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Fred Rincon, Errol Gordon, Robert M. Starke, Manuel M. Buitrago, Andres Fernandez, J. Michael Schmidt, Jan Claassen, Katja E. Wartenberg, Jennifer Frontera, David B. Seder, David Palestrant, E. Sander Connolly, Kiwon Lee, Stephan A. Mayer and Neeraj Badjatia

Object

The purpose of this study was to identify predictors of shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH).

Methods

The authors evaluated the incidence of shunt-dependent hydrocephalus in a consecutive cohort of 580 patients with SAH who were admitted to the Neurological Intensive Care Unit of Columbia University Medical Center between July 1996 and September 2002. Patient demographics, 24-hour admission variables, initial CT scan characteristics, daily transcranial Doppler variables, and development of in-hospital complications were analyzed. Odds ratios and 95% CIs for candidate predictors were calculated using multivariate nominal logistic regression.

Results

Admission glucose of at least 126 mg/dl (adjusted OR 1.6; 95% CI 1.0–2.6), admission brain CT scan with a bicaudate index of at least 0.20 (adjusted OR 1.43; 95% CI 1.0–2.0), Fisher Grade 4 (adjusted OR 2.71; 95% CI 1.2–5.7), fourth ventricle hemorrhage (adjusted OR 1.78; 95% CI 1.1–2.7), and development of nosocomial meningitis (adjusted OR 2.2; 95% CI 1.4–3.7) were independently associated with shunt dependency.

Conclusions

These data suggest that permanent CSF diversion after aneurysmal SAH may be independently predicted by hyperglycemia at admission, findings on the admission CT scan (Fisher Grade 4, fourth ventricle intraventricular hemorrhage, and bicaudate index ≥ 0.20), and development of nosocomial meningitis. Future research is needed to assess if tight glycemic control, reduction of fourth ventricle clot burden, and prevention of nosocomial meningitis may reduce the need for permanent CSF diversion after aneurysmal SAH.

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John H. Sampson, Shivanand P. Lad, James E. Herndon II, Robert M. Starke and Douglas Kondziolka

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Or Cohen-Inbar, Robert M. Starke, Hideyuki Kano, Gregory Bowden, Paul Huang, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, David Mathieu, Danilo Silva, Mahmoud Abbassy, Symeon Missios, John Y. K. Lee, Gene H. Barnett, Douglas Kondziolka, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Cerebellar arteriovenous malformations (AVMs) represent the majority of infratentorial AVMs and frequently have a hemorrhagic presentation. In this multicenter study, the authors review outcomes of cerebellar AVMs after stereotactic radiosurgery (SRS).

METHODS

Eight medical centers contributed data from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65% presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent radiation-induced complications (RICs). Patients were followed clinically and radiographically, with a median follow-up of 60 months (range 7–325 months).

RESULTS

The overall actuarial rates of obliteration at 3, 5, 7, and 10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session SRS. Obliteration and a favorable outcome were more likely to be achieved in patients treated with a margin dose greater than 18 Gy (p < 0.001 for both), demonstrating significantly better rates (83.3% and 79%, respectively). The rate of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable outcome.

CONCLUSIONS

SRS results in successful obliteration and a favorable outcome in the majority of patients with cerebellar AVMs. Most patients will require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical and not microsurgical scales were predictive of clinical outcome after SRS.

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Or Cohen-Inbar, Robert M. Starke, Gabriella Paisan, Hideyuki Kano, Paul P. Huang, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, David Mathieu, Danilo Silva, Mahmoud Abbassy, Symeon Missios, John Y. K. Lee, Gene H. Barnett, Douglas Kondziolka, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

The goal of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) is complete nidus obliteration, thereby eliminating the risk of future hemorrhage. This outcome can be observed within the first 18 months, although documentation of AVM obliteration can extend to as much as 5 years after SRS is performed. A shorter time to obliteration may impact the frequency and effect of post-SRS complications and latency hemorrhage. The authors' goal in the present study was to determine predictors of early obliteration (18 months or less) following SRS for cerebral AVM.

METHODS

Eight centers participating in the International Gamma Knife Research Foundation (IGKRF) obtained institutional review board approval to supply de-identified patient data. From a cohort of 2231 patients, a total of 1398 patients had confirmed AVM obliteration. Patients were sorted into early responders (198 patients), defined as those with confirmed nidus obliteration at or prior to 18 months after SRS, and late responders (1200 patients), defined as those with confirmed nidus obliteration more than 18 months after SRS. The median clinical follow-up time was 63.7 months (range 7–324.7 months).

RESULTS

Outcome parameters including latency interval hemorrhage, mortality, and favorable outcome were not significantly different between the 2 groups. Radiologically demonstrated radiation-induced changes were noted more often in the late responder group (376 patients [31.3%] vs 39 patients [19.7%] for early responders, p = 0.005). Multivariate independent predictors of early obliteration included a margin dose > 24 Gy (p = 0.031), prior surgery (p = 0.002), no prior radiotherapy (p = 0.025), smaller AVM nidus (p = 0.002), deep venous drainage (p = 0.039), and nidus location (p < 0.0001). Basal ganglia, cerebellum, and frontal lobe nidus locations favored early obliteration (p = 0.009). The Virginia Radiosurgery AVM Scale (VRAS) score was significantly different between the 2 responder groups (p = 0.039). The VRAS score was also shown to be predictive of early obliteration on univariate analysis (p = 0.009). For early obliteration, such prognostic ability was not shown for other SRS- and AVM-related grading systems.

CONCLUSIONS

Early obliteration (≤ 18 months post-SRS) was more common in patients whose AVMs were smaller, located in the frontal lobe, basal ganglia, or cerebellum, had deep venous drainage, and had received a margin dose > 24 Gy.

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David Hasan, Mario Zanaty, Robert M. Starke, Elias Atallah, Nohra Chalouhi, Pascal Jabbour, Amit Singla, Waldo R. Guerrero, Daichi Nakagawa, Edgar A. Samaniego, Nnenna Mbabuike, Rabih G. Tawk, Adnan H. Siddiqui, Elad I. Levy, Roberta L. Novakovic, Jonathan White, Clemens M. Schirmer, Thomas G. Brott, Hussain Shallwani and L. Nelson Hopkins

OBJECTIVE

The overall risk of ischemic stroke from a chronically occluded internal carotid artery (COICA) is around 5%–7% per year despite receiving the best available medical therapy. Here, authors propose a radiographic classification of COICA that can be used as a guide to determine the technical success and safety of endovascular recanalization for symptomatic COICA and to assess the changes in systemic blood pressure following successful revascularization.

METHODS

The radiographic images of 100 consecutive subjects with COICA were analyzed. A new classification of COICA was proposed based on the morphology, location of occlusion, and presence or absence of reconstitution of the distal ICA. The classification was used to predict successful revascularization in 32 symptomatic COICAs in 31 patients, five of whom were female (5/31 [16.13%]). Patients were included in the study if they had a COICA with ischemic symptoms refractory to medical therapy. Carotid artery occlusion was defined as 100% cross-sectional occlusion of the vessel lumen as documented on CTA or MRA and confirmed by digital subtraction angiography.

RESULTS

Four types (A–D) of radiographic COICA were identified. Types A and B were more amenable to safe revascularization than types C and D. Recanalization was successful at a rate of 68.75% (22/32 COICAs; type A: 8/8; type B: 8/8; type C: 4/8; type D: 2/8). The perioperative complication rate was 18.75% (6/32; type A: 0/8 [0%]; type B: 1/8 [12.50%]; type C: 3/8 [37.50%], type D: 2/8 [25.00%]). None of these complications led to permanent morbidity or death. Twenty (64.52%) of 31 subjects had improvement in their symptoms at the 2–6 months’ follow-up. A statistically significant decrease in systolic blood pressure (SBP) was noted in 17/21 (80.95%) patients who had successful revascularization, which persisted on follow-up (p = 0.0001). The remaining 10 subjects in whom revascularization failed had no significant changes in SBP (p = 0.73).

CONCLUSIONS

The pilot study suggested that our proposed classification of COICA may be useful as an adjunctive guide to determine the technical feasibility and safety of revascularization for symptomatic COICA using endovascular techniques. Additionally, successful revascularization may lead to a significant decrease in SBP postprocedure. A Phase 2b trial in larger cohorts to assess the efficacy of endovascular revascularization using our COICA classification is warranted.

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Mohana Rao Patibandla, Dale Ding, Hideyuki Kano, Robert M. Starke, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, Paul P. Huang, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

The role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.

METHODS

The authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988–2000) or modern (2001–2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).

RESULTS

The study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.

CONCLUSIONS

Despite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.

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Dale Ding, Robert M. Starke, Hideyuki Kano, John Y. K. Lee, David Mathieu, John Pierce, Paul P. Huang, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Douglas Kondziolka, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes.

METHODS

The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses.

RESULTS

The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm3, 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis.

CONCLUSIONS

Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.

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Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan McShane, John Lee, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Mohana Rao Patibandla, Christopher P. Cifarelli, Gabriella Paisan, John A. Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

In this multicenter study, the authors reviewed the results obtained in patients who underwent Gamma Knife radiosurgery (GKRS) for dural arteriovenous fistulas (dAVFs) and determined predictors of outcome.

METHODS

Data from a cohort of 114 patients who underwent GKRS for cerebral dAVFs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as dAVF obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and dAVF characteristics were assessed to determine predictors of outcome in a multivariate logistic regression analysis; dAVF-free obliteration was calculated in a competing-risk survival analysis; and Youden indices were used to determine optimal radiosurgical dose.

RESULTS

A mean margin dose of 21.8 Gy was delivered. The mean follow-up duration was 4 years (range 0.5–18 years). The overall obliteration rate was 68.4%. The postradiosurgery actuarial rates of obliteration at 3, 5, 7, and 10 years were 41.3%, 61.1%, 70.1%, and 82.0%, respectively. Post-GRKS hemorrhage occurred in 4 patients (annual risk of 0.9%). Radiation-induced imaging changes occurred in 10.4% of patients; 5.2% were symptomatic, and 3.5% had permanent deficits. Favorable outcome was achieved in 63.2% of patients. Patients with middle fossa and tentorial dAVFs (OR 2.4, p = 0.048) and those receiving a margin dose greater than 23 Gy (OR 2.6, p = 0.030) were less likely to achieve a favorable outcome. Commonly used grading scales (e.g., Borden and Cognard) were not predictive of outcome. Female sex (OR 1.7, p = 0.03), absent venous ectasia (OR 3.4, p < 0.001), and cavernous carotid location (OR 2.1, p = 0.019) were predictors of GKRS-induced dAVF obliteration.

CONCLUSIONS

GKRS for cerebral dAVFs achieved obliteration and avoided permanent complications in the majority of patients. Those with cavernous carotid location and no venous ectasia were more likely to have fistula obliteration following radiosurgery. Commonly used grading scales were not reliable predictors of outcome following radiosurgery.

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Robert M. Starke, Hideyuki Kano, Dale Ding, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, Paul P. Huang, Douglas Kondziolka, Chun-Po Yen, Caleb Feliciano, Rafael Rodgriguez-Mercado, Luis Almodovar, Daniel R. Pieper, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

In this multicenter study, the authors reviewed the results following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs), determined predictors of outcome, and assessed predictive value of commonly used grading scales based upon this large cohort with long-term follow-up.

METHODS

Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed.

RESULTS

The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1–20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment.

CONCLUSIONS

GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery.

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Jason P. Sheehan, Robert M. Starke, Hideyuki Kano, Anthony M. Kaufmann, David Mathieu, Fred A. Zeiler, Michael West, Samuel T. Chao, Gandhi Varma, Veronica L. S. Chiang, James B. Yu, Heyoung L. McBride, Peter Nakaji, Emad Youssef, Norissa Honea, Stephen Rush, Douglas Kondziolka, John Y. K. Lee, Robert L. Bailey, Sandeep Kunwar, Paula Petti and L. Dade Lunsford

Object

Parasellar and sellar meningiomas are challenging tumors owing in part to their proximity to important neurovascular and endocrine structures. Complete resection can be associated with significant morbidity, and incomplete resections are common. In this study, the authors evaluated the outcomes of parasellar and sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an adjunct to microsurgical removal or conventional radiation therapy and as a primary treatment modality.

Methods

A multicenter study of patients with benign sellar and parasellar meningiomas was conducted through the North American Gamma Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors identified all patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were also required to have a minimum of 6 months of imaging and clinical follow-up after GKRS. Factors predictive of new neurological deficits following GKRS were assessed via univariate and multivariate analyses. Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.

Results

The authors identified 763 patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were assessed clinically and with neuroimaging at routine intervals following GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of 56 years (range 8–90 years). Three hundred fifty-five patients (50.7%) had undergone at least one resection before GKRS, and 3.8% had undergone prior radiation therapy. The median follow-up after GKRS was 66.7 months (range 6–216 months). At the last follow-up, tumor volumes remained stable or decreased in 90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10 years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery, prior radiation therapy, or a tumor margin dose < 13 Gy significantly increased the likelihood of tumor progression after GKRS.

At the last clinical follow-up, 86.2% of patients demonstrated no change or improvement in their neurological condition, whereas 13.8% of patients experienced symptom progression. New or worsening cranial nerve deficits were seen in 9.6% of patients, with cranial nerve (CN) V being the most adversely affected nerve. Functional improvements in CNs, especially in CNs V and VI, were observed in 34% of patients with preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6% of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome with tumor growth and accompanying neurological decline was statistically more likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior surgery (p = 0.021).

Conclusions

Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients.