The nucleus accumbens as a potential target for central poststroke pain.

Although deep brain stimulation (DBS) has been found to be efficacious for some chronic pain syndromes, its usefulness in patients with central poststroke pain (CPSP) has been disappointing. The most common DBS targets for pain are the periventricular gray region (PVG) and the ventralis caudalis of the thalamus. Despite the limited success of DBS for CPSP, few alternative targets have been explored. The nucleus accumbens (NAC), a limbic structure within the ventral striatum that is involved in reward and pain processing, has emerged as an effective target for psychiatric disease. There is also evidence that it may be an effective target for pain. We describe a 72-year-old woman with a large right hemisphere infarct who subsequently experienced refractory left hemibody pain. She underwent placement of 3 electrodes in the right PVG, ventralis caudalis of the thalamus, and NAC. Individual stimulation of the NAC and PVG provided substantial improvement in pain rating. The patient underwent implantation of permanent electrodes in both targets, and combined stimulation has provided sustained pain relief at nearly 1 year after the procedure. These results suggest that the NAC may be an effective DBS target for CPSP.

Stereotactic radiosurgery for patients with "radioresistant" brain metastases.

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.

Patient outcomes after vestibular schwannoma management: a prospective comparison of microsurgical resection and stereotactic radiosurgery.

OBJECTIVE: The best management for patients with small- to medium-sized vestibular schwannomas (VS) is controversial. METHODS: : A prospective cohort study of 82 patients with unilateral, unoperated VS less than 3 cm undergoing surgical resection (n = 36) or radiosurgery (n = 46). Patients undergoing resection were younger (48.2 yr versus 53.9 yr, P = 0.03). The groups were similar with regard to hearing loss, associated symptoms, and tumor size. The mean follow-up period was 42 months (range, 12-62 mo). RESULTS: Normal facial movement and preservation of serviceable hearing was more frequent in the radiosurgical group at 3 months (P < 0.001), 1 year (P < 0.001), and at the last follow-up examination (P < 0.01) compared with the surgical resection group. Patients undergoing surgical resection had a significant decline in the following subscales of the Health Status Questionnaire 3 months after surgery: physical functioning (P = 0.006), role-physical (P < 0.001), energy/fatigue (P = 0.02), and overall physical component (P = 0.004). Patients in the surgical resection group continued to have a significant decline in the physical functioning (P = 0.04) and bodily pain (P = 0.04) subscales at 1 year and in bodily pain (P = 0.02) at the last follow-up examination. The radiosurgical group had no decline on any component of the Health Status Questionnaire after the procedure. The radiosurgical group had lower mean Dizziness Handicap Inventory scores (16.5 versus 8.4, P = 0.02) at the last follow-up examination. There was no difference in tumor control (100 versus 96%, P = 0.50). CONCLUSION: Early outcomes were better for VS patients undergoing stereotactic radiosurgery compared with surgical resection (Level 2 evidence). Unless long-term follow-up evaluation shows frequent tumor progression at currently used radiation doses, radiosurgery should be considered the best management strategy for the majority of VS patients.

Gamma knife radiosurgery of radiation-induced intracranial tumors: local control, outcomes, and complications.

PURPOSE: To determine local control (LC) and complication rates for patients who underwent radiosurgery for radiation-induced intracranial tumors. METHODS AND MATERIALS: Review of a prospectively maintained database (2,714 patients) identified 16 patients (20 tumors) with radiation-induced tumors treated with radiosurgery between 1990 and 2004. Tumor types included typical meningioma (n=17), atypical meningioma (n=2), and schwannoma (n=1). Median patient age at radiosurgery was 47.5 years (range, 27-70 years). The median tumor margin dose was 16 Gy (range, 12-20 Gy). Median follow-up was 40.2 months (range, 10.8-146.2 months). Time-to-event outcomes were calculated with Kaplan-Meier estimates. RESULTS: Three-year and 5-year LC rates were 100%. Three-year and 5-year overall survival rates were 92% and 80%, respectively. Cause-specific survival rates at 3 and 5 years were 100%. Three patients died: 1 had in-field progression 65.1 months after radiosurgery and later died of the tumor, 1 died of progression of a preexisting brain malignancy, and 1 died of an unrelated cause. One patient had increased seizure activity that correlated with development of edema seen on neuroimaging. CONCLUSIONS: LC, survival, and complication rates in our series are comparable to those in previous reports of radiosurgery for intracranial meningiomas. Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas. Radiosurgery is a safe and effective treatment option for radiation-induced intracranial tumors, most of which are typical meningiomas.

Radiosurgery for arteriovenous malformations of the basal ganglia, thalamus, and brainstem.

OBJECT: Although stereotactic radiosurgery is frequently performed for arteriovenous malformations (AVMs) in deep locations, outcomes after radiosurgery for these patients have not been well studied. The goal of this paper was to study these outcomes. METHODS: Between 1990 and 2000, 56 patients underwent radiosurgery for AVMs located in the basal ganglia (10 patients), thalamus (30 patients), or brainstem (16 patients). The median age of these patients was 34.2 years. Thirty-five patients (62%) had experienced previous bleeding. The AVMs were classified Grade IIIB in 62% of patients and Grade IV in 38% according to the modified Spetzler-Martin Scale; the median radiosurgery-based AVM score was 1.83. The median volume of the lesion was 3.8 cm3 and the median radiation dose delivered to its margin was 18 Gy. The median duration of follow-up review after radiosurgery was 45 months (range 3-121 months). In seven patients (12%) hemorrhage occurred at a median of 12 months after radiosurgery; five patients (9%) died and two recovered without any deficit. Permanent radiation-related complications occurred in six (12%) of 51 patients (excluding the five patients who died of hemorrhage) after one procedure and in three (18%) of 17 patients after repeated radiosurgery. Obliteration of the AVM was noted in 24 patients (43%; obliteration was confirmed by angiography in 18 patients and by magnetic resonance [MR] imaging in six patients) after a single procedure and in 32 patients (57%; confirmed by angiography in 25 patients and by MR imaging in seven patients) after one or more procedures. Excellent outcomes (obliteration of the lesion without any new deficit) were obtained in 39% of patients after one radiosurgical procedure and in 48% after one or more procedures. Twelve (67%) of 18 patients with AVM scores lower than 1.5 had excellent outcomes compared with 15 (39%) of 38 patients with AVM scores greater than 1.5 (p = 0.053). CONCLUSIONS: Less than half of the patients with deeply located AVMs were cured of the future risk of hemorrhage without new neurological deficits. This experience emphasizes the difficulty in treating patients with deeply located AVMs; the majority of whom are also poor candidates for resection or embolization.

Patient outcomes after arteriovenous malformation radiosurgical management: results based on a 5- to 14-year follow-up study.

OBJECTIVE: Radiosurgery is commonly performed for patients with small to medium-sized arteriovenous malformations (AVMs). However, few articles present overall outcomes after one or more radiosurgical procedures, and few data are available for periods longer than 5 years after AVM radiosurgery. METHODS: Between 1990 and 1997, 144 patients underwent AVM radiosurgery and had angiographic follow-up. Of these patients, 112 (78%) had Spetzler-Martin Grade III or greater AVMs; 37 (26%) were located in the basal ganglia, thalamus, or brainstem. Twenty-six patients (18%) underwent repeat radiosurgery. The mean follow-up of 15 patients who died as a result of AVM bleeding or underwent AVM resection after the initial radiosurgery was 22 months (range, 3-47 mo); the mean follow-up of the remaining 129 patients was 86 months (range, 23-169 mo). RESULTS: Excellent (obliteration without deficit, n = 96) or good (obliteration with minor deficit, n = 9) outcomes were achieved in 73% of patients after one or more radiosurgical procedures. Twenty patients (14%) sustained major deficits (n = 15; five had obliteration) or died (n = 5) after radiosurgery. Sixteen patients (11%) had unchanged neurological examinations but persistent arteriovenous shunting. Five patients (4%) required surgery (cystoperitoneal shunting, n = 1; AVM resection, n = 4) at a median of 65 months after radiosurgery because of symptomatic cyst formation or persistent edema. The radiosurgery AVM score correlated with both excellent (R(2) = -0.93, P = 0.003) and excellent or good (R(2) = -0.92, P = 0.004) outcomes. CONCLUSION: The majority of AVM patients are protected from the risk of future hemorrhage and continue their normal daily activities after radiosurgery. Late complications requiring treatment are rare but can occur many years after patients are considered cured of their AVMs. Overall outcomes after AVM radiosurgery seem to be predicted accurately by the described method.

A study on the radiation tolerance of the optic nerves and chiasm after stereotactic radiosurgery.

PURPOSE: To evaluate the risk of clinically significant radiation optic neuropathy (RON) for patients having stereotactic radiosurgery of benign tumors adjacent to the optic apparatus. METHODS AND MATERIALS: We reviewed the dose plans and clinical outcomes of 218 gamma knife procedures (215 patients) for tumors of the sellar and parasellar region (meningiomas, n = 122; pituitary adenomas, n = 89; craniopharyngiomas, n = 7 patients). Previous surgery or radiation therapy was performed in 156 (66%) and 24 (11%) patients, respectively. Median follow-up was 40 months (range 4-115). RESULTS: The median maximum radiation dose to the optic nerve was 10 Gy (range 0.4-16.0). Four patients (1.9%) developed RON at a median of 48 months after radiosurgery. All had prior surgery, and 3 of 4 had external beam radiotherapy (EBRT) in their management either before (n = 2) or adjuvantly (n = 1). The risk of developing a clinically significant RON was 1.1% for patients receiving 12 Gy or less. Patients receiving prior or concurrent EBRT had a greater risk of developing RON after radiosurgery (p = 0.004). CONCLUSION: RON occurred in less than 2% of our patients, despite the majority (73%) receiving more than 8 Gy to a short segment of the optic apparatus. Knowledge of the dose tolerance of these structures permits physicians to be more aggressive in treating patients with sellar or parasellar tumors, especially those with hormone-producing pituitary adenomas that appear to require higher doses to achieve biochemical remission.

Stereotactic radiosurgery for idiopathic trigeminal neuralgia.

OBJECT: Each year a greater number of patients with trigeminal neuralgia (TN) undergo radiosurgery, including a large number of patients who are candidates for microvascular decompression (MVD). METHODS: The case characteristics and outcomes of 117 consecutive patients who underwent radiosurgery were retrieved from a prospectively maintained database. The mean patient age was 67.8 years; and the majority (58%) of patients had undergone surgery previously. The dependent variable for all analyses of facial pain was complete pain relief without medication (excellent outcome). Median follow-up duration was 26 months (range 1-48 months). The actuarial rate of achieving and maintaining an excellent outcome was 57% and 55% at 1 and 3 years, respectively, after radiosurgery. A greater percentage of patients who had not previously undergone surgery achieved and maintained excellent outcomes (67% at 1 and 3 years) than that of patients who had undergone prior surgery (51% and 47% at 1 and 3 years, respectively; relative risk [RR] = 1.77, 95% confidence interval [CI] 1.01-3.13, p = 0.04). New persistent trigeminal dysfunction was noted in 43 patients (37%). Tolerable numbness or paresthesias occurred in 29 patients (25%), whereas bothersome dysesthesias developed in 14 patients (12%). Only a radiation dose of 90 Gy correlated with new trigeminal deficits or dysesthesias (RR = 3.10, 95% CI 1.64-5.81, p < 0.001). Excellent outcomes in patients with new trigeminal dysfunction were achieved and maintained at rates of 76% and 74% at 1 and 3 years, respectively, after radiosurgery, compared with respective rates of 46% and 42% in patients who did not experience postradiosurgery trigeminal dysfunction (RR = 4.53, 95% CI 2.03-9.95, p < 0.01). CONCLUSIONS: Radiosurgical treatment provides complete pain relief for the majority of patients with idiopathic TN. There is a strong correlation between the development of new facial sensory loss and achievement and maintenance of pain relief after this procedure. Because the long-term results of radiosurgery still remain unknown, MVD should continue to be the primary operation for medically fit patients with TN.

Stereotactic radiosurgery for patients with "radioresistant" brain metastases.

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.

Glomus jugulare tumor: tumor control and complications after stereotactic radiosurgery.

BACKGROUND: We evaluated toxicity and long-term efficacy of stereotactic radiosurgery in patients with symptomatic or progressive glomus jugulare tumors. METHODS: Twenty-five consecutive patients (age, 30-88 years; 17 women, 8 men) who underwent stereotactic radiosurgery with the Leksell Gamma Knife (dose, 12-18 Gy) were prospectively followed. MRI and clinical examinations were performed at 6 months and 1, 2, and 3 years, and then every 2 years. RESULTS: None of the tumors increased in size, 17 were stable, and 8 decreased (median imaging follow-up, 35 months; range, 10-113 months). Symptoms subsided in 15 patients (60%); vertigo occurred in 1, but balance improved with vestibular training (median clinical follow-up, 37 months; range, 11-118 months). No other new or progressive neuropathy of cranial nerves V-XII developed. CONCLUSIONS: Stereotactic radiosurgery can achieve excellent tumor control with low risk of morbidity in the treatment of glomus jugulare tumors. The lower cranial nerves can safely tolerate a radiosurgical dose of 12 to 18 Gy.

Evaluation of gamma knife radiosurgery in the treatment of oligodendrogliomas and mixed oligodendroastrocytomas.

OBJECT: Radiosurgery is commonly used for the treatment of patients with glioma. The goal of this study was to evaluate the safety and efficacy of radiosurgery in the management of patients with oligodendrogliomas (ODGs) or mixed oligoastrocytomas (OGAs). METHODS: A retrospective chart review of patients treated between May 1990 and January 2000 identified 18 patients (21 tumors) with either an ODG (10) or a mixed OGA (11) who had undergone radiosurgery. The median patient age was 43 years (range 23-67 years). Sixteen patients had undergone one or more tumor resections before radiosurgery; in two patients biopsy sampling alone had been performed. Tumor grades at the most recent operation were Grade I (one), Grade 2 (one), Grade 3 (12), and Grade 4 (seven patients). Seventeen patients had undergone prior radiotherapy; 11 were treated with chemotherapy before radiosurgery, and one had undergone a prior linear accelerator-based radiosurgery treatment. The median tumor volume was 8.2 cm3 (range 1.9-47.7 cm3); the median margin dose was 15 Gy (range 12-20 Gy); and the median maximum dose was 32 Gy (range 24-50 Gy). In this heterogeneous group, 12 patients died whereas six remain alive. Survival after radiosurgery was 78%, 61%, and 44% at 12, 24, and 48 months, respectively. Factors associated with an improved survival rate included younger age and smaller tumors. CONCLUSIONS: For patients with oligoastroglial tumors that have failed to respond to conventional therapies, radiosurgery may provide some survival benefit. Further study is needed to determine which subpopulation of these patients will have the best chances of enhanced survival from this treatment.