically significant (p < 0.001). Two patients who underwent unilateral thalamotomy experienced bilateral improvement in their tremor. There were no neurological complications. There was better tremor reduction in the high-dose group than in the low-dose group (p < 0.04). CONCLUSIONS: Although less effective than other stereotactic techniques, gamma knife radiosurgery for thalamotomy offers tremor control with minimal risk to patients unsuited for open surgery.     

Stereotactic radiosurgery for tentorial meningiomas

Radical microsurgical resection is the procedure of choice for tentorial meningiomas. Despite advances in microsurgery, tentorial meningiomas continue to challenge surgeons and patients. To evaluate the response of tentorial meningiomas, we evaluated 41 patients who had Gamma knife stereotactic radiosurgery during a 9 year period. Patient age varied from 32 to 79 years. Headache, trigeminal neuralgia, or facial paraesthesia were the most common presenting symptoms. Sensory deficits in the distribution of the trigeminal nerve were the most common finding. Eighteen patients (44%) had undergone between 1 and 5 (mean, 1.9) resections prior to radiosurgery; 23 had tumors diagnosed by neuroimaging. The average tumor diameter in this series was 20 mm. The maximum tumor dose varied from 24 to 40 Gy (mean, 30.5 Gy), and the tumor margin dose varied from 12 to 20 Gy (mean, 15.3 Gy). During the average follow-up interval of 3 years (range, 1-8 years), 19 patients had clinical improvement, 20 remained stable, and 2 patients deteriorated. Follow-up imaging showed a reduction in tumor size in 18 patients, no further tumor growth in 22, and an increase in tumor size in one (overall tumor control rate of 98%). Stereotactic radiosurgery using the Gamma Knife was a safe and effective primary or adjuvant treatment for patients with tentorial meningiomas.     

Diagnostic and surgical management of spinal dural arteriovenous fistulas

OBJECTIVE: A retrospective review was conducted to compare magnetic resonance (MR) and conventional spinal angiographic images and to investigate the outcome of our treatment protocol for patients with spinal dural arteriovenous fistulas (DAVFs). MATERIALS AND METHODS: Nine patients with a diagnosis of DAVF based on clinical myelopathy and preoperative MR imaging (MRI) and MR angiography (MRA) findings were treated at our institution by the senior author (BAG). All nine patients initially presented with progressive myelopathy. Preoperative MRI revealed T2-weighted signal abnormalities in all patients, and MRA was diagnostic in all patients. Each patient underwent a laminectomy and ligation of the arterialized draining vein. Selective spinal angiograms were used to confirm the level of fistula immediately before the surgical procedure was performed and to document complete obliteration after clip ligation of the medullary draining vein. Follow-up MRI and MRA were performed approximately 2 months postoperatively. RESULTS: MRI T2-weighted signal hyperintensity improved after surgery in all nine patients. Postoperatively, progression of motor weakness and gait difficulty was halted and some improvement was observed in all patients. No patient was neurologically normal, however. To date, there has been no clinical or MRA evidence of recurrence in any patient. CONCLUSION: Preoperative MRA and intraoperative spinal x-ray angiography present as an effective combination for diagnosing and intraoperatively confirming DAVF. Both T1-weighted enhancement and T2-weighted signal hyperintensity on MR images improved after the obliteration of the DAVFs and correlated with clinical improvement in all nine patients. MRA provides adequate visualization and localization of spinal DAVFs and may serve as a useful noninvasive tool for diagnosing and following patients with spinal DAVFs in the future.     

Comparison of parental and health care professional preferences for the acellular or whole cell pertussis vaccine

PURPOSE: To evaluate the efficacy and toxicity of gamma knife radiosurgery in the treatment of melanoma metastases to the brain. PATIENTS AND METHODS: We retrospectively reviewed 55 patients with single or multiple intracranial melanoma metastases treated at the University of California, San Francisco, with gamma knife radiosurgery from 1991 through 1995. Sixteen patients were treated with gamma knife radiosurgery for recurrence following previous radiation therapy, 11 received radiosurgery as a boost to whole-brain radiation therapy, and 28 had radiosurgery alone for initial management of brain metastases. The median minimum radiosurgery tumor dose for 140 treated lesions was 19 Gy (range, 10-22 Gy) prescribed at the 35% to 90% isodose contour (median, 50%). The median total target volume per patient was 6.1 cc (range, 0.25-28.3 cc). RESULTS: With a median follow-up of 75 weeks in living patients, the median survival times were 35 weeks overall: 35 weeks for patients with solitary metastases versus 33 weeks for those with multiple metastases. A factor that was significant in univariate analysis of survival was total target volume treated. This parameter remained significant on multivariate analysis. The actuarial median freedom from progression analyzed by lesion for 113 lesions in 46 patients with imaging follow-up was 89 weeks with 6-month and 1-year actuarial freedom from progression rates of 89% (95% confidence interval, 80%-95%) and 77% (95% confidence interval, 62%-87%). In univariate analysis, improved freedom from progression was associated with smaller target volume treated, smaller maximum diameter, or higher prescribed dose. Four patients (7%) developed acute Radiation Therapy Oncology Group grade > or = 2 morbidity, and five patients (9%) developed late grade > or = 2 morbidity. DISCUSSION: Median survival and freedom from progression in patients treated with radiosurgery for melanoma metastatic to the brain are comparable to results in published radiosurgery series of grouped histologies. For melanoma patients, total intracranial tumor volume appears to be of greater prognostic significance than the absolute number of metastases treated. We conclude that gamma knife radiosurgery is effective and should be considered among various management strategies.     

Follow-up after patch aortoplasty for coarctation of aorta

BACKGROUND: Patch aortoplasty (PA) for coarctation of aorta (COA) can lead to aneurysm formation at the repair site. X-ray, echocardiogram and computed tomography are unreliable for diagnosis of this complication. OBJECTIVE: To evaluate prospectively patients with PA for COA by magnetic resonance imaging (MRI) to detect presence of aneurysm at the repair site. DESIGN: All patients who underwent PA at the authors' institution were identified. MRI was performed in transverse and long axis oblique views on all patients except those who had, or were going to have, aortic angiography for other reasons. Details of the surgical procedure were obtained from the hospital records. RESULTS: Of the 18 patients studied, 15 had MRI and three had aortic angiography. Age at PA ranged from one week to 13.3 years (mean 6.3 years). The interval from PA to MRI or angiography was 9.5 years (range four to 12.5). No aneurysm was detected in any patient. Recoarctation was diagnosed in two patients not previously suspected but discovered on MRI. At PA the intimal shelf causing coarctation was either not excised or only minimally trimmed in 14 of 15 instances. CONCLUSIONS: The incidence of late aneurysm formation following PA for COA is low in the authors' patients, possibly due to minimal intimal damage at repair, although these patients should be followed longer. MRI was useful for assessment of aneurysm and restenosis.     

Risk of recurrent subarachnoid hemorrhage after complete obliteration of cerebral aneurysms

BACKGROUND and PURPOSE: The neck clipping of cerebral aneurysms is a well-established treatment for subarachnoid hemorrhage (SAH) caused by aneurysmal rupture. However, it is still unclear how great a risk of recurrence patients with a successfully treated aneurysm carry over a long-term period. METHODS: Of 425 patients with SAH surgically treated in Aizu Chuou Hospital from 1976 to 1994, 220 cases meeting the following criteria were studied: (1) all aneurysms detected by 3- or 4-vessel cerebral angiography were clipped, (2) complete obliteration of aneurysm(s) was confirmed by postoperative angiography, and (3) the patient survived >3 years. All patients were traced until January 1998 for recurrent SAH or death. The mean follow-up period was 9.9 (range, 3 to 21) years. RESULTS: Six patients (2.7%) had recurrent SAH, each with an interval ranging from 3 to 17 years (mean, 11 years) since the original treatment. In addition, 2 patients were found to have regrowth of the originally operated aneurysms. The cumulative recurrence rate of SAH, calculated using the Kaplan-Meier method, was 2.2% at 10 years and 9. 0% at 20 years after the original treatment. CONCLUSIONS: The recurrence rate was considerably higher than the previously reported risk of SAH in the normal population, and the rate increased with time. These data indicate that patients with ruptured cerebral aneurysms still carry higher risks for SAH in a long-term period, even after complete obliteration of the aneurysm, and that periodic examination to detect recurrent aneurysms may be indicated for such patients.