Inflammatory mediators in vascular disease: identifying promising targets for intracranial aneurysm research.

Inflammatory processes are implicated in many diseases of the vasculature and have been shown to play a key role in the formation of intracranial aneurysms (IAs). Although the specific mechanisms underlying these processes have been thoroughly investigated in related pathologies, such as atherosclerosis, there remains a paucity of information regarding the immunopathology of IA. Cells such as macrophages and lymphocytes and their effector molecules have been suggested to be players in IA, but their specific interactions and the role of other components of the inflammatory response have yet to be determined. Drawing parallels between the pathogenesis of IA and other vascular disorders could provide a roadmap for developing a mechanistic understanding of the immunopathology of IA and uncovering useful targets for therapeutic intervention. Future research should address the presence and function of leukocyte subsets, mechanisms of leukocyte recruitment and activation, and the role of damage-associated molecular patterns in IA.

Diagnosis and treatment of arterial dissections.

Dissections of the cervical and intracranial vessels represent an important source of stroke in those less than 50 years of age. This can occur spontaneously or following trauma, minor or major. Rapid diagnosis is essential to limit subsequent sequelae and modern computed tomographic angiography represents an appropriately sensitive modality. Treatment must be individualized to the patient and can consist of an antiplatelet regimen, anticoagulation, or endovascular intervention. No evidence demonstrates superiority of either medical modality and even aspirin alone may be efficacious. Consideration should be given to this in the multi-trauma population in which more aggressive anticoagulation is contraindicated. In addition, thrombolytic administration should not be withheld would it otherwise be indicated. Endovascular intervention is reserved for those with hemodynamically significant narrowing, enlarging pseudoaneurysms, fistulas formation, or subarachnoid hemorrhage.

Influence of weekend hospital admission on short-term mortality after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There is expanding literature to show that certain patients admitted during the weekend have worse outcomes than similar patients admitted during the week. Although many clinicians have hypothesized the presence of this "weekend effect" with patients with intracerebral hemorrhage, there is a paucity of studies validating this conjecture. METHODS: We performed a retrospective cohort study of patients with intracerebral hemorrhage (International Classification of Diseases, 9th Revision, Clinical Modification=431) extracted from the 2004 Nationwide Inpatient Sample. Multivariable logistic regression analyses and Cox proportional hazards regression were conducted to calculate the odds of death (within 7, 14, and 30 days) and the hazard ratio of death for patients with weekend intracerebral hemorrhage admissions compared with weekday intracerebral hemorrhage admissions. All analyses were adjusted for concurrent differences in length of stay, patient demographics, and comorbid disease. RESULTS: Weekend hospital admissions accounted for 26.8% of the 13 821 patients with a diagnosis of intracerebral hemorrhage in the National Inpatient Sample. Admission during the weekend was a statistically significant independent predictor of death within 7 days (OR, 1.14; 95% CI, 1.05 to 1.25), within 14 days (OR, 1.15; 95% CI, 1.05 to 1.25), and within 30 days (OR, 1.15; 95% CI, 1.05 to 1.25). The adjusted hazard of in-hospital death (hazard ratio, 1.12; CI, 1.05 to 1.20) indicates that the overall risk of in-hospital death with intracerebral hemorrhage is 12% higher with weekend admission. CONCLUSIONS: Weekend admission for intracerebral hemorrhage was associated with increased risk-adjusted mortality when compared with admission during the remainder of the week.

Operative nuances of an occipital artery to posterior inferior cerebellar artery bypass.

Occipital artery to posterior inferior cerebellar artery bypasses remain an important tool for cerebrovascular neurosurgeons, particularly in the management of complex aneurysms of the posterior inferior cerebellar artery requiring proximal occlusion or trapping. The procedure requires meticulous technique and attention to detail. The authors outline their technique for accomplishing this bypass emphasizing nuances for complication avoidance.

Endovascular management of spinal vascular malformations: history and literature review.

Spinal vascular malformations represent a complex group of entities whose treatment paradigm continually evolves. Given the ever-increasing role of endovascular therapy, it is the goal of the authors to review the current literature regarding this therapeutic tool and to provide recommendations guiding management. A thorough literature search was conducted using Medline, with subsequent articles being identified through cross-referencing. The analysis revealed that, since its introduction in the 1960s, endovascular therapy has been used to manage the entire spectrum of spinal vascular malformations, during which period it has undergone considerable technological and technical evolution. As such, embolization has proved of growing therapeutic utility, largely resulting from the mounting evidence supporting its safety and efficacy, in addition to the inherent minimally invasive nature. This alternative to surgical intervention will be increasingly used as first-line therapy in spinal vascular malformations.

Hyperperfusion syndrome following endovascular cerebral revascularization.

Endovascular cerebral revascularization is becoming a frequently used alternative to surgery for the treatment of atherosclerotic disease, especially in the intracranial circulation where options are limited. Recent literature regarding the equivalent efficacy of carotid artery stenting and carotid endarterectomy in certain patient populations, as well as the recognition of the significant risk for recurrent stroke posed by intracranial lesions, will only serve to amplify this trend. Hyperperfusion syndrome has been well documented in the setting of carotid endarterectomy; however, a paucity of literature exists regarding the incidence, pathophysiology, and management as it relates to percutaneous interventions. The purpose of this review is to outline the current state of knowledge, with particular attention to the distinct attributes of endovascular treatment that would be expected to modify the course of hyperperfusion syndrome.

Traumatic high flow vertebral-venous fistula presenting with delayed ischemic stroke: endovascular management with detachable coils and Amplatzer Vascular Plugs.

Penetrating injuries to the neck can result in a number of abnormalities that are of interest to neurosurgeons and interventional neuroradiologists. Gunshot or stab wounds may cause damage to the cervical spinal cord, the adjacent osseous and ligamentous structures, and the peripheral or cranial nerves. In addition, a significant percentage of penetrating wounds to this location result in vascular injury. These may present insidiously or acutely and with a variety of symptoms. The authors present the case of a patient in whom an occipital lobe infarction developed roughly 2 months after the patient was struck in the neck by a bullet. He was found to have a complete transection of the left vertebral artery, with an associated vertebral-venous fistula. The fistula was eventually treated endovascularly with a combination of platinum coils and Amplatzer Vascular Plugs. The management is discussed, with specific emphasis on the technical aspects of the case.

A review of therapeutic strategies for the management of cerebral venous sinus thrombosis.

OBJECT: Although initially described in the 19th century, cerebral venous sinus thrombosis (CVST) remains a diagnostic and therapeutic dilemma. It has an unpredictable course, and the propensity for hemorrhagic infarction produces significant consternation among clinicians when considering anticoagulation. It is the purpose of this review to analyze the evidence available on the management of CVST and to provide appropriate recommendations. METHODS: A thorough literature search was conducted through MEDLINE and PubMed, with additional sources identified through cross-referencing. A classification and level of evidence assignment is provided for recommendations based on the American Heart Association methodologies for guideline composition. RESULTS: Of the publications identified, the majority were isolated case reports or small case series. Few prospective trials have been conducted. Existing data support the use of systemic anticoagulation as an initial therapy in all patients even in the presence of intracranial hemorrhage. Chemical and/or mechanical thrombectomy, in conjunction with systemic anticoagulation, is an alternative strategy in patients with progressive deterioration on heparin therapy or in those who are moribund on presentation. Mechanical thrombectomy is probably preferred in patients with preexisting intracranial hemorrhage. CONCLUSIONS: Effective treatments exist for the management of CVST, and overall outcomes are more favorable than those for arterial stroke. Further research is necessary to determine the role of individual therapies; however, the rarity of the condition poses a significant limitation.

New insights into the causes and therapy of cerebral vasospasm following subarachnoid hemorrhage.

Cerebral vasospasm lingers as the leading preventable cause of death and disability in patients who experience aneurysmal subarachnoid hemorrhage. Despite the potentially devastating consequences of cerebral vasospasm, the mechanisms behind it are incompletely understood. Nitric oxide, endothelin-1, bilirubin oxidation products and inflammation appear to figure prominently in its pathogenesis. Therapies directed at many of these mechanisms are currently under investigation and hold significant promise for an ultimate solution to this substantial problem.

Evolution of cerebral revascularization techniques.

As a leading cause of death and disability in patients across the world, stroke is a problem that plagues both neurosurgeons and neurologists alike. Whether a result of atherosclerosis, moyamoya disease, or a complication in the treatment of a complex intracranial aneurysm, cerebrovascular occlusion can have devastating effects on patients. For nearly half a century neurosurgeons have searched for safer, more effective ways to increase the amount of blood flow to ischemic brain tissue. From the first extracranial-intracranial bypasses to the recent technological advancements seen with endovascular therapy, cerebral revascularization techniques have been constantly evolving. Over the years cerebral ischemia has gone from a condition that was previously considered surgically untreatable, to a condition with several viable options for prevention and treatment. In this paper the authors discuss the historical evolution of treatment for cerebrovascular occlusive disease.

Endovascular Management of Multiple Dysplastic Aneurysms in a Young Man with an Unknown Underlying Cause: A Case Report and Review of the Literature.

BACKGROUND: Intracranial aneurysms are the leading cause of nontraumatic subarachnoid hemorrhage and are most commonly associated with the anterior cerebral artery (ACA) and anterior communicating artery complex. We describe the presentation and management of a 27-year-old man with concurrent bilateral A1-2 junction aneurysms and fusiform intraorbital ophthalmic artery (OA) aneurysms. CASE DESCRIPTION: A 27-year-old man with no past medical history presented with 3 months of headaches. Imaging showed a large dysplastic left A1-2 junction aneurysm and a smaller saccular right A1-2 junction aneurysm, with potentially adherent domes. Two fusiform aneurysms of the intraorbital segment of the left OA were also identified. The patient underwent coil-assisted pipeline embolization of the left A1-A2 aneurysm, with complete obliteration and reconstitution of the normal parent vessel. The patient underwent coil embolization of the right A1-2 aneurysm 3 weeks later, which was found to have grown significantly at the time of treatment. Three-month follow-up showed spontaneous resolution of the OA aneurysms, persistent obliteration of the left aneurysm, and significant recurrence of the right aneurysm, which was treated with stent-assisted coil embolization. A second recurrence 3 months later was successfully treated with repeat coiling. At the time of this treatment, the patient was also found to have 2 de novo distal middle cerebral artery and ACA dysplastic aneurysms, which were not treated. Follow-up angiography 6 weeks later showed stable complete obliteration of the right A1-2 aneurysm and interval complete resolution of the dysplastic middle cerebral artery aneurysm. The distal ACA aneurysm was observed to have minimally increased in size; however, the parent vessel showed signs of interval partial thrombosis with contrast stasis within the aneurysm. This final aneurysm is being followed with serial imaging. The patient remains neurologically intact with complete resolution of his headaches. CONCLUSIONS: We report the case of a young man with no past medical history who presented with multiple dysplastic aneurysms. Successful staged endovascular intervention resulted in obliteration of aneurysms with spontaneous obliteration of the intraorbital OA aneurysms observed at 3 months. We present this case to review the multiple challenges of managing complex ACA aneurysms and to highlight the usefulness of endovascular intervention in their treatment.

Endovascular Management of a Ruptured Basilar Perforator Artery Aneurysm Associated with a Pontine Arteriovenous Malformation: Case Report and Review of the Literature.

BACKGROUND: Arteriovenous malformation (AVM)-associated aneurysms are common, reported in 15% of cases. Regarding the ruptured posterior fossa AVMs, associated aneurysms are present in 48% of cases and are the cause of the bleed in 37%. We present a 75-year-old female who presented with a subarachnoid hemorrhage secondary to a ruptured aneurysm arising from a flow-related basilar perforator artery feeder of an anterior pontine AVM. We report the successful treatment of the aneurysm with coil embolization. CASE DESCRIPTION: A 75-year-old female presented with subarachnoid hemorrhage primarily contained within the posterior fossa. Angiography demonstrated a 2 × 3-mm fusiform aneurysm arising from a basilar perforator feeding pedicle of an anterior 1 × 2-cm pontine AVM. Venous drainage from the AVM was predominantly to the superior petrosal vein. Under roadmap guidance, super-selective catheterization of the basilar perforator aneurysm was performed. Three HydroSoft 3D coils were deployed within the aneurysm, resulting in complete obliteration. The patient was discharged on postbleed day 15 to an inpatient rehabilitation facility. Follow-up angiography at 5 months demonstrated stable complete obliteration. The patient made a complete recovery and was living independently at the time of this report. CONCLUSIONS: Basilar trunk perforator aneurysms are rare lesions, particularly in the setting of brainstem AVMs. We report successful endovascular treatment of a flow-related ruptured basilar perforator aneurysm associated with an anterior pontine AVM. To the best of our knowledge, this is the second report addressing this scenario. We hope that the information presented here serves to guide future surgical decision making and management.

External lumbar drain: A pragmatic test for prediction of shunt outcomes in idiopathic normal pressure hydrocephalus.

BACKGROUND: The consensus on most reliable supplemental test to predict the shunt responsiveness in patients with idiopathic normal pressure hydrocephalus (iNPH) is lacking. The aim of this study is to discuss the utility of external lumbar drain (ELD) in evaluation of shunt responsiveness for iNPH patients. METHODS: A retrospective review of 66 patients with iNPH was conducted. All patients underwent 4-day ELD trial. ELD-positive patients were offered ventriculoperitoneal shunt (VPS) surgery. The primary outcome evaluation parameters were gait and mini mental status examination (MMSE) assessment. The family and patient perception of improvement was accounted for in the outcome evaluation. RESULTS: There were 38 male and 28 female with mean age of 74 years (range 45-88 years). ELD trial was positive in 86% (57/66) of patients. No major complications were encountered with the ELD trial. A total of 60 patients (57 ELD-positive, 3 ELD-negative) underwent VPS insertion. The negative ELD trial (P = 0.006) was associated with poor outcomes following shunt insertion. The positive ELD trial predicted shunt responsiveness in 96% patients (P < 0.0001, OR = 96.2, CI = 11.6-795.3). A receiver operating characteristic (ROC) curve analysis revealed that the ELD trial is reasonably accurate in differentiating shunt responder from non-responder in iNPH patients (area under curve = 0.8 ± 0.14, P = 0.02, CI = 0.52-1.0). The mean follow-up period was 12-months (range 0.3-3 years). The significant overall improvement after VPS was seen in 92% (55/60). The improvement was sustained in 76% of patients at mean 3-year follow-up. The number of comorbid conditions (P = 0.034, OR = 4.15, CI = 1.2-9.04), and a history of cerebrovascular accident (CVA) (P = 0.035, OR = 4.4, CI = 1.9-14.6) were the predictors of poor outcome following shunt surgery. CONCLUSION: The positive ELD test predicted shunt responsiveness in 96% of patients. With adequate technique, maximal results with minimal complications can be anticipated. The number of comorbidities, history of CVA and negative ELD test were significantly associated with poor shunt outcomes.

Intraoperative ultrasound guidance for the placement of permanent ventricular cerebrospinal fluid shunt catheters: a single-center historical cohort study.

OBJECTIVE: Despite the frequency with which ventriculoperitoneal shunts are placed, ventricular catheter revision rates remains as high as 30%-40% at 1 year. Many neurosurgeons place ventricular catheters "blindly" depending on anatomical landmarks and personal experience. To determine whether intraoperative ultrasonography is beneficial for ventricular catheter placement, we performed a historical cohort study comparing shunts placed with intraoperative ultrasound (US) guidance to those placed blindly. METHODS: We reviewed all shunts placed by the Department of Neurosurgery at the University of Virginia from January 2005 to January 2007. During that time 211 patients underwent 242 shunts, with US use determined by surgeon's preference. Ninety-two shunts were placed by the use of US guidance, and 150 were placed without US. Adults received 176 shunts, 56 with US. Children received 66 shunts, 36 with US. Mean follow-up was 21.6 months. The primary end points examined were shunt revision, ventricular catheter revision (VCR), and acute VCR (revision within 1 week for an improperly-placed catheter). RESULTS: The use of US was associated with a statistically significant decrease in shunt revisions (odds ratio 0.492; 95% confidence interval 0.253-0.958). Of the shunts placed with US guidance, 21.7% required revision, compared with 29.3% without US. VCRs and acute VCRs occurred in 9.8% and 2.2%, respectively, for US shunts, compared with 14% and 5.3% without US. Pediatric revision rates were 30.6% with US versus 53.3% without, whereas adult rates were 16.1% and 23.3%, respectively. The benefit of US was more profound for occipital shunts. CONCLUSIONS: The use of US for the placement of permanent cerebrospinal fluid shunt catheters is associated with a decreased risk of shunt revision.

Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV. Estrogen, specifically 17 ß -estradiol (E2), has potential therapeutic implications for ameliorating the delayed neurological deterioration which follows aneurysmal SAH. We review the causes of CV and DCI and examine the evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin-1 production. E2 provides neuroprotection by increasing thioredoxin expression, decreasing c-Jun N-terminal kinase activity, increasing neuroglobin levels, preventing SAH-induced suppression of the Akt signaling pathway, and upregulating the expression of adenosine A2a receptor. The net effect of E2 modulation of these various effectors is the promotion of neuronal survival, inhibition of apoptosis, and decreased oxidative damage and inflammation. E2 is a potentially potent therapeutic tool for improving outcomes related to post-SAH CV and DCI. However, clinical evidence supporting its benefits remains lacking. Given the promising preclinical data available, further studies utilizing E2 for the treatment of patients with ruptured intracranial aneurysms appear warranted.

Multi-institutional neurosurgical training initiative at a tertiary referral center in Mwanza, Tanzania: where we are after 2 years.

BACKGROUND: The paucity of neurosurgical care in East Africa remains largely unaddressed. A sustained investment in local health infrastructures and staff training is needed to create an independent surgical capacity. The Madaktari organization has addressed this issue by starting initiatives to train local general surgeons and assistant medical officers in basic neurosurgical procedures. We report illustrative cases since beginning of the program in Mwanza in 2009 and focus on the most recent training period. METHODS: A multi-institutional neurosurgical training program and a surgical database was created at a tertiary referral center in Mwanza, Tanzania. We collected clinical data on consecutive patients who underwent a neurosurgical procedure between September 9th and December 1st, 2011. All procedures were performed by a local surgeon under the supervision of a visiting neurosurgeon. Since the inception of the training initiative, comprehensive multidisciplinary training courses in Tanzania and an annual visiting fellowship for East African surgeons to travel to a major U.S. medical center have been established. RESULTS: At initial visits infrastructure and feasibility of complex case scenarios was assessed. Surgeries for brain tumors and complex spinal cases were performed. During the 3-month training period, 62 patients underwent surgery. Pediatric hydrocephalus comprised 52% of patients, 11% suffered from meningomyelocelia, and 6% presented with an encephalocele. A total of 24% of patients were treated for trauma-related conditions, representing 75% of the adult patients. A total of 10% of patients had surgery because of traumatic spine injury, and 15% of operations were on patients with severe head injury. A total of 6% of patients presented with degenerative spine disease. One patient sustained a fatal perioperative complication. At the end of the training period, the local general surgeon was able to perform all basic neurosurgical cases independently. CONCLUSIONS: Neurosurgical care in Tanzania needs to address a diverse, unique disease burden. We found that local surgeons could be enabled to safely perform basic cranial and spinal neurosurgical procedures through immersive, 1-on-1 on-site collaborations, multidisciplinary courses, and educational visiting fellowships.

Tumor necrosis factor-α modulates cerebral aneurysm formation and rupture.

Inflammation is a critical process behind cerebral aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in cerebral aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment of macrophages, activation of chemotactic cytokines, upregulation of matrix remodeling genes, production of free radicals leading to oxidative stress, and ultimately cellular apoptosis. Recent studies have indicated that TNF-α may be a potential target for the development of novel medical therapies, but additional experimental data is needed to clarify the intricacies of TNF-α activation and its critical downstream targets in cerebral aneurysms. This review provides an update on the mechanisms underlying TNF-α-induced molecular modulation in cerebral aneurysms.

Vascular smooth muscle cells in cerebral aneurysm pathogenesis.

Vascular smooth muscle cells (SMC) maintain significant plasticity. Following environmental stimulation, SMC can alter their phenotype from one primarily concerned with contraction to a pro-inflammatory and matrix remodeling phenotype. This is a critical process behind peripheral vascular disease and atherosclerosis, a key element of cerebral aneurysm pathology. Evolving evidence demonstrates that SMCs and phenotypic modulation play a significant role in cerebral aneurysm formation and rupture. Pharmacological alteration of smooth muscle cell function and phenotypic modulation could provide a promising medical therapy to inhibit cerebral aneurysm progression. This study reviews vascular SMC function and its contribution to cerebral aneurysm pathophysiology.

Single-center experience with a dual microcatheter technique for the endovascular treatment of wide-necked aneurysms.

OBJECT: The endovascular treatment of wide-necked aneurysms can be technically challenging due to distal coil migration or impingement of the parent vessel. In this paper, the authors illustrate an alternative method for the treatment of wide-necked intracranial aneurysms using a dual microcatheter technique. METHODS: The authors' first 100 consecutive patients who underwent coil embolization of a wide-necked aneurysm using a dual microcatheter technique are reported. With this technique, 2 microcatheters are used to introduce coils into the aneurysm. The coils are deployed either sequentially or concurrently to form a stable construct and prevent coil herniation or migration. Angiographic and clinical outcomes are reported. RESULTS: The technical success rate of the dual microcatheter technique is 91% with a morbidity and mortality of 1% and 2%, respectively. Clinical outcomes are excellent with 93% of patients demonstrating a modified Rankin Scale score of 0-2 at long-term follow-up regardless of their score at presentation. Retreatment rates are 18%. CONCLUSIONS: The dual microcatheter technique may be a safe and efficacious first line of treatment for widenecked aneurysms.

Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.