Sensitivity to radiation-induced apoptosis and neuron loss declines rapidly in the postnatal mouse neocortex.

Therapeutic brain irradiation can cause progressive decline in cognitive function, particularly in children, but the reason for this effect is unclear. The study explored whether age-related differences in apoptotic sensitivity might contribute to the increased vulnerability of the young brain to radiation. Postnatal day 1 (P1) to P30 mice were treated with 0-16 Gy whole-body X-irradiation. Apoptotic cells were identified and quantified up to 48 h later using the TdT-UTP nick end-labelling method (TUNEL) and immunohistochemistry for activated caspase-3. The number of neuron-specific nuclear protein (NeuN)-positive and -negative cells were also counted to measure neuronal and non-neuronal cell loss. Significantly greater TUNEL labelling occurred in the cortex of irradiated P1 animals relative to the other age groups, but there was no difference among the P7, P14 and P30 groups. Irradiation decreased the %NeuN-positive cells in the mice irradiated on P1, whereas in P14 animals, irradiation led to an increase in the %NeuN-positive cells. These data demonstrate that neocortical neurons of very young mice are more susceptible to radiation-induced apoptosis. However, this sensitivity decreases rapidly after birth. By P14, acute cell loss due to radiation occurs primarily in non-neuronal populations.

Radiosurgery for hemangioblastoma: results of a multiinstitutional experience.

PURPOSE: Between June 1988 and June 1994. 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection. METHODS AND MATERIALS: SR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy). RESULTS: Median follow-up from the time of SR was 24.5 months (range: 6-77 months). The 2-year actuarial over-all survival was 88 +/- 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 +/- 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20-10.53 cc) compared to 0.67 cc (range: 0.05-12 cc) for controlled lesions (p - 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13-17 Gy) compared to 16 Gy (range: 12-20 Gy) for controlled lesions (p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR. CONCLUSIONS: This report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.

The efficacy of particulate embolization combined with stereotactic radiosurgery for treatment of large arteriovenous malformations of the brain.

PURPOSE: To evaluate the efficacy of combined particulate embolization and single-stage stereotactic radiosurgery in the treatment of large arteriovenous malformations (AVMs) of the brain. METHODS: Twenty-four patients with large brain AVMs (diameter > 3.0 cm; volume > 14 cm3), who had previously undergone particulate embolization and stereotactic radiosurgery, were retrospectively evaluated 2 or more years after radiosurgery. RESULTS: In 12 (50%) of these patients there was complete AVM obliteration, comparing favorably with a 58% obliteration rate in a group of AVMs having a 4- to 10-cm3 volume, treated by radiosurgery alone. Recanalization of embolized, but not radiated, AVM segments was identified in 3 (12%) patients. However, long-term occlusion was demonstrated in the embolized portions of most AVMs subsequently treated by radiosurgery. Complications included 1 (4%) patient with a mild upper extremity paresis after radiosurgery and 2 (8%) patients with transient neurologic deficits after embolization. CONCLUSION: Combined embolization and stereotactic radiosurgery was more efficacious than radiosurgery alone for large brain AVMs. Recanalization after embolization did occur but was a relatively minor cause of treatment failure.

Cranial nerve preservation after stereotactic radiosurgery for small acoustic tumors.

OBJECTIVE: To assess those factors associated with and predictive of cranial nerve preservation after stereotactic radiosurgery in patients with small acoustic tumors identified by magnetic resonance imaging. DESIGN: We performed a retrospective analysis of our experience with 31 patients with preserved hearing and acoustic tumors measuring 10 mm or smaller (pons-to-petrous dimension). All patients underwent clinical and audiologic evaluations varying from 6 to 48 months (mean, 20 months) after stereotactic radiosurgery performed with use of the 201 source cobalt 60 gamma unit. RESULTS: Stabilization or reduction in tumor volume was achieved in 29 of 31 patients. One patient required delayed microsurgical resection. Useful hearing (pure tone average < or = 50 dB and speech discrimination score > or = 50%) preservation was achieved in 10 of 10 patients immediately postoperatively, eight of 10 patients at 6 months, six of 10 patients at 1 year, and five of 10 at 2 years. Preservation of some measurable hearing was possible in all patients immediately after radiosurgery, in 84% and in more than half of patients at 2 years. Preoperative facial nerve function was preserved in 19 of 20 patients at 2 years after radiosurgery. All patients returned to their preoperative employment status within 2 to 5 days after radiosurgery. CONCLUSION: Stereotactic radiosurgery performed with current technology (multiple radiation isocenters and magnetic resonance imaging guidance) is a safe and effective management strategy for patients with small acoustic tumors. The risk of facial and trigeminal neuropathy after gamma knife radiosurgery is low, and useful hearing can be preserved in up to 50% of patients with useful preoperative hearing. Stereotactic radiosurgery is a valuable alternative strategy to surgical removal for many patients with newly diagnosed small acoustic tumors.

Cranial nerve preservation after stereotactic radiosurgery of intracanalicular acoustic tumors.

We reviewed our initial stereotactic radiosurgery experience in 10 patients with intracanalicular acoustic tumors managed by radiosurgery during a 5-year period. These patients constitute 4.7% of acoustic tumor patients who underwent Gamma Knife radiosurgery during this period. Tumor volume stabilization was achieved in 8. Two patients had initial growth followed by delayed growth arrest. Preservation of preoperative hearing was achieved in all patients in the immediate postoperative period and in 8 of 10 at 1 year. No patient had developed facial or trigeminal nerve dysfunction at the last follow-up, which varied from 3 to 64 months (mean 25 months). Tumor growth was delayed in 2 patients, but neither has required delayed microsurgical resection. All patients returned to their preoperative functional status within 3-5 days after radiosurgery. Stereotactic radiosurgery using the Gamma Knife is a safe and effective management strategy for intracanalicular acoustic tumor patients. Our initial results indicate that high cranial nerve preservation rates and a rapid return to previous activity and employment are benefits of radiosurgery.

Comparison of functional magnetic resonance imaging with positron emission tomography and magnetoencephalography to identify the motor cortex in a patient with an arteriovenous malformation.

Alterations in gyral contour made it difficult to identify the motor cortex thought to be near an arteriovenous malformation (AVM) in a 24-year-old man considered for stereotactic radiosurgery. Functional imaging in three modalities was performed preoperatively to compare the reliability of localization using functional magnetic resonance imaging (fMRI) on a conventional scanner with positron emission tomography (PET) and magnetoencephalography (MEG). Similar tasks were used for each imaging modality in an attempt to activate and identify the sensory and motor cortex. Data from all three modalities converged for the sensory task, and fMRI and PET data converged for the motor task. The right hemisphere motor strip was localized adjacent and anterior to the AVM. These data were used in planning the radiosurgery isodose configuration to the AVM in order to reduce the irradiation of motor cortex parenchyma. A postoperative fMRI study was also performed using newer techniques to reduce head motion artifact and to improve signal-to-noise ratio. The data confirmed the conclusions derived from the preoperative evaluations. This study demonstrates how conventional MRI scanners can be used for functional studies of use in surgical planning.

Stereotactic options in the management of craniopharyngioma.

Multimodality stereotactic techniques were used in the management of 39 patients with craniopharyngiomas in a 12-year interval. Monocystic craniopharyngiomas were treated successfully by intracavitary beta-irradiation using 32P (96% cyst control rate). Solid tumor progression or secondary cyst formation required repeat irradiation, radiosurgery or microsurgery in selected patients. In the future, wider and earlier application of stereotactic techniques may further reduce the still unacceptable morbidity currently associated with initial radical microsurgical resection of craniopharyngiomas.