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Allan D. Levi, Robert M. Starke, Ricardo J. Komotar and Robert E. Harbaugh

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Badih Daou, Elias Atallah, Nohra Chalouhi, Robert M. Starke, Jeffrey Oliver, Maria Montano, Pascal Jabbour, Robert H. Rosenwasser and Stavropoula I. Tjoumakaris

OBJECTIVE

The Pipeline embolization device (PED) has become a valuable tool in the treatment of cerebral aneurysms. Although failures with PED treatment have been reported, the characteristics and course of these aneurysms remain a topic of uncertainty.

METHODS

Electronic medical records and imaging studies were reviewed for all patients treated with the PED between July 2010 and March 2015 to identify characteristics of patients and aneurysms with residual filling after PED treatment.

RESULTS

Of 316 cases treated at a single institution, 281 patients had a long-term follow-up. A total of 52 (16.4%) aneurysms with residual filling were identified and constituted the study population. The mean patient age in this population was 58.8 years. The mean aneurysm size was 10.1 mm ± 7.15 mm. Twelve aneurysms were fusiform (23%). Of the aneurysms with residual filling, there were 20 carotid ophthalmic (CO) aneurysms (20% of all CO aneurysms treated), 10 other paraclinoid aneurysms (16.4% of all paraclinoid aneurysms), 7 posterior communicating artery (PCoA) aneurysms (21.9% of all PCoA aneurysms), 7 cavernous internal carotid artery (ICA) aneurysms (14.9% of all cavernous ICA aneurysms), 4 vertebrobasilar (VB) junction aneurysms (14.8% of all VB junction aneurysms), and 3 middle cerebral artery (MCA) aneurysms (25% of all MCA aneurysms). Eleven patients underwent placement of more than one PED (21.2%), with a mean number of devices of 1.28 per case. Eight of 12 aneurysms were previously treated with a stent (15.4%). Nineteen patients underwent re-treatment (36.5%); the 33 patients who did not undergo re-treatment (63.5%) were monitored by angiography or noninvasive imaging. In multivariate analysis, age older than 65 years (OR 2.65, 95% CI 1.33–5.28; p = 0.05), prior stent placement across the target aneurysm (OR 2.94, 95% CI 1.15–7.51; p = 0.02), aneurysm location in the distal anterior circulation (MCA, PCoA, and anterior choroidal artery: OR 2.72, 95% CI 1.19–6.18; p = 0.017), and longer follow-up duration (OR 1.06, 95% CI 1.03–1.09; p < 0.001) were associated with incomplete aneurysm occlusion.

CONCLUSIONS

While the PED can allow for treatment of large, broad-necked aneurysms with high efficacy, treatment failures do occur (16.4%). Aneurysm size, shape, and previous treatment may influence treatment outcome.

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Christoph J. Griessenauer, Robert M. Starke, Paul M. Foreman, Philipp Hendrix, Mark R. Harrigan, Winfield S. Fisher III, Nilesh A. Vyas, Robert H. Lipsky, Mingkuan Lin, Beverly C. Walters, Jean-Francois Pittet and Mali Mathru

OBJECTIVE

Endothelin-1, a potent vasoconstrictor, and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), clinical vasospasm, delayed cerebral ischemia (DCI), and functional outcome following aSAH. In the present study, common endothelin single nucleotide polymorphisms (SNPs) and their relation to aSAH were evaluated.

METHODS

Blood samples from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study were used for genetic evaluation. The CARAS study prospectively enrolled patients with aSAH at 2 academic institutions in the US from 2012 to 2015. Common endothelin SNPs were detected using 5′ exonnuclease (TaqMan) genotyping assays. Analysis of associations between endothelin SNPs and aSAH and its clinical sequelae was performed.

RESULTS

Samples from 149 patients with aSAH and 50 controls were available for analysis. In multivariate logistic regression analysis, the TG (odds ratio [OR] 2.102, 95% confidence interval [CI] 1.048–4.218, p = 0.036) and TT genotypes (OR 7.884, 95% CI 1.003–61.995, p = 0.05) of the endothelin-1 T/G SNP (rs1800541) were significantly associated with aSAH. There was a dominant effect of the G allele (CG/GG genotypes; OR 4.617, 95% CI 1.311–16.262, p = 0.017) of the endothelin receptor A G/C SNP (rs5335) on clinical vasospasm. Endothelin SNPs were not associated with DCI or functional outcome.

CONCLUSIONS

Common endothelin SNPs were found to be associated with presentation with aSAH and clinical vasospasm. Further studies are required to elucidate the relevant pathophysiology and its potential implications in the treatment of patients with aSAH.

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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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Robert M. Starke, Justin M. Cappuzzo, Nicholas J. Erickson and Jonathan H. Sherman

OBJECTIVE

Cystic lesions of the pineal gland are most often uncomplicated benign lesions with typical MRI characteristics. The authors aimed to study pineal lesion characteristics on MRI to better distinguish benign pineal cysts from other pineal region malignancies as well as to determine which characteristics were predictive of the latter malignancies. They also aimed to study risk factors predictive of hydrocephalus or malignancy in patients harboring these lesions.

METHODS

The authors performed a retrospective review of a prospectively compiled database documenting the outcomes of patients with suspected pineal cysts on MRI who had presented in the period from 1998 to 2004. Inherent patient and lesion characteristics were assessed in a univariate logistic regression analysis to predict the following dependent variables: development of hydrocephalus, biopsy-confirmed malignancy, and intervention. Possible inherent patient and lesion characteristics included age, sex, T1 and T2 MRI signal pattern, contrast enhancement pattern, presence of cyst, presence of blood, complexity of lesion, presence of calcification, and duration of follow-up. Inherent patient and lesion characteristics that were predictive in the univariate analysis (p < 0.15) were included in the multivariable logistic regression analysis.

RESULTS

Of the 79 patients with benign-appearing pineal cysts, 26 (33%) were male and 53 (67%) were female, with a median age of 38 years (range 9–86 years). The median cyst radius was 5 mm (range 1–20 mm). Two patients (2.5%) had evidence of calcifications, 7 (9%) had multicystic lesions, and 25 (32%) had some evidence of contrast enhancement.

The median follow-up interval was 3 years (range 0.5–13 years). Seven patients (9%) had an increase in the size of their lesion over time. Eight patients (10%) had a hemorrhage, and 11 patients (14%) developed hydrocephalus. Nine (11%) received ventriculoperitoneal shunts for the development of hydrocephalus, and 12 patients (16%) were found to have malignancies following biopsy or resection. In the multivariate analysis, contrast enhancement on MRI (OR 1.6, 95% CI 2.86–74.74, p = 0.013) and hemorrhage (OR 26.9, 95% CI 3.4–212.7, p = 0.022) were predictive of hydrocephalus. Increasing lesion size and hydrocephalus were near perfect predictors of malignancy and thus were removed from multivariate analysis. In addition, contrast enhancement on MRI (OR 8.8, 95% CI 2.0–38.6, p = 0.004) and hemorrhage (OR 6.8, 95% CI 1.1–40.5, p = 0.036) were predictive of malignancy.

CONCLUSIONS

Although cystic abnormalities of the pineal gland are often benign lesions, they are frequently monitored over time, as other pineal region pathologies may appear similarly on MRI. Patients with growing lesions, contrast enhancement, and hemorrhage on MRI are more likely to develop hydrocephalus and have malignant pathology on histological examination and should therefore be followed up with serial MRI with a lower threshold for neurosurgical intervention.

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Kate A. Hentschel, Badih Daou, Nohra Chalouhi, Robert M. Starke, Shannon Clark, Ashish Gandhe, Pascal Jabbour, Robert Rosenwasser and Stavropoula Tjoumakaris

OBJECTIVE

Mechanical thrombectomy is standard of care for the treatment of acute ischemic stroke. However, limited data are available from assessment of outcomes of FDA-approved devices. The objective of this study is to compare clinical outcomes, efficacy, and safety of non–stent retriever and stent retriever thrombectomy devices.

METHODS

Between January 2008 and June 2014, 166 patients treated at Jefferson Hospital for Neuroscience for acute ischemic stroke with mechanical thrombectomy using Merci, Penumbra, Solitaire, or Trevo devices were retrospectively reviewed. Primary outcomes included 90-day modified Rankin Scale (mRS) score, recanalization rate (thrombolysis in cerebral infarction [TICI score]), and incidence of symptomatic intracranial hemorrhages (ICHs). Univariate analysis and multivariate logistic regression determined predictors of mRS Score 3–6, mortality, and TICI Score 3.

RESULTS

A total of 99 patients were treated with non–stent retriever devices (Merci and Penumbra) and 67 with stent retrievers (Solitaire and Trevo). Stent retrievers yielded lower 90-day NIH Stroke Scale scores and higher rates of 90-day mRS scores ≤ 2 (22.54% [non–stent retriever] vs 61.67% [stent retriever]; p < 0.001), TICI Score 2b–3 recanalization rates (79.80% [non–stent retriever] vs 97.01% [stent retriever]; p < 0.001), percentage of parenchyma salvaged, and discharge rates to home/rehabilitation. The overall incidence of ICH was also significantly lower (40.40% [non–stent retriever] vs 13.43% [stent retriever]; p = 0.002), with a trend toward lower 90-day mortality. Use of non–stent retriever devices was an independent predictor of mRS Scores 3–6 (p = 0.002), while use of stent retrievers was an independent predictor of TICI Score 3 (p < 0.001).

CONCLUSIONS

Stent retriever mechanical thrombectomy devices achieve higher recanalization rates than non–stent retriever devices in acute ischemic stroke with improved clinical and radiographic outcomes and safety.

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Badih Daou, Edison P. Valle-Giler, Nohra Chalouhi, Robert M. Starke, Stavropoula Tjoumakaris, David Hasan, Robert H. Rosenwasser, Ryan Hebert and Pascal Jabbour

OBJECTIVE

The Pipeline Embolization Device (PED) has become an effective treatment strategy for some cerebral aneurysms. Concerns regarding the patency of branch arteries have been raised. The objective of this study was to assess the patency of the posterior communicating artery (PCoA) following treatment of PCoA aneurysms using the PED.

METHODS

All patients with PCoA aneurysms treated with the PED who had angiographic follow-up were retrospectively identified. The patency of the PCoA at follow-up was evaluated by 2 authors who were not involved in the intervention. Univariate and multivariate analyses were performed to identify factors associated with the following: 1) PCoA patency versus no or diminished flow, and 2) PCoA patency and diminished flow versus PCoA occlusion.

RESULTS

Thirty patients with an angiographic follow-up of 6 months were included. Aneurysm obliteration was achieved in 25 patients (83.3%). The PCoA was patent in 7 patients (23.3%), had diminished flow in 7 patients (23.3%), and was occluded in 16 patients (53.3%). In the univariate analysis of outcome, there was a trend for aneurysms with incomplete occlusion, aneurysms not previously treated, those with presence of a fetal PCoA, and those with an artery coming from the aneurysm to have higher odds of the PCoA remaining patent. In univariate and multivariate analyses of factors associated with outcome, fetal PCoA and presence of an artery coming from the aneurysm were associated with the PCoA remaining open with or without diminished flow. No patients had symptoms related to PCoA occlusion.

CONCLUSIONS

Occlusion and diminished flow through the PCoA is common following PED treatment of PCoA aneurysms. However, it is clinically insignificant in most cases.

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Michael Kerin Morgan, Marcus Andrew Stoodley and John William Fuller

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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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Badih Daou, Nohra Chalouhi, Robert M. Starke, Guilherme Barros, Lina Ya'qoub, John Do, Stavropoula Tjoumakaris, Robert H. Rosenwasser and Pascal Jabbour

OBJECTIVE

With the increasing number of aneurysms treated with endovascular coiling, more recurrences are being encountered. The aim of this study was to evaluate the efficacy and safety of microsurgical clipping in the treatment of recurrent, previously coiled cerebral aneurysms and to identify risk factors that can affect the outcomes of this procedure.

METHODS

One hundred eleven patients with recurrent aneurysms whose lesions were managed by surgical clipping between January 2002 and October 2014 were identified. The rates of aneurysm occlusion, retreatment, complications, and good clinical outcome were retrospectively determined. Univariate and multivariate logistic regressions were performed to identify factors associated with these outcomes.

RESULTS

The mean patient age was 50.5 years, the mean aneurysm size was 7 mm, and 97.3% of aneurysms were located in the anterior circulation. The mean follow-up was 22 months. Complete aneurysm occlusion, as assessed by intraoperative angiography, was achieved in 97.3% of aneurysms (108 of 111 patients). Among patients, 1.8% (2 of 111 patients) had a recurrence after clipping. Retreatment was required in 4.5% of patients (5 of 111) after clipping. Major complications were observed in 8% of patients and mortality in 2.7%. Ninety percent of patients had a good clinical outcome. Aneurysm size (OR 1.4, 95% CI 1.08–1.7; p = 0.009) and location in the posterior circulation were significantly associated with higher complications. All 3 patients who had coil extraction experienced a postoperative stroke. Aneurysm size (OR 1.2, 95% CI 1.02–1.45; p = 0.025) and higher number of interventions prior to clipping (OR 5.3, 95% CI 1.3–21.4; p = 0.019) were significant predictors of poor outcome. An aneurysm size > 7 mm was a significant predictor of incomplete obliteration and retreatment (p = 0.018).

CONCLUSIONS

Surgical clipping is safe and effective in treating recurrent, previously coiled cerebral aneurysms. Aneurysm size, location, and number of previous coiling procedures are important factors to consider in the management of these aneurysms.