Frank J. Bova

Cognition and Mood in Parkinson's Disease in Subthalamic Nucleus versus Globus Pallidus Interna Deep Brain Stimulation: The COMPARE Trial

Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease.

Prophylactic glutamine protects the intestinal mucosa from radiation injury.

Glutamine may be an essential dietary component, especially for the support of intestinal mucosal growth and function. This study evaluated the effects of a glutamine‐enriched elemental diet, administered before whole‐abdominal radiation on gut glutamine metabolism, mucosal morphometrics, and bacterial translocation. Rats were randomized to receive a nutritionally complete elemental diet that was glutamine‐enriched or glutamine‐free for 4 days. The animals were then subjected to a single dose of 1000 cGy x‐radiation to the abdomen. After irradiation, all animals received the glutamine‐free diet. Four days later the animals underwent laparotomy for sampling of arterial and portal venous blood, culture of mesenteric lymph nodes, and removal of the small intestine for microscopic examination. There was no difference in arterial glutamine or gut glutamine extraction between the two groups, but body weight loss was significantly diminished in the glutamine‐fed rats. Rats receiving the glutamine‐enriched elemental diet before radiation had a significant increase in jejunal villous number, villous height, and number of metaphase mitoses per crypt. Scanning electron microscopy confirmed the presence of an intact gut epithelium in eight of eight rats receiving prophylactic glutamine compared to one of eight animals in the glutamine‐free group. Three of eight rats fed glutamine had culture positive mesenteric lymph nodes compared with five of seven rats receiving the glutamine‐free diet. Glutamine exerts a protective effect on the small bowel mucosa by supporting crypt cell proliferation which may accelerate healing of the acutely radiated bowel.

The University of Florida radiosurgery system

A new, linear accelerator based radiosurgical system has been designed and tested. It incorporates a mechanical system of precision bearings to control all patient and accelerator movements. The dosimetry system allows near real-time examination of the isodose distributions in any computed tomography plane such that any treatment plan can be quickly optimized. Extensive testing shows a radiation beam accuracy of .2 +/- .1 mm. The dose gradient between the 90% and 10% isodose distributions compares favorably with any previously published radiosurgical method.

RADIATION RETINOPATHY AFTER EXTERNAL-BEAM IRRADIATION: ANALYSIS OF TIME-DOSE FACTORS

PURPOSE To investigate the risk of radiation-induced retinopathy according to total radiation dose and fraction size, based on both retrospective and prospectively collected data. METHODS AND MATERIALS Between October 1964 and May 1989, 68 retinae in 64 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 26 years; mean, 9 years; median, 8 years). RESULTS Twenty-seven eyes in 26 patients developed radiation retinopathy resulting in visual acuity of 20/200 or worse. The mean and median times to the onset of symptoms attributable to retinal ischemia were 2.8 and 2.5 years, respectively. Fourteen of the injured eyes developed rubeosis iridis and/or neovascular glaucoma. Radiation retinopathy was not observed at doses below 45 Gy, but increased steadily in incidence at doses > or = 45 Gy. In the range of doses between 45 and 55 Gy, there was an increased risk of injury among patients who received doses per fraction of > or = 1.9 Gy (p = .09). There was also a trend toward increased risk of injury among patients who received chemotherapy (two of two vs. four of ten in the 45-51 Gy range; p = .23). The lowest dose associated with retinopathy was 45 Gy delivered to a diabetic patient by twice-a-day fractionation. The data did not suggest an increased risk of radiation retinopathy with increasing age. CONCLUSION The current study suggests the importance of total dose as well as dose per fraction, and adds support to a small body of literature suggesting that patients with diabetes mellitus or who receive chemotherapy are at increased risk of injury. A sigmoid dose-response curve is constructed from our current data and data from the literature.

Analysis of Factors Predictive of Success or Complications in Arteriovenous Malformation Radiosurgery

OBJECTIVEThis study was undertaken to determine which factors were statistically predictive of radiological and clinical outcomes in the radiosurgical treatment of arteriovenous malformations (AVMs). METHODSThe computerized dosimetric and clinical data for 269 patients were reviewed. The AVM nidus was hand-contoured on successive enhanced computed tomographic slices through the nidus, to allow detailed determinations of nidus volume, target miss, normal brain tissue treated, dose conformality, and dose gradient. In addition, a number of patient and treatment factors, including Spetzler-Martin grade, presenting symptoms, dose, number of isocenters, radiological outcome, and clinical outcome, were subjected to multivariate analysis. RESULTSTwo hundred twenty-five patients were treated with radiosurgery for the first time, and 44 patients underwent radiosurgical retreatment. One hundred forty-three patients had AVMs located in or near “eloquent” brain areas and 126 patients did not. Seventy patients demonstrated preoperative neurological findings related to the AVM and 199 did not. Twenty-six patients had previously undergone endovascular treatment and 10 patients had previously undergone surgical treatment of their AVMs. Of the 269 patients studied, 228 experienced no complication, 10 (3.7%) experienced a transient radiation-induced complication, 3 (1%) experienced a permanent radiation-induced complication, and 28 (10%) experienced posttreatment hemorrhage. CONCLUSIONNone of the analyzed factors was predictive of hemorrhage after radiosurgery in this study. The 12-Gy volume was predictive of permanent radiation-induced complications. Eloquent AVM location and 12-Gy volume were correlated with the occurrence of transient radiation-induced complications. Better conformality was correlated with a reduced incidence of transient complications. Lower Spetzler-Martin grades, higher doses, and steeper dose gradients were correlated with radiological success.

Severe dry-eye syndrome following external beam irradiation.

PURPOSE There are limited data in the literature on the probability of dry-eye complications according to radiotherapy dose. This study investigates the risk of radiation-induced severe dry-eye syndrome in patients in whom an entire orbit was exposed to fractionated external beam irradiation. METHODS AND MATERIALS Between October 1964 and May 1989, 33 patients with extracranial head and neck tumors received irradiation of an entire orbit. Most patients were treated with 60Co. The dose to the lacrimal apparatus was calculated at a depth of 1 cm from the anterior skin surface, the approximate depth of the major lacrimal gland. The end point of the study was severe dry-eye syndrome sufficient to produce visual loss secondary to corneal opacification, ulceration, or vascularization. RESULTS Twenty patients developed severe dry-eye syndrome. All 17 patients who received doses > or = 57 Gy developed severe dry-eye syndrome. Three (19%) of 16 patients who received doses < or = 45 Gy developed severe dry-eye syndrome; injuries in the latter group were much slower to develop (4 to 11 years) than in the higher dose group, in whom corneal vascularization and opacification were usually pronounced within 9-10 months. There were no data for the range of doses between 45.01 and 56.99 Gy. The data did not suggest an increased risk of severe dry-eye syndrome with increasing age. CONCLUSION Data from the current series and the literature are combined to construct a sigmoid dose response curve. The incidence of injury increases from 0% reported after doses < or = 30 Gy to 100% after doses > or = 57 Gy.

Image localization for frameless stereotactic radiotherapy

PURPOSE Infrared light-emitting diodes (IRLEDs) have been used for optic-guided stereotactic radiotherapy localization at the University of Florida since 1995. The current paradigm requires stereotactic head ring placement for the patients first fraction. The stereotactic coordinates and treatment plan are determined relative to this head ring. The IRLEDs are attached to the patient via a maxillary bite plate, and the position of the IRLEDs relative to linac isocenter is saved to file. These positions are then recalled for each subsequent treatment to position the patient for fractionated therapy. The purpose of this article was to report a method of predicting the desired IRLED locations without need for the invasive head ring. METHODS AND MATERIALS To achieve the goal of frameless optic-guided radiotherapy, a method is required for direct localization of the IRLED positions from a CT scan. Because it is difficult to localize the exact point of light emission from a CT scan of an IRLED, a new bite plate was designed that contains eight aluminum fiducial markers along with the six IRLEDs. After a calibration procedure to establish the spatial relationship of the IRLEDs to the aluminum fiducial markers, the stereotactic coordinates of the IRLED light emission points are determined by localizing the aluminum fiducial markers in a stereotactic CT scan. RESULTS To test the accuracy of direct CT determination of the IRLED positions, phantom tests were performed. The average accuracy of isocenter localization using the IRLED bite plate was 0.65 +/- 0. 17 mm for these phantom tests. In addition, the optic-guided system has a unique compatibility with the stereotactic head ring. Therefore, the isocentric localization capability was clinically tested using the stereotactic head ring as the absolute standard. The ongoing clinical trial has shown the frameless system to provide a patient localization accuracy of 1.11 +/- 0.3 mm compared with the head ring. CONCLUSION Optic-guided radiotherapy using IRLEDs provides a mechanism through which setup accuracy may be improved over conventional techniques. To date, this optic-guided therapy has been used only as a hybrid system that requires use of the stereotactic head ring for the first fraction. This has limited its use in the routine clinical setting. Computation of the desired IRLED positions eliminates the need for the invasive head ring for the first fraction. This allows application of optic-guided therapy to a larger cohort of patients, and also facilitates the initiation of extracranial optic-guided radiotherapy.

Initial clinical experience with frameless stereotactic radiosurgery: Analysis of accuracy and feasibility

PURPOSE To report on preliminary clinical experience with a novel image-guided frameless stereotactic radiosurgery system. METHODS AND MATERIALS Fifteen patients ranging in age from 14 to 81 received radiosurgery using a commercially available frameless stereotactic radiosurgery system. Pathologic diagnoses included metastases (12), recurrent primary intracranial sarcoma (1), recurrent central nervous system (CNS) lymphoma (1), and medulloblastoma with supratentorial seeding (1). Treatment accuracy was assessed from image localization of the stereotactic reference array and reproducibility of biteplate reseating. We chose 0.3 mm vector translation error and 0.3 degree rotation about each axis as the maximum tolerated misalignment before treating each arc. RESULTS The biteplates were found on average to reseat with a reproducibility of 0.24 mm. The mean registration error from CT localization was found to be 0.5 mm, which predicts that the average error at isocenter was 0.82 mm. No patient treatment was delivered beyond the maximum tolerated misalignment. The radiosurgery treatment was delivered in approximately 25 min per patient. CONCLUSION Our initial clinical experience with stereotactic radiotherapy using the infrared camera guidance system was promising, demonstrating clinical feasibility and accuracy comparable to many frame-based systems.

Linac radiosurgery for benign meningiomas

PURPOSE To review outcomes for patients treated with linac radiosurgery for benign meningiomas. METHODS AND MATERIALS Between January 1989 and July 1997, 70 patients with 76 meningiomas were treated with LINAC-based radiosurgery. In 38 patients, radiosurgery was the initial treatment. In 32 patients, radiosurgery followed surgery or conventional radiotherapy. The average treatment volume was 10.0 cm3 (range, 0.6 to 28.6 cm3). The mean peripheral dose was 12.7 Gy (range, 10 to 20 Gy). The mean clinical follow-up period was 23 months. No patient was lost to follow-up. RESULTS No lesions enlarged during the follow-up period; of 48 lesions in patients who had follow-up for at least one year and hence had follow-up imaging, 27 tumors remained unchanged and 21 tumors were reduced in size. Two patients experienced transient radiation-induced neurological deficits. One was treated with surgical excision of the tumor; the other responded to prolonged steroid therapy. Both patients, treated early in our experience, received doses higher than we would currently recommend. CONCLUSIONS Early results suggest that stereotactic radiosurgery is an effective treatment for meningiomas. Long-term follow-up will be necessary to fully evaluate its efficacy.

A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR).

DBS depends on precise placement of the stimulating electrode into an appropriate target region. Image-based (direct) targeting has been limited by the ability of current technology to visualize DBS targets. We have recently developed and employed a Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) 3T MRI sequence to more reliably visualize these structures. The FGATIR provides significantly better high resolution thin (1 mm) slice visualization of DBS targets than does either standard 3T T1 or T2-weighted imaging. The T1 subcortical image revealed relatively poor contrast among the targets for DBS, though the sequence did allow localization of striatum and thalamus. T2 FLAIR scans demonstrated better contrast between the STN, SNr, red nucleus (RN), and pallidum (GPe/GPi). The FGATIR scans allowed for localization of the thalamus, striatum, GPe/GPi, RN, and SNr and displayed sharper delineation of these structures. The FGATIR also revealed features not visible on other scan types: the internal lamina of the GPi, fiber bundles from the internal capsule piercing the striatum, and the boundaries of the STN. We hope that use of the FGATIR to aid initial targeting will translate in future studies to faster and more accurate procedures with consequent improvements in clinical outcomes.