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Mark Quigg, Chun-Po Yen, Micaela Chatman, Anders H. Quigg, Ian T. McNeill, Colin J. Przybylowski, Guofen Yan, and Jason P. Sheehan

Object

Diabetes mellitus (DM) and hypertension may be associated with complications following fractionated radiotherapy. To date no studies have determined the risk of radiation toxicity in patients with DM or hypertension who have undergone Gamma Knife surgery (GKS) for brain arteriovenous malformations (AVMs). The goal of the present study was to determine associations between DM or hypertension and other factors in the development of radiotoxicity, as measured by radiation-induced changes (RICs) on MR images following radiosurgery for AVM.

Methods

Using univariate methods and multivariate logistic regression, the authors compared the RIC status in patients 18 years of age and older with these patients' history of, or medication use for, DM or hypertension; tobacco use; patient age and sex; AVM volume; Spetzler-Martin AVM severity scale (Grades I and II vs Grades III–V); AVM surgery, AVM embolization, or hemorrhage prior to radiosurgery; AVM location; number of draining veins; and radiosurgery margin dose.

Results

Radiation-induced changes occurred in 38% of 539 adults within a mean (± standard deviation) of 12 ± 10 months after radiosurgery, as observed during a median follow-up time of 55 months. Among patients in whom RICs occurred, 34% had headaches, neurological deficits, or new-onset seizures. Larger RICs were associated with worse symptoms. According to a univariate analysis, DM (3% of patients), larger AVM volume, worse Spetzler-Martin grade, lack of AVM surgery prior to radiosurgery, lack of hemorrhage prior to radiosurgery, and smaller margin dose of radiation had significant associations with the presence of RICs. Hypertension (20%), patient sex, tobacco use, number of draining veins, superficial or deep location of the lesion, and AVM embolization prior to radiosurgery had no association with the presence of RICs. According to a multivariate analysis, larger AVM volume, worse Spetzler-Martin grade, and no AVM surgery prior to radiosurgery predicted the occurrence of an RIC. Diabetes mellitus had borderline significance.

Conclusions

Vascular factors such as hypertension, patient sex, and tobacco use did not convey additional risks of radiotoxicity, but DM remained a possible cardiovascular risk factor in the development of RICs.

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Ching-Hsiao Cheng, R. Webster Crowley, Chun-Po Yen, David Schlesinger, Mark E. Shaffrey, and Jason P. Sheehan

Object

Gamma Knife surgery (GKS) has emerged as the treatment of choice for small- to medium-sized cerebral arteriovenous malformations (AVMs) in deep locations. The present study aims to investigate the outcomes of GKS for AVMs in the basal ganglia and thalamus.

Methods

Between 1989 and 2007, 85 patients with AVMs in the basal ganglia and 97 in the thalamus underwent GKS and were followed up for more than 2 years. The nidus volumes ranged from 0.1 to 29.4 cm3 (mean 3.4 cm3). The mean margin dose at the initial GKS was 21.3 Gy (range 10–28 Gy). Thirty-six patients underwent repeat GKS for residual AVMs at a median 4 years after initial GKS. The mean margin dose at repeat GKS was 21.1 Gy (range 7.5–27 Gy).

Results

Following a single GKS, total obliteration of the nidus was confirmed on angiograms in 91 patients (50%). In 12 patients (6.6%) a subtotal obliteration was achieved. No flow voids were observed on MR imaging in 14 patients (7.7%). Following single or repeat GKS, total obliteration was angiographically confirmed in 106 patients (58.2%) and subtotal obliteration in 8 patients (4.4%). No flow voids on MR imaging were observed in 18 patients (9.9%). The overall obliteration rates following one or multiple GKSs based on MR imaging or angiography was 68%. A small nidus volume, high margin dose, low number of isocenters, and no history of embolization were significantly associated with an increased rate of obliteration. Twenty-one patients experienced 25 episodes of hemorrhage in 850 risk-years following GKS, yielding an annual hemorrhage rate of 2.9%. Four patients died in this series: 2 due to complications of hemorrhage and 2 due to unrelated diseases. Permanent neurological deficits caused by radiation were noted in 9 patients (4.9%).

Conclusions

Gamma Knife surgery offers a reasonable chance of obliterating basal ganglia and thalamic AVMs and does so with a low risk of complications. It is an optimal treatment option in patients for whom the anticipated risk of microsurgery is too high.

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Ayhan Kanat

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Chun Po Yen, Stephen J. Monteith, James H. Nguyen, Jessica Rainey, David J. Schlesinger, and Jason P. Sheehan

Object

The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS).

Methods

Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm3 at the time of GKS, and a mean prescription dose of 21.9 Gy was used.

Results

After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career.

Conclusions

Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

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Dibyendu Kumar Ray, Chun Po Yen, Mary Lee Vance, Edward R. Laws, Beatriz Lopes, and Jason P. Sheehan

Lymphocytic hypophysitis is a relatively uncommon autoimmune inflammatory disorder affecting the pituitary gland. It most frequently occurs in women of child-bearing age. The authors report on their experience with a patient who presented with diplopia and marked enlargement of the pituitary gland. She underwent transsphenoidal surgery, and histopathological analysis confirmed the diagnosis of lymphocytic hypophysitis. The disease proved refractory to resection, and any attempt at withdrawal of corticosteroid therapy resulted in a return of the patient's symptoms and enlargement of the sellar contents.

The patient underwent Gamma Knife surgery (GKS) to the sella and both cavernous sinuses. After GKS, the patient was able to discontinue steroid therapy without return of her symptoms. Follow-up MR images demonstrated no evidence of recurrence of lymphocytic hypophysitis.

For persistent lymphocytic hypophysitis, GKS is a reasonable treatment option.

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Chun Po Yen, Jason Sheehan, Melita Steiner, Greg Patterson, and Ladislau Steiner

Object

Focal tumors, a distinct subgroup of which is composed of brainstem gliomas, may have an indolent clinical course. In the past, their management involved monitoring of open-ended imaging studies and shunt placement if cerebrospinal fluid diversion was required. Nonetheless, their treatment remains a significant challenge for neurosurgeons. Gamma Knife surgery (GKS) has recently been tried as an alternative to surgical extirpation. In the present study the authors assess clinical and imaging results in 20 patients who harbored focal brainstem gliomas treated with GKS between 1990 and 2001.

Methods

There were 10 male and 10 female patients with a mean age of 19.1 years. Sixteen tumors were located in the midbrain, three in the pons, and one in the medulla oblongata. The mean tumor volume at the time of GKS was 2.5 cm3. In 10 cases a tumor specimen was obtained either by open surgery or stereotactic biopsy, securing the diagnosis of pilocytic astrocytoma in five patients and nonpilocytic astrocytoma in five others. In the remaining 10 cases, the diagnosis was based on clinical and neuroimaging findings. The prescription Gamma Knife dose varied between 10 and 18 Gy, except in three patients who were receiving a boost to a site in which external-beam radiation was previously delivered. An average of four isocenters were utilized per GKS.

Patients were followed up for a mean of 78.0 months. The tumors disappeared in four patients and shrank in 12 patients. Of these patients, one experienced transitory extrapyramidal symptoms and fluctuating impairment of consciousness (from somnolence to coma) for 6 months. Another patient whose tumor disappeared 3 years following GKS died of stroke 8 years postoperatively. The rest of the patients either remained stable or improved clinically. Tumor progression occurred in four patients; of these four, one patient developed hydrocephalus requiring a ventriculoperitoneal shunt, two showed neurological deterioration, and one 4-year-old boy died of tumor progression.

Conclusions

Gamma Knife surgery may be an effective primary treatment or adjunct to open surgery for focal brainstem gliomas.

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Chun-Po Yen, Julie A. Matsumoto, Max Wintermark, Lucia Schwyzer, Avery J. Evans, Mary E. Jensen, Mark E. Shaffrey, and Jason P. Sheehan

Object

The objective of this study was to evaluate the incidence, severity, clinical manifestations, and risk factors of radiation-induced imaging changes (RIICs) following Gamma Knife surgery (GKS) for cerebral arteriovenous malformations (AVMs).

Methods

A total of 1426 GKS procedures performed for AVMs with imaging follow-up available were analyzed. Radiation-induced imaging changes were defined as newly developed increased T2 signal surrounding the treated AVM nidi. A grading system was developed to categorize the severity of RIICs. Grade I RIICs were mild imaging changes imposing no mass effect on the surrounding brain. Grade II RIICs were moderate changes causing effacement of the sulci or compression of the ventricles. Grade III RIICs were severe changes causing midline shift of the brain. Univariate and multivariate logistic regression analyses were applied to test factors potentially affecting the occurrence, severity, and associated symptoms of RIICs.

Results

A total of 482 nidi (33.8%) developed RIICs following GKS, with 281 classified as Grade I, 164 as Grade II, and 37 as Grade III. The median duration from GKS to the development of RIICs was 13 months (range 2–124 months). The imaging changes disappeared completely within 2–128 months (median 22 months) following the development of RIICs. The RIICs were symptomatic in 122 patients, yielding an overall incidence of symptomatic RIICs of 8.6%. Twenty-six patients (1.8%) with RIICs had permanent deficits. A negative history of prior surgery, no prior hemorrhage, large nidus, and a single draining vein were associated with a higher risk of RIICs.

Conclusions

Radiation-induced imaging changes are the most common adverse effects following GKS. Fortunately, few of the RIICs are symptomatic and most of the symptoms are reversible. Patients with a relatively healthy brain and nidi that are large, or with a single draining vein, are more likely to develop RIICs.

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Robert G. Louis Jr., Chun Po Yen, Carrie A. Mohila, James W. Mandell, and Jason Sheehan

The authors report the case of a patient with an intraosseous spinal arteriovenous malformation (AVM) presenting as an epidural mass lesion that was causing spinal cord compression. The 59-year-old woman had bilateral numbness, weakness, and hyperreflexia of both legs. Magnetic resonance imaging revealed intermediate T1 signal and hyperintense T2 signal involving the right transverse process, bilateral pedicles, and T-5 spinous process; the lesion's epidural extension was causing severe canal compromise and cord displacement. Coil embolization was performed, and the patient underwent resection, after which preoperative symptoms improved. Histopathological analysis revealed a benign vascular proliferation consistent with an intraosseous spinal AVM. On review of the literature, the authors found this case to be the second intraosseous spinal AVM, and the first in a patient whose clinical presentation was consistent with that of a mass lesion of the bone.

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E. Sander Connolly Jr.