Delayed Iatrogenic Direct Carotid Cavernous Fistula Following Flow Diversion for Aneurysm With Spontaneous Healing: A Case Report.

An abnormal connection between the carotid artery and cavernous sinus is referred to as a carotid cavernous fistula (CCF). A direct CCF results when the connection occurs between the intracranial internal carotid artery (ICA) and the cavernous sinus. These events are typically the result of a head injury, but can also be iatrogenic, resulting from various intracranial procedures. Direct CCF occurrences rarely heal spontaneously due to the high flow rate across the fistula. In this report, we present an uncommon case involving a delayed iatrogenic direct CCF, which developed following the placement of a pipeline flow-diverting stent that was used to treat a cerebral aneurysm. Interestingly, this unusual iatrogenic direct CCF subsequently spontaneously resolved within a few months. To our knowledge, this is the only case of a delayed CCF occurring with the use of a flow-diverting sent, which then resolved on its own. This report recounts our experience with the case.

Hemorrhagic Pilocytic Astrocytomas in Adults: A Case Report and Literature Review.

Pilocytic astrocytomas are histologically benign tumors, generally found in the pediatric population. Onset of symptoms is generally insidious, predominantly stemming from mass effect upon nearby structures. Patients harboring a pilocytic astrocytoma may present with gait disturbance, headaches, cranial nerve deficits, as well as hydrocephalus, depending on the exact location. Although cases of adult pilocytic astrocytomas in the adult population are described, they are quite uncommon. We present a case of an adult female presenting with acute neurological compromise resulting from an acutely hemorrhagic posterior fossa pilocytic astrocytoma. Her initial neurological assessment was consistent with a Glasgow coma scale of 4T, as the patient was experiencing decerebrate posturing. An emergent external ventricular drain was placed in the emergency department for acute hydrocephalus as a temporizing measure, prior to evacuation of the associated subdural and intratumoral hemorrhages, as well as resection of the mass. After a long hospital course and extensive rehabilitation, the patient made a remarkable recovery and eventually gave birth to a child via Caesarean section three years after her initial presentation.

Primary Angioplasty Versus Stenting for Endovascular Management of Intracranial Atherosclerotic Disease Following Acute Ischemic Stroke.

BACKGROUND: The future of neuroendovascular treatment for intracranial atherosclerotic disease (ICAD) has been debated since the results of SAMMPRIS reflected poor outcomes following endovascular therapy. There is currently a large spectrum of current management strategies. We compared historical outcomes of patients with ICAD and stroke that were treated with angioplasty-alone versus stent placement. METHODS: We extracted a population from the Nationwide Inpatient Sample (NIS) (2005-2011) and the National Inpatient Sample (NIS) (2012) composed of patients with ICAD and infarction that were admitted nonelectively and received endovascular revascularization. Patients treated with thrombectomy or thrombolysis were excluded. Categorical variables were compared with Chi-squared tests. Binary logistic regression was performed to evaluate mortality while controlling for age, sex, severity, and comorbidities. RESULTS: About 2059 admissions met our criteria. A majority were treated via stent placement (71%). Angioplasty-alone had significantly higher mortality (17.6% vs. 8.4%, P<0.001), but no difference in iatrogenic stroke rate (3.4% vs. 3.6%, P=0.826), compared to stent placement. The adjusted odds ratio of mortality for stented patients was 0.536 (95% CI: 0.381-0.753, P<0.001) in comparison to patients treated with angioplasty alone. CONCLUSIONS: This study found the risk of mortality to be elevated following angioplasty alone in comparison to revascularization with stent placement, without a corresponding significant difference in iatrogenic stroke rate. This may represent selection bias due to patient characteristics not defined in the database, but it also may indicate that patients with ICAD and acute stroke have increased odds of stenosis that is refractory to angioplasty alone and have a high risk of mortality without revascularization.

Trends in mortality following mechanical thrombectomy for the treatment of acute ischemic stroke in the USA.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) for the treatment of acute ischemic stroke has been growing in popularity while the therapeutic benefit of MT has been increasingly debated. Our objective was to examine national trends in mortality following MT. METHODS: We analyzed the National Inpatient Sample (2012) and the Nationwide Inpatient Sample (2008-2011) for patients with a primary diagnosis of acute ischemic stroke that received MT. Temporal trends in mortality were examined using Spearman's rank correlation. To account for confounding factors, mortality was further analyzed in binary logistic regression. RESULTS: Hospitals performing MT comprised 8% of all hospitals treating ischemic stroke. The percentage of stroke cases treated with MT increased from 0.6% of cases in 2008 to 1.1% in 2012, totaling 16 307 MT cases in a 5 year period. Inhospital mortality decreased over the study period from 25.4% in 2008 to 16.1% in 2012 (r=-0.081, p<0.001). This finding was supported by regression analysis as each incremental year reduced the odds of mortality by 20% (OR=0.832, p<0.001). Administration of recombinant tissue plasminogen activator was associated with a decrease in the odds of mortality (OR=0.805, p<0.001). CONCLUSIONS: Utilization of MT represents a small percentage of stroke cases, although the trend is increasing. Mortality following MT has been showing a steady decline over the past 5 years. This may be a result of a learning curve, improved patient selection, and/or device improvements. Randomized trials remain essential to evaluate the potential benefit of endovascular devices and identify the most appropriate patients.

Carotid Artery Stenosis with Acute Ischemic Stroke: Stenting versus Angioplasty.

BACKGROUND: When a patient with carotid artery stenosis presents emergently with acute ischemic stroke, the optimum treatment plan is not clearly defined. If intervention is warranted, and open surgery is prohibitive, endovascular revascularization may be performed. The use of stents places the patient at additional risk due to their thrombogenic potential. The intent of this study was to compare outcomes following endovascular approaches (angioplasty alone vs. stent) in the setting of acute stroke. METHODS: We extracted a population from the National Inpatient Sample (2012) and the Nationwide Inpatient Sample (2003-2011) composed of patients with carotid artery stenosis with infarction that were admitted nonelectively and received endovascular revascularization. Patients treated with mechanical thrombectomy or thrombolysis were excluded. Categorical variables were compared between treatment groups with Chi-squared tests. Binary logistic regression was performed to evaluate mortality and iatrogenic stroke while controlling for age, case severity, and comorbidity burden. RESULTS: About 6,333 admissions met our criteria. A majority were treated via stenting (89%, n = 5,608). The angioplasty-alone group had significantly higher mortality (9.0% vs. 3.8%, p < 0.001) and iatrogenic stroke rate (3.9% vs. 1.9%, p < 0.001) than the stent group. The adjusted odds ratios of mortality and iatrogenic stroke for patients treated with angioplasty alone were 1.953 (p < 0.001) and 1.451 (p = 0.105), respectively, in comparison to patients treated with carotid stenting. CONCLUSION: Multivariate analysis found the risk of mortality to be elevated following angioplasty alone. This may represent selection bias, but it also may indicate that symptomatic patients with stroke suffer from severe stenosis and unstable plaques that would benefit from stent placement. These results would caution angioplasty alone as an arm of a future randomized trial involving this severely burdened patient population requiring urgent intervention.

Minimally Invasive Thumb-sized Pterional Craniotomy for Surgical Clip Ligation of Unruptured Anterior Circulation Aneurysms.

Less invasive surgical approaches for intracranial aneurysm clipping may reduce length of hospital stay, surgical morbidity, treatment cost, and improve patient outcomes. We present our experience with a minimally invasive pterional approach for anterior circulation aneurysms performed in a major tertiary cerebrovascular center and compare the results with an aged matched dataset from the Nationwide Inpatient Sample (NIS). From August 2008 to December 2012, 22 elective aneurysm clippings on patients ≤55 years of age were performed by the same dual fellowship-trained cerebrovascular/endovascular neurosurgeon. One patient (4.5%) experienced transient post-operative complications. 18 of 22 patients returned for follow-up imaging and there were no recurrences through an average duration of 22 months. A search in the NIS database from 2008 to 2010, also for patients aged ≤55 years of age, yielded 1,341 hospitalizations for surgical clip ligation of unruptured cerebral aneurysms. Inpatient length of stay and hospital charges at our institution using the minimally invasive thumb-sized pterional technique were nearly half that of NIS (length of stay: 3.2 vs 5.7 days; hospital charges: $52,779 vs. $101,882). The minimally invasive thumb-sized pterional craniotomy allows good exposure of unruptured small and medium-sized supraclinoid anterior circulation aneurysms. Cerebrospinal fluid drainage from key subarachnoid cisterns and constant bimanual microsurgical techniques avoid the need for retractors which can cause contusions, localized venous infarctions, and post-operative cerebral edema at the retractor sites. Utilizing this set of techniques has afforded our patients with a shorter hospital stay at a lower cost compared to the national average.

Open direct carotid artery access for coiling of an intracranial aneurysm under conscious sedation.

We describe the case of a 61-year-old patient with significant medical co-morbidities and tortuous vascular anatomy presenting with a large middle cerebral artery aneurysm. To avoid the risks of general anesthesia and circumvent a majority of the tortuous vessels, the aneurysm was accessed by direct open exposure of the common carotid artery under conscious sedation and local anesthesia. We were able to achieve complete endovascular occlusion of the aneurysm and the patient tolerated the procedure well with no intra- or post-operative complications. Use of conscious sedation is possible and safe for direct open common carotid artery access in patients with significant vascular tortuosity that makes the standard trans-femoral approach difficult or impossible.

Beware of the aneurysm in stealth mode!

Endovascular treatment is one of the treatment options considered for acute stroke in many primary stroke centers. Outcome from such treatment can be very successful and gratifying if the intervention is timely and patient selection is appropriate. There are however certain pitfalls that need to be kept in mind which, if the interventionalist is not careful, can adversely affect the outcome. We describe such a case where the patient presented with acute stroke due to basilar artery thrombosis but also had an aneurysm in the affected vessel. We also make certain recommendations to reduce the chances of complications arising during treatment of patients with such a condition.

Time-dependent changes in cerebrospinal fluid metal ions following aneurysm subarachnoid hemorrhage and their association with cerebral vasospasm.

Aneurysm subarachnoid hemorrhage affects 10 in 100,000 people annually, 40 % of whom will develop neurological deficits from ischemic stroke caused by cerebral vasospasm. Currently, the underlying mechanisms are uncertain. Metal ions are important modulators of neuronal electrophysiological conduction and smooth muscle cell activity, thereby potentially contributing to vasospasm. We hypothesized that metal ion concentrations in the cerebrospinal fluid (CSF) after aneurysm rupture would change over time and be associated with vasospasm. To test this hypothesis, for 21 days, we collected CSF from patients with aneurysmal rupture and subjected it to spectrometry to detect metals. A repeated measures analysis was performed to analyze concentration changes over time. Six of the seven patients with aneurysmal rupture experienced vasospasm, all resolving by day 14. Changes in Fe²âº and Zn²âº concentrations in the CSF paralleled the incidence of vasospasm in this study population. Na²âº, Ca²âº, Mg²âº, and Cu²âº concentrations exhibited no statistically significant changes over time. In conclusion, Fe²âº concentration in the CSF was significantly elevated during days 7-10, whereas Zn²âº concentrations spiked shortly thereafter, during days 11-14. This suggests that Fe²âº may be related to the induction of vasospasm and Zn²âº may be a marker of early brain injury secondary to ischemic injury and inflammation.

The penumbra coil 400 system for treatment of wide-necked intracranial aneurysms: initial single-center experience.

Endovascular treatment of wide-necked intracranial aneurysms frequently requires stent- or balloon-assisted coiling to prevent coil herniation into the parent artery. Provided that coils can be securely deployed within the aneurysm sac, these adjunctive devices and their associated risk can be avoided. The Penumbra 400 Coil (PC-400) has a larger diameter than conventional coils and is constructed completely of metal, a feature that increases the coil stability and may improve its ability to respect the aneurysm neck. The purpose of this study was to examine the frequency of adjunctive stent usage when coiling wide-necked intracranial aneurysms with the PC-400 in comparison with conventional coils. We examined consecutive patients with unruptured wide-necked aneurysms treated at our institution with endovascular coils. Aneurysm characteristics and procedural outcomes were compared between patients treated with PC-400 compared with a control group treated with conventional coils. Thirty-eight patients met criteria for this study. Stent-assisted coiling was required in 34 % fewer cases using PC-400 compared with conventional coils (P = .049). Fewer coils and less length were required with the PC-400 to obtain the same packing densities, occlusion types, and short-term stability. This may reduce treatment cost and prove to be valuable in patients with contraindications to dual antiplatelet therapy.

Optimum timing of revascularization for emergent admissions of carotid artery stenosis with infarction.

OBJECTIVE: There is debate concerning the optimum timing of revascularization for emergent admissions of carotid artery stenosis with infarction. Our intent was to stratify clinical and economic outcomes based on the timing of revascularization. METHODS: We performed a retrospective cohort study using the Nationwide Inpatient Sample from 2002 to 2011. Patients were included if they were admitted non-electively with a primary diagnosis of carotid artery stenosis with infarction and subsequently treated with revascularization. Cases were stratified into four groups based upon the timing of revascularization: (1) within 48-h of admission, (2) between 48-h and day four of hospitalization, (3) between days five and seven, and (4) during the second week of admission. RESULTS: 27,839 cases met our inclusion criteria. The lowest odds of iatrogenic complications (OR=0.643, P<.001) and mortality (OR=0.631, P<.001) coincided with revascularization between days five and seven of hospitalization. Treatment with carotid artery stenting (CAS) and administration of recombinant tissue plasminogen activator (rtPA) increased the odds of complications and death. With regards to economic measures, administration of rtPA and utilization of CAS drove cost and length-of-stay up, while lower co-morbidity burden and earlier time to revascularization drove both measures down. CONCLUSIONS: The present study suggests that the optimum timing of revascularization may be near the end of the first week of hospitalization following acute stroke. However, this study must be cautioned with limitations including its inability to control for critical disease specific variables including symptom severity and degree of stenosis. Prospective examination seems warranted.

Stenting versus endarterectomy and the impact of ultra-early revascularization for emergent admissions of carotid artery stenosis.

BACKGROUND: The factors influencing outcomes after emergent admission for symptomatic carotid artery stenosis treated with revascularization by endarterectomy or stenting are yet to be fully elucidated. METHODS: We analyzed revascularization of carotid artery stenosis for patients admitted emergently using the Nationwide Inpatient Sample (2008-2011). Admission characteristics, economic measures, in-hospital mortality, and iatrogenic stroke were compared between (1) endarterectomy and stenting, (2) patients with and without cerebral infarction, and (3) ultra-early (within 48 hours of admission) and deferred (up to 2 weeks) intervention. RESULTS: 72,797 admissions meeting our inclusion criteria were identified. Factors associated with ultra-early revascularization were male patients, low comorbidity burden, stenosis without infarction, and stenting. Ultra-early intervention significantly decreased cost and length of stay, and stenting for patients without infarction decreased length of stay but increased cost. Patients without infarction treated within 48 hours had significantly lower mortality and iatrogenic stroke rate. Patients with infarction receiving ultra-early revascularization had increased odds of mortality and iatrogenic stroke in comparison with the deferred group. Patients with infarction receiving stenting experienced increased odds of mortality in comparison with those receiving endarterectomy, but there was no significant difference in iatrogenic stroke rate. Recombinant tissue plasminogen activator (rtPA) administration on the day of revascularization greatly increased the odds of iatrogenic stroke and mortality. CONCLUSIONS: Larger prospectively randomized trials evaluating the optimum timing of revascularization after emergent admission of carotid artery stenosis seem warranted.

Early experience with stent retrievers and comparison with previous-generation mechanical thrombectomy devices for acute ischemic stroke.

UNLABELLED: OBJECT.: There is limited information regarding patient outcomes following interventions for stroke during the window for endovascular therapy. Studies have suggested that recently approved stent retrievers are safer and more effective than earlier-generation thrombectomy devices. The authors compared cases in which the Solitaire-FR device was used to those in which a MERCI or Penumbra device was used. METHODS: This study is a single-center retrospective review of 102 consecutive cases of acute stroke in which patients were treated with mechanical thrombectomy devices between 2007 and 2013. Multivariate models, adjusted for confounding factors, were used to investigate functional independence (modified Rankin Scale [mRS] score ≤ 2, and successful reperfusion (thrombolysis in cerebral infarction [TICI] score ≥ 2b). RESULTS: Thrombectomy device had a significant impact on functional independence (mRS score ≤ 2) at discharge from the hospital (p = 0.040). Solitaire-FR treatment resulted in significantly more patients being discharged as functionally independent in comparison with MERCI treatment (p = 0.016). A multivariate model found the use of Solitaire-FR to improve the odds of good clinical outcome in comparison with prior-generation devices (OR 6.283, 95% CI 1.785-22.119, p = 0.004). Additionally, the use of Solitaire-FR significantly increased the odds of successful reperfusion (OR 3.247, 95% CI 1.160-9.090, p = 0.025). CONCLUSIONS: The stent retriever Solitaire-FR significantly improved the odds of functional independence and successful revascularization of the arterial tree. New interventional technology for stroke continues to mature, but randomized trials are needed to establish the actual benefit to specific patient populations.

Acute ischaemic stroke outcomes following mechanical thrombectomy in the elderly versus their younger counterpart: a retrospective cohort study.

OBJECTIVES: Many physicians debate the efficacy of mechanical thrombectomy for ischaemic stroke, but most agree that to establish potential benefit, patient selection must be examined further. People >80 years are a growing population of patients with ischaemic stroke but are largely excluded from clinical trials. The benefit of thrombectomy for them may be greatly reduced due to diminishing neuroplasticity and a larger number of medical comorbidities. To address this knowledge gap, we examined clinical and economic outcomes after mechanical thrombectomy in the ischaemic stroke population from the Nationwide Inpatient Sample. Our null hypotheses were that elderly patients (>80 years) would have a similar rate of inpatient mortality in comparison to their younger counterparts and incur a similar economic expense. DESIGN: Retrospective cohort study. SETTING: A 20% stratified sample of US community hospitals within the Nationwide Inpatient Sample. PARTICIPANTS: All patients from 2008 to 2010 with a primary diagnosis of ischaemic stroke that received mechanical thrombectomy were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was inpatient mortality. Secondary outcomes included hospital charges and length of stay. RESULTS: Less than 1% of all ischaemic stroke cases (9300) were treated with mechanical thrombectomy. Of these, 18% involved patients over 80 years of age. The odds of inpatient mortality in elderly patients treated with mechanical thrombectomy were approximately twice that of their younger counterparts (OR1.993, p < 0.001). The elderly experienced no significant difference in hospital charges (p=0.105) and length of stay (p=0.498). CONCLUSIONS: The odds of inpatient mortality after mechanical thrombectomy in patients over 80 years of age were twice that of their younger counterparts. This is consistent with the overall worse prognosis seen in the natural history of this age group. Studies to better identify patients that would benefit from endovascular mechanical thrombectomy may improve outcomes and reduce the gap currently observed in age stratifications.

Electroretinography during embolization of an ophthalmic arteriovenous fistula.

BACKGROUND: Intraoperative neuromonitoring (IONM) is used for real-time evaluation of neuronal tracts and reflexes in the anesthetized patient, when a neurologic exam is not possible. Changes in IONM signals forewarn of possible neurological deficit. This real-time feedback allows for immediate alterations in therapeutic technique by the treating physician. Transcranial visual evoked potentials are not reliable for evaluating the integrity of the prechiasmatic visual system. Electroretinography (ERG) has been used in animal models for monitoring retinal ischemia and can be used in humans as well to monitor for prechiasmatic ischemia of the retinae and optic nerves. CASE DESCRIPTION: We present a case where ERG signal amplitude and latency changed during ophthalmic arteriovenous fistula embolization, resulting in an intraprocedural decision to refrain from embolization of additional arterial pedicles to preserve vision. After awakening from general anesthesia, the patient had no deficits in visual acuity or field testing, but did complain of transient pain with eye movement that resolved the next day and worsened with episodes of blood pressure elevation. CONCLUSIONS: ERG may be helpful for detecting prechiasmatic ischemic changes during endovascular procedures and may provide early warning signs to the surgeon before the onset of permanent retinal damage. Further investigation is needed to assess the utility of ERG monitoring during the treatment of orbital and periorbital vascular lesions.

Enterprise stent for waffle-cone stent-assisted coil embolization of large wide-necked arterial bifurcation aneurysms.

BACKGROUND: Large wide-necked arterial bifurcation aneurysms present a unique challenge for endovascular coil embolization treatment. One technique described in the literature deploys a Neuroform stent into the neck of the aneurysm in the shape of a waffle-cone, thereby acting as a scaffold for the coil mass. This case series presents four patients with large wide-necked bifurcation aneurysms treated with the closed-cell Enterprise stent using the waffle-cone technique. CASE DESCRIPTION: Four patients (59 ± 18 years of age) with large wide-necked arterial bifurcation aneurysms (three basilar apex and one MCA bifurcation) were treated with the waffle-cone technique using the Enterprise stent as a supporting device for stent-assisted coil embolization. Three of the patients presented with aneurysmal subarachnoid hemorrhage (Hunt-Hess 2-3; Fisher Grade 3-4). There was no procedural morbidity or mortality associated with treatment itself. One aneurysm was completely obliterated, and three had small residual necks. One patient developed an area of PCA infarct and visual field cut one month after the procedure and required recoiling of the residual neck. The flared ends of the Enterprise stent remodeled the aneurysm neck by conforming to the shape of the neck without any technical difficulty, resulting in a stable scaffold holding the coils into the aneurysm. CONCLUSION: The closed cell construction, flexibility, and flared ends of the Enterprise stent allow it to conform to the waffle-cone configuration and provide a stable scaffold for coil embolization of large wide-necked arterial bifurcation aneurysms. We have had excellent initial results using the Enterprise stent with the waffle-cone technique. However, this technique is higher risk than standard treatment methods and therefore should be reserved for large wide-necked bifurcation aneurysms where Y stenting is needed, but not possible, and surgical clip ligation is not an option.

Chronic traumatic encephalopathy.

Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research.

Tandem middle cerebral artery-internal carotid artery occlusions: reduced occlusion-to-revascularization time using a trans-anterior communicating artery approach with a penumbra device.

Rapid revascularization of tandem extracranial and intracranial acute thromboembolic occlusions can be challenging and can delay restoration of blood flow to the cerebral circulation. Taking advantage of collateral pathways in the circle of Willis for thrombectomy can reduce the occlusion-to-revascularization time significantly, thereby protecting brain tissue from ischemic injury. The authors report using the trans-anterior communicating artery (ACoA) approach by using the Penumbra microcatheter to rapidly restore blood flow to the middle cerebral artery (MCA) territory prior to treating the ipsilateral internal carotid artery (ICA) occlusion. Two patients with acute onset of tandem ipsilateral ICA and MCA occlusions and a competent ACoA underwent rapid revascularization of the MCA using a trans-ACoA approach for pharmaceutical and mechanical thrombolysis with the 0.026-in Penumbra microcatheter. Subsequently, once blood flow was reestablished in the MCA territory via cross-filling from the contralateral ICA, the proximally occluded ICA dissection was revascularized with a stent. Both patients had rapid revascularization of the MCA territory (both Thrombolysis in Myocardial Infarction Grade 3) with the trans-ACoA approach (19 and 36 minutes) followed by treatment of the ipsilateral proximal ICA occlusion. This prevented prolonged MCA ischemia time (72 and 47 minutes for ICA revascularization time saved) that would have otherwise occurred if the dissections were treated prior to revascularization of the MCA. Both patients had improved NIH Stroke Scale scores after the procedure. No adverse events from crossing the ACoA with the Penumbra microcatheter were encountered during the revascularization procedure. The trans-ACoA approach with the Penumbra microcatheter for rapid revascularization of an acutely thrombosed MCA in the setting of a simultaneous ipsilateral proximal ICA occlusion is feasible in patients with a competent ACoA. This technique can significantly minimize ischemic injury by reducing the occlusion-to-revascularization time and allow for MCA perfusion via collateral circulation while treating a proximal occlusion. To the best of the authors' knowledge, this is the first reported trans-ACoA approach with the Penumbra microcatheter and the first to report the utilization of the collateral intracranial circulation to reduce occlusion-to-revascularization time.

Bay846, a new irreversible small molecule inhibitor of EGFR and Her2, is highly effective against malignant brain tumor models.

The epidermal growth factor receptor (EGFR) pathway is aberrantly activated in tumors and plays a key role in promoting tumor growth. Small molecule inhibitors which bind reversibly to EGFR have demonstrated limited clinical activity. Thus, there is a continued need to develop novel EGFR inhibitors with improved anti-tumor activity. Bay846 is a newly developed small molecule inhibitor that binds irreversibly to the tyrosine kinase domains of EGFR and Her2. The in vitro and in vivo efficacy of Bay846 was tested using a panel of nine human malignant brain tumor (glioma) models. Lapatinib, a reversible inhibitor of EGFR and Her2, was included for comparison. Six glioma cell lines were sensitive to Bay846 treatment. Bay846 strongly suppressed tumor cell growth in vitro by inducing cell lysis/death rather than cell cycle arrest. Consistent with this, Bay846 had potent anti-tumor activity which led to regressions in tumor size. The active, phosphorylated form of EGFR was reduced by Bay846 treatment in vitro and in tumors. Importantly, the efficacy of Bay846 was significantly greater than lapatinib in all assays. Bay846-sensitivity was associated with expression of a wild-type PTEN in conjunction with high levels of an oncogenic EGFR variant (A289V or EGFRvIII). These studies demonstrate that targeting the EGFR pathway with the irreversible inhibitor Bay846 has great potential to increase the efficacy of this cancer therapy.

Frequency and management of recurrent stenosis after carotid artery stent implantation.

OBJECT: To determine the rate of hemodynamically significant recurrent carotid artery (CA) stenosis after stent-assisted angioplasty for CA occlusive disease, the authors analyzed Doppler ultrasonography data that had been prospectively collected between October 1998 and September 2002 for CA stent trials. METHODS: Patients included in the study participated in at least 6 months of follow-up review with serial Doppler studies or were found to have elevated in-stent velocities (> 300 cm/second) on postprocedure Doppler ultrasonograms. Hemodynamically significant (> or = 80%) recurrent stenosis was identified using the following Doppler criteria: peak in-stent systolic velocity at least 330 cm/second, peak in-stent diastolic velocity at least 130 cm/second, and peak internal carotid artery/common carotid artery velocity ratio at least 3.8. Follow-up studies were obtained at approximate fixed intervals of 1 day, 1 month, 6 months, and yearly. Angiography was performed in the event of recurrent symptoms, evidence of hemodynamically significant stenosis on Doppler ultrasonography, or both. Treatment was repeated because of symptoms, angiographic evidence of severe (> or = 80%) recurrent stenosis, or both of these. Stents were implanted in 142 vessels in 138 patients (all but five patients were considered high-risk surgical candidates and 25 patients were lost to follow-up review). For the remaining 112 patients (117 vessels), the mean duration of Doppler ultrasonography follow up was 16.42+/-10.58 months (range 4-54 months). Using one or more Doppler criteria, severe (> or = 80%) in-stent stenosis was detected in six patients (5%). Eight patients underwent repeated angiography. Six patients (three with symptoms) required repeated intervention (in four patients angioplasty alone; in one patient conventional angioplasty plus Cutting Balloon angioplasty; and in one patient stent-assisted angioplasty). CONCLUSIONS: In a subset of primarily high-risk surgical candidates treated with stent-assisted angioplasty, the rates of hemodynamically significant restenosis were comparable to surgical restenosis rates cited in previously published works. Treatment for recurrent stenosis incurred no instance of periprocedure neurological morbidity.