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Nohra Chalouhi, Nikolaos Mouchtouris, Fadi Al Saiegh, Somnath Das, Ahmad Sweid, Adam E. Flanders, Robert M. Starke, Michael P. Baldassari, Stavropoula Tjoumakaris, Michael Reid Gooch, Syed Omar Shah, David Hasan, Nabeel Herial, Robin D’Ambrosio, Robert Rosenwasser and Pascal Jabbour

OBJECTIVE

MRI and MRA studies are routinely obtained to identify the etiology of intracerebral hemorrhage (ICH). The diagnostic yield of MRI/MRA in the setting of an acute ICH, however, remains unclear. The authors’ goal was to determine the utility of early MRI/MRA in detecting underlying structural lesions in ICH and to identify patients in whom additional imaging during hospitalization could safely be foregone.

METHODS

The authors reviewed data obtained in 400 patients with spontaneous ICH diagnosed on noncontrast head CT scans who underwent MRI/MRA between 2015 and 2017 at their institution. MRI/MRA studies were reviewed to identify underlying lesions, such as arteriovenous malformations, aneurysms, cavernous malformations, arteriovenous fistulas, tumors, sinus thrombosis, moyamoya disease, and abscesses.

RESULTS

The median patient age was 65 ± 15.8 years. Hypertension was the most common (72%) comorbidity. Structural abnormalities were detected on MRI/MRA in 12.5% of patients. Structural lesions were seen in 5.7% of patients with basal ganglia/thalamic ICH, 14.1% of those with lobar ICH, 20.4% of those with cerebellar ICH, and 27.8% of those with brainstem ICH. Notably, the diagnostic yield of MRI/MRA was 0% in patients > 65 years with a basal ganglia/thalamic hemorrhage and 0% in those > 85 years with any ICH location, whereas it was 37% in patients < 50 years and 23% in those < 65 years. Multivariate analysis showed that decreasing age, absence of hypertension, and non–basal ganglia/thalamic location were predictors of finding an underlying lesion.

CONCLUSIONS

The yield of MRI/MRA in ICH is highly variable, depending on patient age and hemorrhage location. The findings of this study do not support obtaining early MRI/MRA studies in patients ≥ 65 years with basal ganglia/thalamic ICH or in any ICH patients ≥ 85 years. In all other situations, early MRI/MRA remains valuable in ruling out underlying lesions.

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Nohra Chalouhi, Alex Whiting, Eliza C. Anderson, Samantha Witte, Mario Zanaty, Stavropoula Tjoumakaris, L. Fernando Gonzalez, David Hasan, Robert M. Starke, Shannon Hann, George M. Ghobrial, Robert Rosenwasser and Pascal Jabbour

Object

It is common practice to use a new contralateral bur hole for ventriculoperitoneal shunt (VPS) placement in subarachnoid hemorrhage (SAH) patients with an existing ventriculostomy. At Thomas Jefferson University and Jefferson Hospital for Neuroscience, the authors have primarily used the ventriculostomy site for the VPS. The purpose of this study was to compare the safety of the 2 techniques in patients with SAH.

Methods

The rates of VPS-related hemorrhage, infection, and proximal revision were compared between the 2 techniques in 523 patients undergoing VPS placement (same site in 464 and contralateral site in 59 patients).

Results

The rate of new VPS-related hemorrhage was significantly higher in the contralateral-site group (1.7%) than in the same-site group (0%; p = 0.006). The rate of VPS infection did not differ between the 2 groups (6.4% for same site vs 5.1% for contralateral site; p = 0.7). In multivariate analysis, higher Hunt and Hess grades (p = 0.05) and open versus endovascular treatment (p = 0.04) predicted shunt infection, but the VPS technique was not a predictive factor (p = 0.9). The rate of proximal shunt revision was 6% in the same-site group versus 8.5% in the contralateralsite group (p = 0.4). In multivariate analysis, open surgery was the only factor predicting proximal VPS revision (p = 0.05).

Conclusions

The results of this study suggest that the use of the ventriculostomy site for VPS placement may be feasible and safe and may not add morbidity (infection or need for revision) compared with the use of a fresh contralateral site. This rapid and simple technique also was associated with a lower risk of shunt-related hemorrhage. While both techniques appear to be feasible and safe, a definitive answer to the question of which technique is superior awaits a higher level of medical evidence.

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Grace H. Kim, Christopher P. Kellner, David K. Hahn, Brianna M. Desantis, Muhith Musabbir, Robert M. Starke, Michal Rynkowski, Ricardo J. Komotar, Marc L. Otten, Robert Sciacca, J. Michael Schmidt, Stephan A. Mayer and E. Sander Connolly Jr.

Object

Despite efforts to elucidate both the molecular mechanism and the clinical predictors of vasospasm after aneurysmal subarachnoid hemorrhage (ASAH), its pathogenesis remains unclear. Monocyte chemoattractant protein–1 (MCP-1) is a chemokine that has been firmly implicated in the pathophysiology of vasospasm and in neural tissue injury following focal ischemia in both animal models and human studies. The authors hypothesized that MCP-1 would be found in increased concentrations in the blood and cerebrospinal fluid (CSF) of patients with ASAH and would correlate with both outcome and the occurrence of vasospasm.

Methods

Seventy-seven patients who presented with ASAH were prospectively enrolled in this study between July 2001 and May 2002. Using an enzyme-linked immunosorbent assay, MCP-1 levels were measured in serum daily and in CSF when available. The mean serum and CSF MCP-1 concentrations were calculated for each patient throughout the entire hospital stay. Neurological outcome was evaluated at discharge or 14 days posthemorrhage using the modified Rankin Scale. Vasospasm was evaluated on angiography.

Results

The serum MCP-1 concentrations correlated with negative outcome such that a 10% increase in concentration predicted a 25% increase in the probability of a poor outcome, whereas the serum MCP-1 levels did not correlate with vasospasm. Concentrations of MCP-1 in the CSF, however, proved to be significantly higher in patients with angiographically demonstrated vasospasm.

Conclusions

These findings suggest a role for MCP-1 in neurological injury and imply that it may act as a biomarker of poor outcome in the serum and of vasospasm in the CSF.

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Yasunori Nagahama, Lauren Allan, Daichi Nakagawa, Mario Zanaty, Robert M. Starke, Nohra Chalouhi, Pascal Jabbour, Robert D. Brown Jr., Colin P. Derdeyn, Enrique C. Leira, Joseph Broderick, Marc Chimowitz, James C. Torner and David Hasan

OBJECTIVE

Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories involving platelet activation have been postulated as potential explanations of the development of clinical vasospasm and DCI. However, the effects of dual antiplatelet therapy (DAPT; aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients.

METHODS

Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into 2 groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the 2 groups, utilizing univariate and multivariate logistic regression.

RESULTS

Of 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (OR 0.244, CI 95% 0.097–0.615, p = 0.003) and DCI (OR 0.056, CI 95% 0.01–0.318, p = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% vs 2%, p = 0.9).

CONCLUSIONS

The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.

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Mario Zanaty, Susanna Howard, Jorge A. Roa, Carlos M. Alvarez, David K. Kung, David J. McCarthy, Edgar A. Samaniego, Daichi Nakagawa, Robert M. Starke, Kaustubh Limaye, Sami Al Kasab, Nohra Chalouhi, Pascal Jabbour, James Torner, Daniel Tranel and David Hasan

OBJECTIVE

Revascularization of a symptomatic, medically refractory, cervical chronically occluded internal carotid artery (COICA) using endovascular techniques (ETs) has surfaced as a viable alternative to extracranial-intracranial bypass. The authors aimed to assess the safety, success, and neurocognitive outcomes of recanalization of COICA using ETs or hybrid treatment (ET plus carotid endarterectomy) and to identify candidate radiological markers that could predict success.

METHODS

The authors performed a retrospective analysis of their prospectively collected institutional database and used their previously published COICA classification to assess the potential benefits of ETs or hybrid surgery to revascularize symptomatic patients with COICA. Subjects who had undergone CT perfusion (CTP) imaging and Montreal Cognitive Assessment (MoCA) testing, both pre- and postprocedure, were included. The authors then performed a review of the literature on patients with COICA to further evaluate the success and safety of these treatment alternatives.

RESULTS

The single-center study revealed 28 subjects who had undergone revascularization of symptomatic COICA. Five subjects had CTP imaging and MoCA testing pre- and postrevascularization and thus were included in the study. All 5 patients had very large penumbra involving the entire hemisphere supplied by the ipsilateral COICA, which resolved postoperatively. Significant improvement in neurocognitive outcome was demonstrated by MoCA testing after treatment (preprocedure: 19.8 ± 2.4, postprocedure: 27 ± 1.6; p = 0.0038). Moreover, successful revascularization of COICA led to full restoration of cerebral hemodynamics in all cases. Review of the literature identified a total of 333 patients with COICA. Of these, 232 (70%) showed successful recanalization after ETs or hybrid surgery, with low major and minor complication rates (3.9% and 2.7%, respectively).

CONCLUSIONS

ETs and hybrid surgery are safe and effective alternatives to revascularize patients with symptomatic COICA. CTP imaging could be used as a radiological marker to assess cerebral hemodynamics and predict the success of revascularization. Improvement in CTP parameters is associated with significant improvement in neurocognitive functions.

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Jason P. Sheehan, Robert M. Starke, Hideyuki Kano, Gene H. Barnett, David Mathieu, Veronica Chiang, James B. Yu, Judith Hess, Heyoung L. McBride, Norissa Honea, Peter Nakaji, John Y. K. Lee, Gazanfar Rahmathulla, Wendi A. Evanoff, Michelle Alonso-Basanta and L. Dade Lunsford

OBJECT

Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa.

METHODS

At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12–89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm3, and a median margin dose of 13.6 Gy (range 8–40 Gy) was delivered to the tumor.

RESULTS

At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30–4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69–15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01–1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01–1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05–3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively.

CONCLUSIONS

Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation for patients with posterior fossa meningiomas. Those with a smaller tumor volume and no prior radiation therapy were more likely to have a favorable response after radiosurgery. Rarely, additional procedures may be required for hydrocephalus or tumor progression.

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Robert M. Starke, Ricardo J. Komotar, Zachary L. Hickman, Yehuda E. Paz, Angela G. Pugliese, Marc L. Otten, Matthew C. Garrett, Mitchell S. V. Elkind, Randolph S. Marshall, Joanne R. Festa, Philip M. Meyers and E. Sander Connolly Jr.

Object

The object of this study was to report the clinical features, surgical treatment, and long-term outcomes in adults with moyamoya phenomenon treated at a single institution in the US.

Methods

Forty-three adult patients with moyamoya disease (mean age 40 ± 11 years [SD], range 18–69 years) were treated with encephaloduroarteriosynangiosis (EDAS). Neurologists examined patients pre- and postoperatively. Follow-up was obtained in person or by structured telephone interview (median 41 months, range 4–126 months). The following outcomes were collected: transient ischemic attack (TIA), infarction, graft collateralization, change in cerebral perfusion, and functional level according to the modified Rankin scale (mRS). Kaplan-Meier estimates of infarction risk were calculated for comparison of surgically treated and contralateral hemispheres.

Results

The majority of patients were women (65%), were Caucasian (65%), presented with ischemic symptoms (98%), and had bilateral disease (86%). Nineteen patients underwent unilateral and 24 patients bilateral EDAS (67 treated hemispheres). Collateral vessels developed in 50 (98%) of 52 hemispheres for which imaging was available and there was evidence of increased perfusion on SPECT scans in 41 (82%) of the 50 hemispheres evaluated. Periprocedural infarction (< 48 hours) occurred in 3% of the hemispheres treated. In the follow-up period patients experienced 10 TIAs, 6 infarctions, and 1 intracranial hemorrhage. Although the hemisphere selected for surgery was based upon patients' symptoms and severity of pathology, the 5-year infarction-free survival rate was 94% in the surgically treated hemispheres versus < 36% in the untreated hemispheres (p = 0.007). After controlling for age and sex, infarction was 89% less likely to occur in the surgically treated hemispheres than in the contralateral hemispheres (hazard ratio 0.11, 95% CI 0.02–0.56). Thirty-eight (88%) of 43 patients had preserved or improved mRS scores, relative to baseline status.

Conclusions

In this mixed-race population of North American patients, indirect bypass promoted adequate pial collateral development and increased perfusion in the majority of adult patients with moyamoya disease. Patients had low rates of postoperative TIAs, infarction, and hemorrhage, and the majority of patients had preserved or improved functional status.

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Dale Ding, Robert M. Starke, Hideyuki Kano, David Mathieu, 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

Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients.

METHODS

The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs.

RESULTS

A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001).

CONCLUSIONS

Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.

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Robert M. Starke, Dale Ding, Hideyuki Kano, David Mathieu, 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

Pediatric patients (age < 18 years) harboring brain arteriovenous malformations (AVMs) are burdened with a considerably higher cumulative lifetime risk of hemorrhage than adults. Additionally, the pediatric population was excluded from recent prospective comparisons of intervention versus conservative management for unruptured AVMs. The aims of this multicenter, retrospective cohort study are to analyze the outcomes after stereotactic radiosurgery for unruptured and ruptured pediatric AVMs.

METHODS

We analyzed and pooled AVM radiosurgery data from 7 participating in the International Gamma Knife Research Foundation. Patients younger than 18 years of age who had at least 12 months of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no post-radiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes (RIC). The post-radiosurgery outcomes of unruptured versus ruptured pediatric AVMs were compared, and statistical analyses were performed to identify predictive factors.

RESULTS

The overall pediatric AVM cohort comprised 357 patients with a mean age of 12.6 years (range 2.8–17.9 years). AVMs were previously treated with embolization, resection, and fractionated external beam radiation therapy in 22%, 6%, and 13% of patients, respectively. The mean nidus volume was 3.5 cm3, 77% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 59%. The mean radiosurgical margin dose was 21 Gy (range 5–35 Gy), and the mean follow-up was 92 months (range 12–266 months). AVM obliteration was achieved in 63%. During a cumulative latency period of 2748 years, the annual post-radiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 8% and 3%, respectively. Favorable outcome was achieved in 59%. In the multivariate logistic regression analysis, the absence of prior AVM embolization (p = 0.001) and higher margin dose (p < 0.001) were found to be independent predictors of a favorable outcome. The rates of favorable outcome for patients treated with a margin dose ≥ 22 Gy vs < 22 Gy were 78% (110/141 patients) and 47% (101/216 patients), respectively. A margin dose ≥ 22 Gy yielded a significantly higher probability of a favorable outcome (p < 0.001). The unruptured and ruptured pediatric AVM cohorts included 112 and 245 patients, respectively. Ruptured AVMs had significantly higher rates of obliteration (68% vs 53%, p = 0.005) and favorable outcome (63% vs 51%, p = 0.033), with a trend toward a higher incidence of post-radiosurgery hemorrhage (10% vs 4%, p = 0.07). The annual post-radiosurgery hemorrhage rates were 0.8% for unruptured and 1.6% for ruptured AVMs.

CONCLUSIONS

Radiosurgery is a reasonable treatment option for pediatric AVMs. Obliteration and favorable outcomes are achieved in the majority of patients. The annual rate of latency period hemorrhage after radiosurgery for both ruptured and unruptured pediatric AVM patients conveys a significant risk until the nidus is obliterated.

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Jason P. Sheehan, Robert M. Starke, David Mathieu, Byron Young, Penny K. Sneed, Veronica L. Chiang, John Y. K. Lee, Hideyuki Kano, Kyung-Jae Park, Ajay Niranjan, Douglas Kondziolka, Gene H. Barnett, Stephen Rush, John G. Golfinos and L. Dade Lunsford

Object

Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population.

Methods

Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1–223 months).

Results

Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02–1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96–4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score.

Conclusions

Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.