Investigation and modulation of interleukin-6 following subarachnoid hemorrhage: targeting inflammatory activation for cerebral vasospasm.

BACKGROUND: Cerebral vasospasm (CV) can contribute to significant morbidity in subarachnoid hemorrhage (SAH) patients. A key unknown is how CV induction is triggered following SAH. METHODS: Human aneurysmal blood and cerebral spinal fluid were collected for evaluation. To confirm mechanism, c57/bl6 wild type and c57/bl6 IL-6 female knockout (KO) mice were utilized with groups: saline injected, SAH, SAH + IL-6 blockade, SAH IL-6 KO, SAH IL-6 KO + IL-6 administration, SAH + p-STAT3 inhibition. Dual-labeled microglia/myeloid mice were used to show myeloid diapedesis. For SAH, 50 µm blood was collected from tail puncture and administered into basal cisterns. IL-6 blockade was given at various time points. Various markers of neuroinflammation were measured with western blot and immunohistochemistry. Cerebral blood flow was also measured. Vasospasm was measured via cardiac injection of India ink/gelatin. Turning test and Garcia's modified SAH score were utilized. P < 0.05 was considered significant. RESULTS: IL-6 expression peaked 3 days following SAH (p < 0.05). Human IL-6 was increased in aneurysmal blood (p < 0.05) and in cerebral spinal fluid (p < 0.01). Receptor upregulation was periventricular and perivascular. Microglia activation following SAH resulted in increased caveolin 3 and myeloid diapedesis. A significant increase in BBB markers endothelin 1 and occludin was noted following SAH, but reduced with IL-6 blockade (p < 0.01). CV occurred 5 days post-SAH, but was absent in IL-6 KO mice and mitigated with IL-6 blockade (p < 0.05). IL-6 blockade, and IL-6 KO mitigated effects of SAH on cerebral blood flow (p < 0.05). SAH mice had impaired performance on turn test and poor modified Garcia scores compared to saline and IL-6 blockade. A distinct microglia phenotype was noted day 5 in the SAH group (overlap coefficients r = 0.96 and r = 0.94) for Arg1 and iNOS, which was altered by IL-6 blockade. Day 7, a significant increase in toll-like receptor 4 and Stat3 was noted. This was mitigated by IL-6 blockade and IL-6 KO, which also reduced Caspase 3 (p < 0.05). To confirm the mechanism, we developed a p-STAT3 inhibitor that targets the IL-6 pathway and this reduced NFΚB, TLR4, and nitrotyrosine (p < 0.001). Ventricular dilation and increased Tunel positivity was noted day 9, but resolved by IL-6 blockade (p < 0.05). CONCLUSION: Correlation between IL-6 and CV has been well documented. We show that a mechanistic connection exists via the p-STAT3 pathway, and IL-6 blockade provides benefit in reducing CV and its consequences mediated by myeloid cell origin diapedesis.

Predictors of aneurysm occlusion following treatment with the WEB device: systematic review and case series.

The Woven EndoBridge (WEB) device is becoming increasingly popular for treatment of wide-neck aneurysms. As experience with this device grows, it is important to identify factors associated with occlusion following WEB treatment to guide decision making and screen patients at high risk for recurrence. The aim of this study was to identify factors associated with adequate aneurysm occlusion following WEB device treatment in the neurosurgical literature and in our case series. A systematic review of the present literature was conducted to identify studies related to the prediction of WEB device occlusion. In addition, a retrospective review of our institutional data for patients treated with the WEB device was performed. Demographics, aneurysm characteristics, procedural variables, and 6-month follow-up angiographic outcomes were recorded. Seven articles totaling 450 patients with 456 aneurysms fit our criteria. Factors in the literature associated with inadequate occlusion included larger size, increased neck width, partial intrasaccular thrombosis, irregular shape, and tobacco use. Our retrospective review identified 43 patients with 45 aneurysms. A total of 91.1% of our patients achieved adequate occlusion at a mean follow-up time of 7.32 months. Increasing degree of contrast stasis after WEB placement on the post-deployment angiogram was significantly associated with adequate occlusion on follow-up angiogram (p = 0.005) and with Raymond-Roy classification (p = 0.048), but not with retreatment (p = 0.617). In our systematic review and case series totaling 450 patients with 456 aneurysms, contrast stasis on post-deployment angiogram was identified as a predictor of adequate aneurysm occlusion, while morphological characteristics such as larger size and wide neck negatively impact occlusion.

Adropin decreases endothelial monolayer permeability after cell-free hemoglobin exposure and reduces MCP-1-induced macrophage transmigration.

BACKGROUND: Cell-free heme-containing proteins mediate endothelial injury in a variety of disease states including subarachnoid hemorrhage and sepsis by increasing endothelial permeability. Inflammatory cells are also attracted to sites of vascular injury by monocyte chemotactic protein 1 (MCP-1) and other chemokines. We have identified a novel peptide hormone, adropin, that protects against hemoglobin-induced endothelial permeability and MCP-1-induced macrophage migration. METHODS: Human microvascular endothelial cells were exposed to cell-free hemoglobin (CFH) with and without adropin treatment before measuring monolayer permeability using a FITC-dextran tracer assay. mRNA and culture media were collected for molecular studies. We also assessed the effect of adropin on macrophage movement across the endothelial monolayer using an MCP-1-induced migration assay. RESULTS: CFH exposure decreases adropin expression and increases paracellular permeability of human endothelial cells. Treating cells with synthetic adropin protects against the increased permeability observed during the natural injury progression. Cell viability was similar in all groups and Hmox1 expression was not affected by adropin treatment. MCP-1 potently induced macrophage migration across the endothelial monolayer and adropin treatment effectively reduced this phenomenon. CONCLUSIONS: Endothelial injury is a hallmark of many disease states. Our results suggest that adropin treatment could be a valuable strategy in preventing heme-mediated endothelial injury and macrophage infiltration. Further investigation of adropin therapy in animal models and human tissue specimens is needed.

Low diagnostic yield in follow-up MR imaging in patients with spontaneous intracerebral hemorrhage with a negative initial MRI.

PURPOSE: Follow-up MRI/MRA is historically obtained as outpatient when patients with a spontaneous intracerebral hemorrhage (ICH) have an initial MRI/MRA that is negative for an underlying structural lesion. However, the utility of repeating MR imaging in a delayed fashion remains uncertain. METHODS: We retrospectively reviewed 396 patients with spontaneous ICH admitted at our institution between 2015 and 2017 and selected those whose initial MRI/MRA was negative for an underlying structural lesion and those who underwent follow-up MR imaging in a delayed fashion. RESULTS: A total of 113 patients met the study criteria. The average age of those with negative follow-up MRI/MRA was 65.0 ± 12.6 (IQR: 55.0-74.0) years old. None of the 113 patients with a negative inpatient MRI/MRA had an underlying structural lesion on follow-up MRI/MRA (0%, 95% CI 0.0-0.032, p < 0.001). The mean time of the follow-up imaging from the initial study was 105.7 days (median: 62 days; IQR: 42.5-100.5). Of the 113, 83 (73.5%) underwent follow-up MRI with and without gadolinium, while 30 (26.5%) patients did not receive gadolinium. CONCLUSION: Delayed follow-up MRI in patients with a negative initial MRI/MRA for workup of spontaneous ICH was not diagnostic in any of the patients included in the study. Our study suggests that a routine follow-up MRI for this patient population is not necessary.

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1ß, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs. CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies.

Off-label uses of the Pipeline embolization device: a review of the literature.

The Pipeline embolization device (PED) is the most widely used flow diverter in endovascular neurosurgery. In 2011, the device received FDA approval for the treatment of large and giant aneurysms in the internal carotid artery extending from the petrous to the superior hypophyseal segments. However, as popularity of the device grew and neurosurgeons gained more experience, its use has extended to several other indications. Some of these off-label uses include previously treated aneurysms, acutely ruptured aneurysms, small aneurysms, distal circulation aneurysms, posterior circulation aneurysms, fusiform aneurysms, dissecting aneurysms, pseudoaneurysms, and even carotid-cavernous fistulas. The authors present a literature review of the safety and efficacy of the PED in these off-label uses.

Risk of Venous Thromboembolism in Patients with Large Hemispheric Infarction Undergoing Decompressive Hemicraniectomy.

BACKGROUND: Deep-venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of morbidity and mortality in patients with acute ischemic stroke. This study is the first to examine the risk of venous thromboembolism in patients with large hemispheric infarction undergoing decompressive hemicraniectomy. METHODS: The study population included 95 consecutive patients with a large hemispheric infarction who underwent decompressive hemicraniectomy between 2006 and 2014 at our institution. All patients received prophylactic unfractionated heparin and intermittent compression devices (SCD). Patients were systematically screened for DVT at 5-day interval using Duplex ultrasound. PE was diagnosed on chest CT angiography. RESULTS: Mean age was 57 ± 12 years; mean BMI was 28.3 ± 7.4 kg/m(2). 30.5 % of patients had infarction in the dominant hemisphere and 69.5 % in the non-dominant hemisphere. The mean NIHSS score was 16.0 ± 5 at admission. The mean length of stay was 22 ± 17 days. 35 % of patients developed a DVT including 27 % who developed above-knee DVT and required placement of an inferior vena cava filter. In multivariable analysis, predictors of DVT were an NIHSS ≥ 17 (p = 0.007), seizures (p = 0.003), hypertension (p = 0.03), and increasing length of stay (p = 0.01). The proportion of patients who developed PE was 13 %. In multivariate analysis, BMI ≥ 30 predicted PE (p = 0.05). CONCLUSIONS: The rate of DVT and PE is remarkably high in patients with large hemispheric infarction undergoing decompressive hemicraniectomy despite prophylactic measures. We recommend routine screening for DVT in this population. Interventions beyond the standard prophylactic measures may be necessary in this high-risk group.

Long-Term Pain Reduction Does Not Imply Improved Functional Outcome in Patients Treated With Combined Supraorbital and Occipital Nerve Stimulation for Chronic Migraine.

BACKGROUND: Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied. OBJECTIVE: To present functional outcome studies of combined SONS and ONS for chronic migraine using verified metrics. METHOD: Consecutive patients with both SONS and ONS assessed with Migraine Disability Assessment (MIDAS) and Beck Depression Index (BDI) both preoperatively and postoperatively were studied. Selected predictor variables included patients with ≥50% improvement of pain, disability status, number of years from diagnosis to implantation, and narcotic use. Functional outcome variables included net improvement of ranked MIDAS and BDI scores. Multivariate analysis of variance was performed to assess the correlation between the outcome and predictor variables. RESULTS: Sixteen patients (12 female; average age 52 years old) were studied. Follow-up ranged from 5 to 80 months (average 44.5; σ = 21.4 months). At most recent follow-up, eight patients had a positive response (≥50% improvement in headache), which was the only predictor of functional outcome (total MIDAS, MIDAS-B, and BDI) (p = 0.021). Of note, improvement in functional outcome was only significant during the perioperative 3-6 months period and not throughout long-term follow-up. Among the predictor variables, a strong inverse correlation was found between disability status and positive response to stimulation (r = -0.582). CONCLUSION: There is a paucity of studies in quality of life, productivity, and psychosocial aspects with peripheral nerve stimulation therapy for headache. Patients with a positive response to SONS and ONS also reported overall improvement in their functional status as reflected by MIDAS and BDI in the perioperative period. Unfortunately, this effect waned over the long-term follow-up.

Potential role of aspirin in the prevention of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Inflammation is a key element behind the pathophysiology of cerebral aneurysm formation and rupture. Aspirin is a potent inhibitor of cyclooxygenase-2 (COX), which plays a critical role in the expression of immune modulators known to contribute to cerebral aneurysm formation and rupture. Currently, there are no pharmacological therapies for patients with cerebral aneurysms. Both endovascular and microsurgical interventions may be associated with significant morbidity and mortality. Potentially, a medical alternative that prevents aneurysm progression and rupture may be a beneficial therapy for a significant number of patients. SUMMARY: In animal models, treatment with aspirin and genetic inactivation of COX-2 decreases aneurysm formation and rupture. Selective inhibition of COX-1 did not decrease aneurysm rupture, suggesting that selection inhibition of COX-2 may be critical in thwarting aneurysm progression. Walls of ruptured human intracranial aneurysms have higher levels of COX-2 and microsomal prostaglandin E2 synthase 1 (mPGES-1), both of which are known to be inhibited by aspirin. In a pilot study, patients undergoing microsurgical clipping had attenuated expression of COX-2, mPGES-1, and macrophages in aneurysm walls after 3 months of aspirin therapy versus those that did not receive aspirin. Additionally, in patients undergoing endovascular therapy, local circulating expression of chemokines and COX-2 were increased in blood samples taken from within aneurysm domes as compared to peripheral blood sample controls. Treatment with aspirin also resulted in decreased expression of COX-2 within leukocytes within aneurysms as compared to peripheral blood samples. Novel molecular imaging with ferumoxytol-enhanced MRI may help in the identification of patients at increased risk for aneurysm rupture and assessment of a response to aspirin therapy. Key Messages: Aspirin has been found to be a safe in patients harboring cerebral aneurysms and clinical studies provide evidence that it may decrease the overall rate of rupture. Furthermore, aspirin is an accessible and inexpensive medicine for patients who may not have access to endovascular or microsurgical treatment or for patients who are deemed low risk of aneurysm rupture, high risk for intervention, or both. Future clinical trials are indicated to determine the overall effect of aspirin on aneurysm progression and rupture. This review provides an update on the potential mechanisms and benefits of aspirin in the treatment of cerebral aneurysms.

Unruptured Cerebral Aneurysms: Evaluation and Management.

The evolution of imaging techniques and their increased use in clinical practice have led to a higher detection rate of unruptured intracranial aneurysms. The diagnosis of an unruptured intracranial aneurysm is a source of significant stress to the patient because of the concerns for aneurysmal rupture, which is associated with substantial rates of morbidity and mortality. Therefore, it is important that decisions regarding optimum management are made based on the comparison of the risk of aneurysmal rupture with the risk associated with intervention. This review provides a comprehensive overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management options for unruptured intracranial aneurysms based on the current evidence in the literature. Furthermore, the authors discuss the genetic abnormalities associated with intracranial aneurysm and current guidelines for screening in patients with a family history of intracranial aneurysms. Since there is significant controversy in the optimum management of small unruptured intracranial aneurysms, we provided a systematic approach to their management based on patient and aneurysm characteristics as well as the risks and benefits of intervention.

Management of cerebral cavernous malformations: from diagnosis to treatment.

Cerebral cavernous malformations are the most common vascular malformations and can be found in many locations in the brain. If left untreated, cavernomas may lead to intracerebral hemorrhage, seizures, focal neurological deficits, or headaches. As they are angiographically occult, their diagnosis relies on various MR imaging techniques, which detect different characteristics of the lesions as well as aiding in planning the surgical treatment. The clinical presentation and the location of the lesion are the most important factors involved in determining the optimal course of treatment of cavernomas. We concisely review the literature and discuss the advantages and limitations of each of the three available methods of treatment--microsurgical resection, stereotactic radiosurgery, and conservative management--depending on the lesion characteristics.

Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) may result in a chronic debilitating disease. Dural venous sinus stenosis with a physiologic venous pressure gradient has been identified as a potential etiology in a number of IIH patients. Intracranial venous stenting has emerged as a potential treatment alternative. METHODS: A systematic review was carried out to identify studies employing venous stenting for IIH. RESULTS: From 2002 to 2014, 17 studies comprising 185 patients who underwent 221 stenting procedures were reported. Mean prestent pressure gradient was 20.1 mmHg (95% CI 19.4-20.7 mmHg) with a mean poststent gradient of 4.4 mmHg (95% CI 3.5-5.2 mmHg). Complications occurred in 10 patients (5.4%; 95% CI 4.7-5.4%) but were major in only 3 (1.6%). At a mean clinical follow-up of 22 months, clinical improvement was noted in 130 of 166 patients with headaches (78.3%; 95% CI 75.8-80.8%), 84 of 89 patients with papilledema (94.4%; 95% CI 92.1-96.6%), and 64 of 74 patients with visual symptoms (86.5%; 95% CI 83.0-89.9%). In-stent stenosis was noted in six patients (3.4%; 95% CI 2.5-4.3%) and stent-adjacent stenosis occurred in 19 patients (11.4%; 95% CI 10.4-12.4), resulting in restenting in 10 patients. CONCLUSION: In IIH patients with venous sinus stenosis and a physiologic pressure gradient, venous stenting appears to be a safe and effective therapeutic option. Further studies are necessary to determine the long-term outcomes and the optimal management of medically refractory IIH.

Extending the indications of flow diversion to small, unruptured, saccular aneurysms of the anterior circulation.

BACKGROUND AND PURPOSE: Flow diverters are currently indicated for treatment of large and complex intracranial aneurysms. The purpose of this study was to determine whether the indications of flow diversion can be safely extended to unruptured, small, saccular aneurysms (<10 mm) of the anterior circulation. METHODS: Forty patients treated with the pipeline embolization device (PED) were matched in a 1:4 fashion with 160 patients treated with stent-assisted coiling based on patient age, sex, aneurysm location, and aneurysm size. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared. RESULTS: The rate of periprocedural complications was 5% in the PED group and 3% in the stent-coil group (P=0.7). In multivariable analysis, increasing age was the only predictor of complications. At follow-up, a higher proportion of aneurysms treated with PED (80%) achieved complete obliteration compared with stent-coiled aneurysms (70%) but the difference did not reach statistical significance (P=0.2). In multivariable analysis, increasing aneurysm size and aneurysm location were predictors of nonocclusion. The rate of favorable outcome (modified Rankin Scale, 0-2 and modified Rankin Scale, 0-1) was similar in the PED group and the coil group. CONCLUSIONS: The PED was associated with similar periprocedural risks, clinical outcomes, and angiographic results compared with stent-assisted coiling. These findings suggest that the indications of PED can be safely extended to small intracranial aneurysms that are amenable to conventional endovascular techniques. Larger studies with long-term follow-up are necessary to determine the optimal treatment that leads to the highest rate of obliteration and best clinical outcomes.

Flow diversion versus conventional treatment for carotid cavernous aneurysms.

BACKGROUND AND PURPOSE: Several endovascular treatment options are available for cavernous carotid aneurysms. We compared pipeline embolization device (PED) versus conventional endovascular treatment in terms of evolution of mass effect, complications, recurrence, and retreatment rate. METHODS: One hundred fifty-seven patients harboring 167 cavernous carotid aneurysms were treated using PED placement, coiling, stent-assisted coiling, and carotid vessel destruction. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared. RESULTS: There were no difference in age, sex, and mean aneurysm size between those treated with PED and those treated with conventional endovascular procedures. The patients treated with PED had a significantly lower proportion of small-size aneurysms (<10 mm) and a shorter follow-up duration. Multivariate analysis revealed treatment other than PED (PED: odds ratio [OR], 0.03; P=0.002) and size >15 mm (OR, 4.27; P=0.003) to be predictors of no improvement in symptoms. The rate of complete occlusion was 81.36% (48 of 59) for PED, 42.25% (39 of 71) for stent-assisted coiling, 27.27% (6 of 22) for coiling, and 73.33% (11 of 15) for carotid vessel destruction. Retreatment was needed in patients with aneurysm size >15 mm (OR, 2.67; P=0.037) and those who were not treated with PED (PED: OR, 0.16; P=0.006). The rate of major complications was 6.6% (11 of 167). Patients who were treated with PED or stent-assisted coiling had 3.84 lower odds to develop complications (OR, 0.26; P<0.05). CONCLUSIONS: The use of PED should be encouraged, especially in symptomatic patients. We found PED to be associated with less need for future treatment, higher improvement in symptoms rate, and lower rate of complications.

Critical role of TNF-α in cerebral aneurysm formation and progression to rupture.

BACKGROUND: Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established. METHODS: Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6'dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining. RESULTS: TNF-α knockout mice and those pre-treated with DTH had significantly decreased incidence of aneurysm formation and rupture as compared to sham mice. As compared with sham mice, TNF-α protein and mRNA expression was not significantly different in TNF-α knockout mice or those pre-treated with DTH, but was elevated in unruptured and furthermore in ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days following aneurysm induction. To ensure aneurysm formation preceded rupture, additional mice underwent induction and sacrifice after 7 days. Seventy-five percent had aneurysm formation without evidence of SAH. Initiation of DTH treatment 6 days after aneurysm induction did not alter the incidence of aneurysm formation, but resulted in aneurysmal stabilization and a significant decrease in rupture. CONCLUSIONS: These data suggest a critical role of TNF-α in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-α could be beneficial in preventing aneurysmal progression and rupture.

Flow diversion for complex middle cerebral artery aneurysms.

INTRODUCTION: This study aims to evaluate the safety and efficacy of flow diversion for treatment of large and complex middle cerebral artery (MCA) aneurysms. METHODS: We conducted a retrospective review of the clinical charts of all patients who underwent Pipeline Embolization Device (PED) placement for aneurysm at our institution from October 2010 to October 2013. We included ten patients, of which five had large MCA aneurysms and three had giant ones. Fusiform unruptured aneurysms represented seven of all ten aneurysms. Angiographic and clinical follow-up were available for all patients mostly between 7 and 12 months. RESULTS: We had no technical complications, one periprocedural morbidity, and no mortality. On follow-up, we had no hemorrhagic complications, no aneurysms rupture, and only one clinically significant thromboembolic event in a patient who discontinued antiplatelet therapy against medical advice. One patient had completely occluded his diseased vessel but remained asymptomatic. The overall complication rate is 3/10. On follow-up, complete occlusion occurred in seven patients (7/9). CONCLUSION: PED treatment for large, giant, and bifurcation MCA aneurysms was feasible, with satisfying complete occlusion rate, no mortality, and reasonable morbidity rate.

Staged-volume radiosurgery for large arteriovenous malformations: a review.

Stereotactic radiosurgery is an effective management strategy for properly selected patients with arteriovenous malformations (AVMs). However, the risk of postradiosurgical radiation-related injury is higher in patients with large AVMs. Multistaged volumetric management of large AVMs was undertaken to limit the radiation exposure to the surrounding normal brain. This strategy offers a promising method for obtaining high AVM obliteration rates with minimal normal tissue damage. The use of embolization as an adjunctive method in the treatment of large AVMs remains controversial. Unfortunately, staged-volume radiosurgery (SVR) has a number of potential pitfalls that affect the outcome. The aim of this article is to highlight the role of SVR in the treatment of large AVMs, to discuss the outcome comparing it to other treatment modalities, and to discuss the potential improvement that could be introduced to this method of treatment.

Microsurgery for cerebral arteriovenous malformations: postoperative outcomes and predictors of complications in 264 cases.

OBJECT: The authors conducted a study to assess the safety and efficacy of microsurgical resection of arteriovenous malformations (AVMs) and determine predictors of complications. METHODS: A total of 264 patients with cerebral AVMs were treated with microsurgical resection between 1994 and 2010 at the Jefferson Hospital for Neuroscience. A review of patient data was performed, including initial hemorrhage, clinical presentation, Spetzler-Martin (SM) grade, treatment modalities, clinical outcomes, and obliteration rates. Univariate and multivariate analyses were used to determine predictors of operative complications. RESULTS: Of the 264 patients treated with microsurgery, 120 (45%) patients initially presented with hemorrhage. There were 27 SM Grade I lesions (10.2%), 101 Grade II lesions (38.3%), 96 Grade III lesions (36.4%), 31 Grade IV lesions (11.7%), and 9 Grade V lesions (3.4%). Among these patients, 102 (38.6%) had undergone prior endovascular embolization. In all patients, resection resulted in complete obliteration of the AVM. Complications occurred in 19 (7.2%) patients and resulted in permanent neurological deficits in 5 (1.9%). In multivariate analysis, predictors of complications were increasing AVM size (OR 3.2, 95% CI 1.5-6.6; p = 0.001), increasing number of embolizations (OR 1.6, 95% CI 1.1-2.2; p = 0.01), and unruptured AVMs (OR 2.7, 95% CI 1-7.2; p = 0.05). CONCLUSIONS: Microsurgical resection of AVMs is highly efficient and can be undertaken with low rates of morbidity at high-volume neurovascular centers. Unruptured and larger AVMs were associated with higher complication rates.

Endovascular treatment of a spinal dural arteriovenous malformation (DAVF).

We present a case of a patient with rapid loss of motor strength in his lower extremities. He became bedridden with bowel and bladder incontinence, and developed saddle anesthesia. MRI of the lumbar spine showed edema in the conus medullaris and multiple flow voids within the spinal canal. A spinal angiogram showed a dorsal Type I spinal AVF. This was treated successfully with Onyx 18 (eV3, Irvine, CA). The patient showed rapid post-procedure improvement, and at discharge from the hospital to a rehabilitation center he was fully ambulatory. At 3-year follow-up, the patient was found to ambulate without difficulty. He also had improved saddle anesthesia, and he was voiding spontaneously. There was no evidence of flow voids on repeat MRI of the lumbar spine. The video can be found here: http://youtu.be/SDYNIGNQIW8 .

An algorithmic strategy for selecting a surgical approach in cervical deformity correction.

Adult degenerative cervical kyphosis is a debilitating disease that often requires complex surgical management. Young spine surgeons, residents, and fellows are often confused as to which surgical approach to choose due to lack of experience, absence of a systematic method of surgical management, and today's plethora of information regarding surgical techniques. Although surgeons may be able to perform anterior, posterior, or combined (360°) approaches to the cervical spine, many struggle to rationally choose an appropriate approach for deformity correction. The authors introduce an algorithm based on morphology and pathology of adult cervical kyphosis to help the surgeon select the appropriate approach when performing cervical deformity surgery. Cervical deformities are categorized into 5 different prevalent morphological types encountered in clinical settings. A surgical approach tailored to each category/type of deformity is then discussed, with a concrete case illustration provided for each. Preoperative assessment of kyphosis, determination of the goal for surgery, and the complications associated with cervical deformity correction are also summarized. This article's goal is to assist with understanding the big picture for surgical management in cervical spinal deformity.