Cigarette smoking and risk of intracranial aneurysms in middle-aged women.

BACKGROUND AND PURPOSE: We previously reported a single-centre study demonstrating that smoking confers a six-fold increased risk for having an unruptured intracranial aneurysm (UIA) in women aged between 30 and 60 years and this risk was higher if the patient had chronic hypertension. There are no data with greater generalisability evaluating this association. We aimed to validate our previous findings in women from a multicentre study. METHODS: A multicentre case-control study on women aged between 30 and 60 years, that had magnetic resonance angiography (MRA) during the period 2016-2018. Cases were those with an incidental UIA, and these were matched to controls based on age and ethnicity. A multivariable conditional logistic regression was conducted to evaluate smoking status and hypertension differences between cases and controls. RESULTS: From 545 eligible patients, 113 aneurysm patients were matched to 113 controls. The most common reason for imaging was due to chronic headaches in 62.5% of cases and 44.3% of controls. A positive smoking history was encountered in 57.5% of cases and in 37.2% of controls. A multivariable analysis demonstrated a significant association between positive smoking history (OR 3.7, 95%CI 1.61 to 8.50), hypertension (OR 3.16, 95% CI 1.17 to 8.52) and both factors combined with a diagnosis of an incidental UIA (OR 6.9, 95% CI 2.49 to 19.24). CONCLUSIONS: Women aged between 30 and 60 years with a positive smoking history have a four-fold increased risk for having an UIA, and a seven-fold increased risk if they have underlying chronic hypertension. These findings indicate that women aged between 30 and 60 years with a positive smoking history might benefit from a screening recommendation.

Systemic Inflammatory Response Syndrome and Outcomes in Intracerebral Hemorrhage.

BACKGROUND: To identify the patients at greatest odds for systemic inflammatory response syndrome (SIRS) and examine the association between SIRS and outcomes in patients presenting with intracerebral hemorrhage (ICH). METHODS: We retrospectively reviewed consecutive patients presenting to a tertiary care center from 2008 to 2013 with ICH. SIRS was defined according to standard criteria as 2 or more of the following: (1) body temperature <36 or >38 °C, (2) heart rate >90 beats per minute, (3) respiratory rate >20, or (4) white blood cell count <4000/mm(3) or >12,000/mm(3) or >10 % polymorphonuclear leukocytes for >24 h in the absence of infection. The outcomes of interest, discharge modified Rankin Scale (mRS 4-6), death, and poor discharge disposition (discharge anywhere but home or inpatient rehab) were assessed using logistic regression. RESULTS: A total of 249 ICH patients met inclusion criteria and 53 (21.3 %) developed SIRS during their hospital stay. A score was developed (ranging from 0 to 3) to identify patients at greatest risk for developing SIRS. Adjusting for stroke severity, SIRS was associated with mRS 4-6 (OR 5.25, 95 %CI 2.09-13.2) and poor discharge disposition (OR 3.74, 95 %CI 1.58-4.83) but was not significantly associated with death (OR 1.75, 95 %CI 0.58-5.32). We found that 33 % of the effect of ICH score on poor functional outcome at discharge was explained by the development of SIRS in the hospital (Sobel 2.11, p = 0.03). CONCLUSION: We observed that approximately 20 % of patients with ICH develop SIRS, and that patients with SIRS were at increased risk of having poor functional outcome at discharge.

Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults.

Reovirus, an oncolytic RNA virus exhibiting antiglioma activity, was shown in a previous single institution phase 1 study found that the inoculation of the virus to be well tolerated in patients with recurrent malignant glioma (MG). The goals of multicenter study reported herein were to determine the dose-limiting toxicity, maximum tolerated dose, and target lesion response rate when reovirus was administered in a novel fashion via intratumoral infusion for 72 hours in patients with recurrent malignant glioma. Fifteen adult patients were treated in a dose escalation study ranging from 1 × 10(8) to 1 × 10(10) tissue culture infectious dose 50, tentimes the dose achieved in the previous trial. Neurological, functional examinations, and imaging studies were completed pre- and postinfusion. There was one grade 3 adverse event (convulsions) felt to be possibly related to treatment, but no grade 4 adverse events considered probably or definitely related to treatment. Dose-limiting toxicity were not identified and a maximum tolerated dose was not reached. Evidence of antiglioma activity was seen in some patients. This first report of intratumoral infusion of reovirus in patients with recurrent malignant glioma demonstrated the approach to be safe and well tolerated, warranting further studies.

Contrast conservation measures during the global iohexol contrast shortage crisis did not affect stroke thrombectomy outcomes.

BACKGROUND: The current global shortage in iohexol contrast material (Omnipaque) used in performing CT-based triage images and mechanical thrombectomy (MT) represents a challenge to the healthcare system. A study was undertaken to assess the safety and feasibility of implementing protocol-based changes in pre-MT and MT workflow at a comprehensive stroke center. METHODS: A retrospective cohort study was undertaken of all patients with stroke who underwent MT during a 3-week period before implementing the contrast shortage protocol and for 3 weeks while implementing the protocol. The contrast shortage protocol included not performing perfusion images for MT selection and using diluted iohexol (50% contrast mixed with 50% heparinized saline) during the MT procedure. Procedural variables were compared between the two groups. RESULTS: A total of 27 patients underwent MT during the study period, 12 pre-contrast shortage and 15 post-contrast shortage. The average contrast volume used during the MT procedure was reduced from 83 mL to 68 mL after implementing the contrast shortage protocol (p=0.04). No difference was noted in the rate of successful reperfusion (11/15 vs 10/12), average time to recanalization (21 vs 23 min), average radiation dose (1143 vs 1117mGy) and time under fluoroscopy (20.7 vs 20.5 min) in the pre- and post-contrast shortage groups. A favorable discharge outcome was observed in 3/12 patients and 4/15 patients in the pre- and post-shortage periods, respectively (p=0.92). CONCLUSIONS: Modifying stroke workflow to adapt to the current global shortage in iohexol is feasible. Using diluted iohexol (50% contrast mixed with 50% heparinized saline) did not affect MT outcomes.

Case-Control Study Design in Neurological Surgery.

The hallmark of case-control study design involves dividing groups based on outcome and looking back at exposures to determine associations. Case-control studies are ideal for scenarios when outcomes are rare, making them well suited to the infrequent events often found among neurosurgical diseases. It is also a favorable design for scenarios when it would be infeasible or unethical to assign treatment groups as is necessary for a randomized controlled trial. Case-control studies are powerful but often misapplied and mislabeled. This article provides an overview of case-control study design along with discussion of a real-world example of an effectively executed case-control study.

Role of aspirin and statin therapy in patients with cerebral cavernous malformations.

Stagnant blood flow and organizing thrombus are intralesional components of patients with cerebral cavernous malformations (CCM). Stasis and inflammation are mechanisms of growth, lesional instability and acute hemorrhages with or w/o symptoms. We evaluate the association of pre-diagnostic aspirin and/or statin use with acute hemorrhages at diagnosis. Patients with a CCM diagnosis were identified and categorized according to their medications on admission into four groups (no therapy, statin, aspirin, combined). The primary outcome was an acute hemorrhage (with or w/o symptoms) at diagnosis reported in a standardized manner from the T2 weighted magnetic resonance image. A multivariate generalized linear mixed models (GLMM) was utilized to conduct per-lesion analysis. We identified 446 patients with 635 lesions. An acute hemorrhage at diagnosis was observed in 31% of the patients. There were 328 patients without statin or aspirin therapy, 34% of whom presented with acute hemorrhage. Of patients on aspirin therapy at diagnosis, 25% presented with hemorrhage. Of patients on statin therapy, 26% had a hemorrhage at diagnosis. Combined therapy in 44 patients demonstrated a lower proportion of patients with acute hemorrhages (7 patients, 16% incidence). A GLMM showed that patients in the combined therapy group to have significantly lower odds of having an acute hemorrhage at diagnosis compared to the reference group of no therapy (OR 0.24; 95% CI 0.09-0.59; P = 0.002). Patients with a CCM receiving therapy with both aspirin and statins were less likely to present at diagnosis with acute hemorrhage.

Women With First-Hand Tobacco Smoke Exposure Have a Higher Likelihood of Having an Unruptured Intracranial Aneurysm Than Nonsmokers: A Nested Case-Control Study.

BACKGROUND: The prevalence of unruptured intracranial aneurysms (UIA) in females who smoke cigarettes and the association between smoking and hypertension with purely incidental UIAs have been unexplored. OBJECTIVE: To obtain the prevalence of UIA among females and to assess the relationship between smoking and hypertension with a diagnosis of incidental UIAs. METHODS: A nested case-control study from a cohort of female patients aged between 30 and 60 yr with a brain magnetic resonance angiography (MRA) between 2016 and 2018. Incidental UIAs were compared to patients with normal MRAs. Smoking was characterized as never or former/current smokers. A logistic regression was used to evaluate the association between smoking, hypertension, or both, with a diagnosis of incidental UIAs. RESULTS: A total of 1977 patients had a brain MRA between 2016 and 2018. From 1572 nonsmoker patients, we encountered 30 with an UIA (prevalence: 1.9%). There were 405 patients with a positive smoking history, and 77 patients harbored an UIA (prevalence: 19%). Of 64 aneurysm patients and 130 random controls eligible for the case control, aneurysm patients were more likely to have a positive smoking history and hypertension compared with healthy controls (60% vs 18%, P ≤ .001; 44% vs 14%, P ≤ .001). A multivariable analysis demonstrated a significant association between a smoking history, hypertension, or both factors with an incidental UIA (odds ratio [OR] 5.8 CI 1.22-11.70; OR 3.8 CI 2.31-14.78; OR 12.6 CI 4.38-36.26; respectively). CONCLUSION: Females who smoke cigarettes have a higher prevalence of UIAs than the general population. Smoking confers a higher risk for having a silent UIA, aggravated by hypertension. This population is an ideal target for potential screening.

Flow Diversion for Treatment of Partially Thrombosed Aneurysms: A Multicenter Cohort.

BACKGROUND: Partially thrombosed intracranial aneurysms (PTIA) represent a unique subset of intracranial aneurysms with an ill-defined natural history, posing challenges to standard management strategies. This study aims to assess the efficacy of flow diversion in the treatment of this pathology. METHODS: A retrospective review of patients with flow-diverted PTIA at 6 cerebrovascular centers was performed. Clinical and radiographic data were collected from the medical records, with the primary outcome of aneurysmal occlusion and secondary outcomes of clinical status and complications. RESULTS: Fifty patients with 51 PTIA treated with flow diversion were included. Median age was 56.5 years. Thirty-three (64.7%) aneurysms were saccular and 16 (31.4%) were fusiform/dolichoectatic. The most common location was the internal carotid artery (54.9%) followed by the vertebral and basilar arteries (17.7% and 17.7%, respectively). Last imaging follow-up was performed at a median of 25.1 (interquartile range, 12.8-43) months. Complete occlusion at last radiographic follow-up was achieved in 37 (77.1%) aneurysms. Pretreatment aneurysm thrombosis of >50% was associated with a significantly lower rate of complete aneurysm occlusion (58.8 vs. 87.1%, P = 0.026) with a trend toward better functional outcome (modified Rankin scale <2) at last follow-up in patients with <50% pretreatment aneurysm thrombosis (96.8 vs. 82.4; P = 0.08). Ischemic complications occurred in 5 (9.8%) patients, producing symptoms in 4 (7.8%) and resultant mortality in 2 (4.2%) patients. CONCLUSIONS: Flow diversion treatment of PTIA has adequate efficacy along with a reasonable safety profile. Aneurysms harboring large amounts of pretreatment thrombus were associated with lower rates of complete occlusion.

Role of the Neurosurgeon in Acute Ischemic Stroke Treatment From Triage to Intensive Care Unit.

As ischemic stroke care advances with more patients eligible for mechanical thrombectomy, so too does the role of the neurosurgeon in these patients. Neurosurgeons are an important member of the team from triage through the intensive care unit. This paper explores current research and insights on the contributions of neurosurgeons in care of acute ischemic stroke patients in the acute setting.

Microsurgical resection of a medullary cavernous malformation through a far lateral approach.

The decision to resect a cavernous malformation of the brainstem is based on patient- and lesion-specific factors. The patient's age, comorbidities, neurologic condition, and number and severity of symptomatic hemorrhages are crucial to consider.1,3,5 The proximity to the brainstem surface, amount of hematoma, and true lesion size help dictate the surgical corridor.2,4 We present a patient with a medullary cavernous malformation who had three hemorrhages and neurologic worsening. The surgical approach was based on detailed preoperative imaging. We performed a far lateral posterior fossa exposure to resect the lesion. The details of surgical planning and the microsurgery are presented. The video can be found here: https://youtu.be/2y-OJ22Zjw8.

What is a Case-Control Study?

Case-control (case-control, case-controlled) studies are beginning to appear more frequently in the neurosurgical literature. They can be more robust, if well designed, than the typical case series or even cohort study to determine or refine treatment algorithms. The purpose of this review is to define and explore the differences between case-control studies and other so-called nonexperimental, quasiexperimental, or observational studies in determining preferred treatments for neurosurgical patients.

Coil Embolization of a Carotid-Cavernous Fistula Through Superior Ophthalmic Venous Access via External Jugular Vein Puncture Approach.

Carotid-cavernous fistulas are vascular malformations that pose a risk for intracranial hemorrhage when there is documented cortical venous drainage. When possible, treatment with transvenous embolization has become the technique of choice since the late 1990s.1,2 We present a case of a patient with a carotid-cavernous fistula treated with venous coil embolization via a jugular venous approach. The patient was a 59-year-old female with a history of intense headaches. Initial magnetic resonance imaging showed congestion in the right cavernous sinus, and a diagnostic angiogram revealed a cavernous carotid fistula Thomas type 4.3,4 Given the presence of retrograde cortical venous drainage, we decided to treat the lesion. A femoral route for endovascular treatment was attempted, but it was unsuccessful in traversing the external jugular vein due to venous valves. We accessed the fistula through a direct puncture direct proximal approach,5 from the external jugular vein making our trajectory through the facial-angular-supraorbital vein, ultimately reaching the cavernous sinus. We then filled the sinus with coils to obliterate the fistula. The patient awakened neurologically intact, and a postoperative angiogram demonstrated complete occlusion of the lesion. The patient was discharged at postoperative day 1 without complications. In this video, we narrate the important details of this alternative when a traditional route is inaccessible (Video 1). Informed consent was obtained for the case illustrated; however, neither Institutional Review Board nor patient consent is required for the report of a single case in which no identifiable patient information is shared.

What Isn't a Case-Control Study?

BACKGROUND: Confusion exists among neurosurgeons when choosing and implementing an appropriate study design and statistical methods when conducting research. We noticed particular difficulty with mislabeled and inappropriate case-control studies in the neurosurgical literature. OBJECTIVE: To quantify and to rigorously review this issue for appropriateness in publication and to establish quality of the manuscripts using a rigorous technique. METHODS: Following a literature search, pairs drawn from 5 independent reviewers evaluated a complete sample of 125 manuscripts claiming to be case-control studies with respect to basic case-control criteria. Seventy-five papers were then subjected to a more rigorous appraisal for quality using the SIGN Methodology Checklist for case-control studies. RESULTS: Fifty publications were rejected based on basic criteria used to identify case-control design. Of the 75 subjected to quality analysis, 46 were felt to be acceptable for publication. Only 11 papers (9%) achieved the designation of high quality. Of the original 125 papers evaluated, 79 (63%) were inappropriately labeled case-control studies. CONCLUSION: Mislabeling and use of inappropriate study design are common in the neurosurgical literature. Manuscripts should be evaluated rigorously by reviewers and readers, and neurosurgical training programs should include instruction on choice of appropriate study design and critical appraisal of the literature.

Endovascular Trapping of Large Cervical Carotid Pseudoaneurysm in Marfan Syndrome Presenting with Progressive Respiratory Distress.

BACKGROUND: Isolated cervical pseudoaneurysms of the internal carotid artery (ICA) in patients with Marfan syndrome are extremely rare. CASE DESCRIPTION: A 73-year-old female with Marfan syndrome and history of multiple aortic aneurysms presented to an outside hospital with dysphagia, a mass in her neck, dizziness, nausea, and vomiting. A computed tomography angiogram showed bilateral cervical ICA pseudoaneurysms, more significant on the right side. A laryngoscopy demonstrated edematous vocal cords and a significant mass effect on the right side. She suffered from significant respiratory distress and aspiration, for which she had to be intubated and transferred to our institution for definitive care. The patient was taken for angiography for carotid artery test occlusion and endovascular trapping with coils and onyx embolization of the carotid pseudoaneurysm. The hospital course was complicated with femoral closure device failure, leading to groin hematoma, pneumonia, and respiratory failure requiring tracheostomy and percutaneous endoscopic gastrostomy. The patient was discharged to rehabilitation 34 days after admission. Stable exclusion of the large right pseudoaneurysm was observed at 3 months' follow-up with computed tomography angiography, as well as significant improvement in the last clinical follow-up obtained 6 months after the procedure. CONCLUSION: Pseudoaneurysms of the cervical ICA associated with Marfan syndrome are rare. Carotid test occlusion and endovascular permanent embolization are possible in a patient with life-threatening symptoms. Cautious use of vascular closure devices, especially collagen plug-based ones, are required in such patients, given their abnormal extracellular matrix structure.

Proposal of a Grading System for Predicting Discharge Mortality and Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Several outcome prediction systems have been developed to evaluate aneurysmal subarachnoid hemorrhage (aSAH). However, they can be difficult to use and can contain subjective elements. We sought to identify the predictors of aSAH outcomes at discharge to provide an accurate and reliable scoring system. METHODS: A retrospective cohort study of patients with aSAH at an academic institution from 2007 to 2016 was conducted. The primary outcome measure was the modified Rankin scale (mRS) score at discharge, with mRS scores of 0-2 considered favorable and mRS scores of 3-6 considered unfavorable. Factors significant on multivariate regression were used to develop a scale, which was compared with other established grading systems using receiver operating characteristic curves. RESULTS: We identified 279 patients with aSAH, 37.3% of whom had unfavorable outcomes. The proposed scale assigns 2 points for postresuscitation Glasgow coma scale score of ≤8, 1 point for age ≥70 years, 1 for antiplatelet therapy on admission, and 1 for SAH thickness of ≥10 mm, with a total score of 0-5. The proposed, Subarachnoid Hemorrhage International Trialists, and Hunt and Hess scales had similar areas under the curve (85.2%, 84.8%, and 80.6%, respectively; P > 0.05) but were significantly better than the World Federation of Neurological Surgeons (78.5%; P = 0.001) and modified Fisher (60.8%; P < 0.001) scales. CONCLUSION: We propose a grading scale to predict discharge mortality and functional outcomes in patients with aSAH. The proposed scale outperformed most other outcome prediction scales. The proposed scale contains objective elements, is easy to apply by memory, and can be a useful and effective measure to predict aSAH outcomes.

Predictors of Nasoseptal Flap Use After Endoscopic Transsphenoidal Pituitary Mass Resection.

OBJECTIVE: The pedicled nasoseptal flap (NSF) is the widely accepted reconstructive technique of choice for repair of larger skull base defects after endoscopic endonasal approaches. There is a dearth of literature examining the decision-making process regarding flap harvest. The objective of this study is to evaluate preoperative characteristics that predict the use of NSF reconstruction after endoscopic transsphenoidal resection of pituitary tumors. METHODS: In this retrospective case control study, demographic, clinical, imaging, and procedural details were gathered on all patients undergoing endoscopic transsphenoidal pituitary adenoma resection at a single academic center since January 2009. Characteristics were compared for patients receiving an NSF and those not undergoing NSF repair. A multivariate model that best predicted the use of an NSF was built and a risk score was developed. RESULTS: Two hundred thirty-eight patients were included, and 39 underwent NSF placement. Tumor size and anatomic characteristics were the predominant factors that significantly differed between cases and controls. Patients with transsellar tumor extension had 6.3 higher odds of requiring NSF, each millimeter increase in tumor height on coronal T1 magnetic resonance imaging increased the odds of NSF use by 1.2. The flap risk score (FRS) is calculated by adding tumor height (mm) to 6 if there is transsellar extension. At an FRS of >35, the FRS is 87% specific and 85% sensitive for flap placement. CONCLUSIONS: Preoperative imaging characteristics can predict NSF use. The FRS can be applied by surgical teams and referring physicians to determine which patients are more likely to undergo NSF repair.

Seizure outcomes after stereotactic radiosurgery for the treatment of cerebral arteriovenous malformations.

OBJECTIVE Patients with cerebral arteriovenous malformations (AVMs) commonly present with seizure. Seizure outcomes in patients treated with stereotactic radiosurgery (SRS) are poorly defined. A case series of patients with cerebral AVMs treated with SRS is presented to evaluate long-term seizure outcome. METHODS A retrospective review of the medical record was performed, identifying 204 consecutive patients with AVMs treated with SRS between January 1991 and June 2012. Clinical and radiographic data were evaluated. Seizure outcome was measured using the Engel Epilepsy Surgery Outcome Scale. Mean duration of follow-up was 37.1 months (SD 38.3 months) with a minimum follow-up period of 1 month. RESULTS Of the 204 patients with cerebral AVMs treated with SRS, 78 patients (38.2%) presented with seizures and 49 of those patients were treated with antiepileptic drugs (AEDs). Following SRS, 63 (80.8%) of the 78 patients who had had seizures prior to SRS were seizure-free at a mean follow-up time of 37.2 months (SD 41.3 months). Of the 49 patients who had been treated with AEDs, 17 were still taking AEDs at last follow-up. Of the 126 patients who did not present with seizures prior to treatment with SRS, only 5 patients (4.0%) had seizures in the post-SRS period. There was no significant correlation between post-SRS seizure status and patient demographic features, comorbidities, AVM characteristics, history of operative intervention, pre- or posttreatment hemorrhage, or radiographic degree of AVM resolution. CONCLUSIONS Stereotactic radiosurgery for treatment of cerebral AVMs is effective at providing long-term control of seizures. A substantial number of patients who were treated with SRS were not only seizure free at their last follow-up, but had been successfully weaned from antiepileptic medications.

Reliability assessment of the Biffl Scale for blunt traumatic cerebrovascular injury as detected on computer tomography angiography.

OBJECTIVE Blunt traumatic cerebrovascular injury (TCVI) represents structural injury to a vessel due to high-energy trauma. The Biffl Scale is a widely accepted grading scheme for these injuries that was developed using digital subtraction angiography. In recent years, screening CT angiography (CTA) has been used to identify patients with TCVI. The reliability of this scale, with injuries assessed using CTA, has not yet been determined. METHODS Seven independent raters, including 2 neurosurgeons, 2 neuroradiologists, 2 neurosurgical residents, and 1 neurosurgical vascular fellow, independently reviewed each presenting CTA of the neck performed in 40 patients with confirmed TCVI and assigned a Biffl grade. Ten images were repeated to assess intrarater reliability, for a total of 50 CTAs. Fleiss' multirater kappa (κ) and interclass correlation were calculated as a measure of interrater reliability. Weighted Cohen's κ was used to assess intrarater reliability. RESULTS Fleiss' multirater κ was 0.65 (95% CI 0.61-0.69), indicating substantial agreement as to the Biffl grade assignment among the 7 raters. Interclass correlation was 0.82, demonstrating excellent agreement among the raters. Intrarater reliability was perfect (weighted Cohen's κ = 1) in 2 raters, and near perfect (weighted Cohen's κ > 0.8) in the remaining 5 raters. CONCLUSIONS Grading of TCVI with CTA using the Biffl Scale is reliable.

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.