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Mohamed Samy Elhammady and Roberto C. Heros

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David J. Salvetti, Tara G. Nagaraja, Carl Levy, Zhiyaun Xu and Jason Sheehan

Object

Increasingly, meningiomas are detected incidentally, prior to symptom development. While these lesions are traditionally managed conservatively until symptoms develop or lesion growth occurs, it is conceivable that patients at high risk for symptom development may benefit from earlier intervention prior to the appearance of symptoms. However, little research has been performed to determine whether Gamma Knife surgery (GKS) can alter the rate of symptom development in such patients.

Methods

A retrospective case study was performed by screening the University of Virginia GKS database for patients treated for asymptomatic meningiomas. From the patient's medical records, pertinent demographic and treatment information was obtained. Yearly follow-up MRI had been performed to assess tumor control and detect signs of radiation-induced injury. Clinical follow-up via neurological examination had been performed to assess symptom development.

Results

Forty-two patients, 33 females (78.6%) and 9 males (21.4%), with 42 asymptomatic meningiomas were included in the analysis. The median age at GKS was 53 years. The most common lesion location was the cerebral convexities (10 lesions [23.8%]), and the median lesion size was 4.0 ml. The median duration of imaging and clinical follow-ups was 59 and 76 months, respectively. During the follow-up period, 1 tumor (2.4%) increased in size, 2 patients (4.8%) demonstrated symptoms, and 1 patient (2.4%) exhibited possible signs of radiation-induced injury. Thus, actuarial tumor control rates were 100%, 95.7%, and 95.7% for 2, 5, and 10 years, respectively. Actuarial symptom control at 5 and 10 years was 97% and 93.1%, respectively. Overall progression-free survival was 91.1% and 77.8% at 5 and 10 years, respectively.

Conclusions

Compared with published rates of symptom development in patients with untreated meningiomas, results in this study indicated that patients with asymptomatic lesions may benefit from prophylactic radiosurgery prior to the appearance of symptoms. Additionally, GKS is a treatment option that offers low morbidity.

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Douglas Kondziolka

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David J. Salvetti, Tara G. Nagaraja, Ian T. McNeill, Zhiyuan Xu and Jason Sheehan

Object

It has been generally accepted that Gamma Knife surgery (GKS) is an effective primary or adjunct treatment for patients with 1–4 metastases to the brain. The number of studies detailing the use of GKS for 5 or more brain metastases, however, remains minimal. The aim of the current retrospective study was to elucidate the utility of GKS in patients with 5–15 brain metastases.

Methods

Patients were chosen for GKS based on prior MRI of these metastatic lesions and a known primary cancer diagnosis. Magnetic resonance imaging was used post-GKS to assess tumor control; patients were also followed up clinically. Overall survival (OS) from the date of GKS was used as the primary end point. Statistical analysis was performed to identify prognostic factors related to OS.

Results

Between 2003 and 2012, 96 patients were treated for a total of 704 metastatic brain lesions. The histology of these lesions varied among non–small cell lung cancer (NSCLC), breast cancer, melanoma, renal cancer, and other more rare carcinomas. At the initial treatment, 18 of the patients (18.8%) were categorized in Recursive Partitioning Analysis (RPA) Class 1 and 77 (80.2%) in RPA Class 2; none were in RPA Class 3. The median number of treated lesions was 7 (mean 7.13), and the median planned treatment volume was 6.12 cm3 (range 0.42–57.83 cm3) per patient. The median clinical follow-up was 4.1 months (range 0.1–40.70 months). Actuarial tumor control was calculated to be 92.4% at 6 months, 84.8% at 12 months, and 74.9% at 24 months post-GKS. The median OS was found to be 4.73 months (range 0.4–41.8 months). Multivariate analysis demonstrated that RPA class was a significant predictor of death (HR = 2.263, p = 0.038). Number of lesions, tumor histology, Graded Prognostic Assessment score, prior whole-brain radiation therapy, prior resection, prior chemotherapy, patient age, patient sex, controlled primary tumor, extracranial metastases, and planned treatment volume were not significant predictors of OS.

Conclusions

In patients with 5–15 brain metastases at presentation, the number of lesions did not predict survival after GKS; however, the RPA class was predictive of OS in this group of patients. Gamma Knife surgery for such patients offers an excellent rate of local tumor control.

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Yu-Hua Huang, Tao-Chen Lee, Tsung-Han Lee, Chen-Chieh Liao, Jason Sheehan and Aij-Lie Kwan

Object

Decompressive craniectomy is a life-saving measure for patients who have sustained traumatic brain injury (TBI), but patients undergoing this procedure may still die during an early phase of head injury. The aim of this study was to investigate the incidence, causes, and risk factors of 30-day mortality in traumatically brain-injured patients undergoing decompressive craniectomy.

Methods

The authors included 201 head-injured patients undergoing decompressive craniectomy in this 3-year retrospective study. The main outcome evaluated was 30-day mortality in patients who had undergone craniectomy after TBI. Demographic and clinical data, including information on death, were obtained for subsequent analysis. The authors identified differences between survivors and nonsurvivors in terms of clinical parameters; multivariate logistic regression was used to adjust for independent risk factors of short-term death.

Results

The 30-day mortality rate was 26.4% in traumatically brain-injured patients undergoing decompressive craniectomy. The majority of deaths following decompression resulted from uncontrollable brain swelling and extensive brain infarction, which accounted for 79.2% of mortality. In the multivariate logistic regression mode, the 2 independent risk factors for 30-day mortality were age (OR 1.035 [95% CI 1.006–1.064]; p = 0.018) and Glasgow Coma Scale (GCS) score before decompressive craniectomy (OR 0.769 [95% CI 0.597–0.990]; p = 0.041).

Conclusions

There is a high 30-day mortality rate in traumatically brain-injured patients undergoing decompressive craniectomy. Most of the deaths are attributed to ongoing brain damage, even after decompression. Risk factors of short-term death, including age and preoperative GCS score, are important in patient selection for decompressive craniectomy, and these factors should be considered together to ensure the highest chance of surviving TBI.

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Stephen J. Monteith, Sagi Harnof, Ricky Medel, Britney Popp, Max Wintermark, M. Beatriz S. Lopes, Neal F. Kassell, W. Jeff Elias, John Snell, Matthew Eames, Eyal Zadicario, Krisztina Moldovan and Jason Sheehan

Object

Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube.

Methods and Results

In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance.

Conclusions

The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

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Fu-Chou Cheng, Meei-Ling Sheu, Hong-Lin Su, Ying-Ju Chen, Chun-Jung Chen, Wen-Ta Chiu, Jason Sheehan and Hung-Chuan Pan

Object

Mobilization of hematopoietic progenitor cells (HPCs) from bone marrow involved in the process of peripheral nerve regeneration occurs mostly through deposits of CD34+ cells. Treadmill exercise, with either differing intensity or duration, has been shown to increase axon regeneration and sprouting, but the effect of mobilization of HPCs on peripheral nerve regeneration due to treadmill exercise has not yet been elucidated.

Methods

Peripheral nerve injury was induced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were categorized into 2 groups: those with and without treadmill exercise (20 m/min for 60 minutes per day for 7 days). Cytospin and flow cytometry were used to determine bone marrow progenitor cell density and distribution. Neurobehavioral analysis, electrophysiological study, and regeneration marker expression were investigated at 1 and 3 weeks after exercise. The accumulation of HPCs, immune cells, and angiogenesis factors in injured nerves was determined. A separate chimeric mice study was conducted to assess CD34+ cell distribution according to treadmill exercise group.

Results

Treadmill exercise significantly promoted nerve regeneration. Increased Schwann cell proliferation, increased neurofilament expression, and decreased Schwann cell apoptosis were observed 7 days after treadmill exercise. Elevated expression of S100 and Luxol fast blue, as well as decreased numbers of vacuoles, were identified in the crushed nerve 3 weeks after treadmill exercise. Significantly increased numbers of mononuclear cells, particularly CD34+ cells, were induced in bone marrow after treadmill exercise. The deposition of CD34+ cells was abolished by bone marrow irradiation. In addition, deposits of CD34+ cells in crushed nerves paralleled the elevated expressions of von Willebrand factor, isolectin B4, and vascular endothelial growth factor.

Conclusions

Bone marrow HPCs, especially CD34+ cells, were able to be mobilized by low-intensity treadmill exercise, and this effect paralleled the significant expression of angiogenesis factors. Treadmill exercise stimulation of HPC mobilization during peripheral nerve regeneration could be used as a therapy in human beings.

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Stephen Monteith, Jason Sheehan, Ricky Medel, Max Wintermark, Matthew Eames, John Snell, Neal F. Kassell and W. Jeff Elias

Magnetic resonance–guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

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L. Dade Lunsford, Veronica Chiang, John R. Adler, Jason Sheehan, William Friedman and Douglas Kondziolka