Super-selective Wada test for pre-surgical leg motor function assessment: A case report.

INTRODUCTION: Wada test is well-known to assess lateralization of memory and language functions; however, super-selective Wada (ss-Wada) to evaluate motor leg function is rare. We present a ss-Wada test within the anterior cerebral artery (ACA) to assess the motor function of the leg. METHODS: Retrospective chart review. RESULTS: Comprehensive phase-I/II surgical evaluation revealed an ictal focus around the left post-central gyrus with immediate involvement around the left para-central regions. To avoid potential right leg motor dysfunction with the surgery, the patient underwent a ss-Wada procedure. Angiography revealed bilateral ACAs were supplied by the left A1 segment. Super-selective microcatheter injection of amobarbital into the left ACA was performed to avoid cross-filling the contralateral ACA. The ss-Wada test confirmed no right leg motor impairment. Afterward, a craniotomy with direct cortical stimulation confirmed that the left-sided ictal/peri-ictal zone had no clear leg motor function. The patient underwent disconnection of that region and remained seizure-free at 10-month post-op follow-up without any motor or sensory deficits in the right limbs. CONCLUSION: This case demonstrates the proof of concept for ss-Wada in assessing lower extremity motor function. The ss-Wada procedure accurately predicted no motor deficits in the right leg, consistent with preserved motor function post-surgery.

Impact of Balloon Guide Catheter Use on Clinical and Angiographic Outcomes in the STRATIS Stroke Thrombectomy Registry.

Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Intrathecal treatment of cerebral vasospasm.

Treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a major therapeutic challenge. Systemic drug administration is the current treatment of choice, but patients often do not respond beneficially to this approach. Intrathecal (IT) drug administration has several anatomic and pharmacodynamic advantages over conventional systemic treatment of cerebral vasospasm. We reviewed the most recent literature describing IT administration of several drugs to treat aneurysm-induced SAH and cerebral vasospasm, including 16 clinical trials using IT fibrinolytic agents and 10 trials using several IT vasodilators. We evaluated the safety and effectiveness of these trials but made no attempt to perform a meta-analysis using these data. IT drug administration of fibrinolytic agents and vasodilators caused lysis of the subarachnoid clot burden and diminished cerebral vasospasm, respectively. The studies reviewed reported a wide range of drug doses, intervals between aneurysm hemorrhage and initiation of treatment, success of clot dissolution, and degree of vasodilation of vessels in vasospasm. Treatment of vasospasm by IT drug administration is safe and largely effective after the aneurysm has been secured. Our findings indicate that IT treatment effectively delivers a higher drug concentration to vessels in vasospasm with minimal systemic effects. Drugs administered by this route are reported to lyse subarachnoid clots, attenuate cerebral vasospasm, improve clinical outcomes, and decrease the incidence of hydrocephalus. With greater understanding of drug pharmacodynamics, the IT route of drug administration may provide a rational, alternative approach to treating aneurysm-induced cerebral vasospasm.

Single low-dose targeted bevacizumab infusion in adult patients with steroid-refractory radiation necrosis of the brain: a phase II open-label prospective clinical trial.

OBJECTIVE: There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN. METHODS: Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. Images were analyzed by a board-certified neuroradiologist blinded to pretrial diagnosis and treatment status. Secondary outcomes included changes in headache, steroid use, and functional status and absence of neurocognitive sequelae. Comparisons were analyzed using the Fisher exact test, Mann-Whitney U-test, linear mixed models, Wilcoxon signed-rank test, and repeated-measures 1-way ANOVA. RESULTS: Ten adults (mean ± SD [range] age 35 ± 15 [22-62] years) participated in this study. No patients died or exhibited serious adverse effects of systemic bevacizumab. At 3 months, 80% (95% CI 44%-98%) and 90% (95% CI 56%-100%) of patients demonstrated > 25% decrease in RN and vasogenic edema volume, respectively. At 12 months, RN volume decreased by 74% (median [range] 76% [53%-96%], p = 0.012), edema volume decreased by 50% (median [range] 70% [-11% to 83%], p = 0.086), and headache decreased by 84% (median [range] 92% [58%-100%], p = 0.022) among the 8 patients without RN recurrence. Only 1 (10%) patient was steroid dependent at the end of the trial. Scores on 12 of 16 (75%) neurocognitive indices increased, thereby supporting a pattern of cerebral white matter recovery. Two (20%) patients exhibited RN recurrence that required further treatment at 10 and 11 months, respectively, after bevacizumab infusion. CONCLUSIONS: For the first time, to the authors' knowledge, the authors demonstrated that a single low-dose targeted bevacizumab infusion resulted in durable clinical and imaging improvements in 80% of patients at 12 months after treatment without adverse events attributed to bevacizumab alone. These findings highlight that targeted bevacizumab may be an efficient one-time treatment for adults with brain RN. Further confirmation with a randomized controlled trial is needed to compare the intra-arterial approach with the conventional multicycle intravenous regimen. Clinical trial registration no.: NCT02819479 (ClinicalTrials.gov).

The Hydrogel Endovascular Aneurysm Treatment Trial (HEAT): A Randomized Controlled Trial of the Second-Generation Hydrogel Coil.

BACKGROUND: Aneurysm recurrence after coiling has been associated with aneurysm growth, (re)hemorrhage, and a greater need for follow-up. The second-generation HydroCoil Embolic System (HES; MicroVention, Inc) consists of a platinum core with integrated hydrogel and was developed to reduce recurrence through enhancing packing density and healing within the aneurysm. OBJECTIVE: To compare recurrence between the second-generation HES and bare platinum coil (BPC) in the new-generation Hydrogel Endovascular Aneurysm Treatment Trial (HEAT). METHODS: HEAT is a randomized, controlled trial that enrolled subjects with ruptured or unruptured 3- to 14-mm intracranial aneurysms amenable to coiling. The primary endpoint was aneurysm recurrence using the Raymond-Roy scale. Secondary endpoints included minor and major recurrence, packing density, adverse events related to the procedure and/or device, mortality, initial complete occlusion, aneurysm retreatment, hemorrhage from target aneurysm during follow-up, aneurysm occlusion stability, and clinical outcome at final follow-up. RESULTS: A total of 600 patients were randomized (HES, n = 297 and BPC, n = 303), including 28% with ruptured aneurysms. Recurrence occurred in 11 (4.4%) subjects in the HES arm and 44 (15.4%) subjects in the BPC arm (P = .002). While the initial occlusion rate was higher with BPC, the packing density and both major and minor recurrence rates were in favor of HES. Secondary endpoints including adverse events, retreatment, hemorrhage, mortality, and clinical outcome did not differ between arms. CONCLUSION: Coiling of small-to-medium aneurysms with second-generation HES resulted in less recurrence when compared to BPC, without increased harm. These data further support the use of the second-generation HES for the embolization of intracranial aneurysms.

Management of anterior inferior cerebellar artery aneurysms: an illustrative case and review of literature.

Aneurysms of the anterior inferior cerebellar artery (AICA) are relatively rare among intracranial aneurysms. They can occur in 1 of 3 regions of the AICA: 1) craniocaudal (high or low riding), 2) mediolateral-premeatal (proximal), and 3) meatal-postmeatal (distal). The management strategies for treatment differ according to the location and configuration of the aneurysm. The existing body of neurosurgical literature contains articles published on aneurysms arising from the AICA near the basilar artery (BA), intracanalicular/meatal aneurysms, and distal AICA. Several therapeutic options exist, encompassing microsurgical and endovascular techniques. The authors describe a case of treatment involving a large BA-AICA aneurysm approached via exposure of the presigmoid dura using a retromastoid suboccipital craniectomy and partial petrosectomy. Treatment of these lesions requires detailed knowledge of the anatomy, and an anatomical overview of the AICA with its arterial loops and significant branches is presented, including a discussion of the internal auditory (labyrinthine) artery, recurrent perforating arteries, subarcuate artery, and cerebellosubarcuate artery. The authors discuss the various surgical approaches (retromastoid, far lateral, subtemporal, and transclival) with appropriate illustrations, citing the advantages and disadvantages in accessing these AICA lesions in relation to these approaches. The complications of these different surgical techniques and possible clinical effects of parent artery occlusion during AICA surgery are highlighted.

Pipeline Embolization Device for Treatment of Craniocervical Internal Carotid Artery Dissections: Report of 3 Cases.

BACKGROUND: Dissecting pseudoaneurysms of the craniocervical circulation are uncommon, accounting for only 3% of all cerebral aneurysms. These aneurysms pose a challenge due to their location and anatomic configuration. The Pipeline Embolization Device (PED) is a flow diversion technique that successfully treats aneurysms by diverting blood flow away from the aneurysm and reconstructing the diseased parent artery by altering its hemodynamics. CASE DESCRIPTION: We report 3 cases in which the PED was used to treat craniocervical carotid artery dissection with associated pseudoaneurysms. A single PED was used in the first case, 4 PEDs were used in the second case, and 3 PEDs and a PRECISE PRO RX carotid stent were placed in the third case. All 3 patients achieved full neurologic recovery postoperatively. Cerebral angiography performed postoperatively demonstrated revascularization, good laminar flow, and no in-stent or adjacent stenosis. CONCLUSIONS: PED placement offers a safe and effective method of treating spontaneous or traumatic craniocervical carotid artery dissections with excellent neurologic outcomes postoperatively and complete long-term aneurysmal occlusion.

Endovascular Treatment for Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: An Observational Study of Clinical Indications, Surgical Technique, and Long-Term Outcomes.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure. IIH causes significant morbidity marked by incapacitating headaches and visual disturbances. This study investigated the long-term outcomes of venous sinus stenting in a large group of patients with IIH. METHODS: We retrospectively reviewed all patients at our institution who underwent venous sinus stenting for IIH over 6 years (July 1, 2012-June 30, 2018). A particular focus was dedicated to collecting demographic, clinical, radiologic, and outcomes data. All patients had failed medical management. RESULTS: Of the 110 patients evaluated for IIH, 42 underwent venous sinus stenting, with a mean follow-up of 25.6 months (range, 8.7-60.7 months). The mean age was 32 years (range, 15-52 years), 38 (90%) were women, and the mean body mass index was 35.6 kg/m2 (range, 18.6-47.5 kg/m2). Prior to the stenting procedure, all patients had headaches, visual disturbances, and papilledema. Of the 39 patients who had an ophthalmologic evaluation poststenting, 29 (74%) had resolution of their papilledema. Eighteen patients (43%) had complete resolution of their headaches after the stenting procedure, whereas 22 patients (52%) remained under a neurologist's care for chronic migraine and other types of headaches. Two patients underwent a restenting procedure for disease progression, and 1 patient experienced an in-stent thrombosis. CONCLUSIONS: A multidisciplinary approach involving neurosurgeons, ophthalmologists, radiologists, and neurologists is integral in the management of patients with IIH to prevent the complications of papilledema. Venous sinus stenting offers a safe and effective means of treating IIH.

Operative intracranial infection following craniotomy.

OBJECT: Postoperative infection after cranial surgery is a serious complication that requires immediate recognition and treatment. In certain cases such as postoperative meningitis, the patient can be treated with antibiotics only. In cases that involve a bone flap infection, subdural empyema, or cerebral abscess, however, reoperation is often needed. There has been significant disagreement regarding the incidence of postoperative central nervous system (CNS) infections following cranial surgery. In this paper the authors' goal was to perform a retrospective review of the incidence of CNS infection after cranial surgery at their institution. They focused their review on those patients who required repeated surgery to treat the infection. METHODS: The authors reviewed the medical records and imaging studies in all patients who underwent a craniotomy or stereotactic drainage for CNS infection over the past 10 years. Subgroup analysis was then performed in patients whose infection was a result of a previous cranial operation to determine the incidence, factors associated with infection, and the type of infectious organism. Patients treated nonoperatively (that is, those who received intravenous antibiotics for postoperative meningitis or cellulitis) were not included. Patients treated for wound infection without intracranial pus were also not included. RESULTS: During the study period from January 1997 through December 2007, approximately 16,540 cranial surgeries were performed by 25 neurosurgeons. These included elective as well as emergency and trauma cases. Of these cases 82 (0.5%) were performed to treat postoperative infection in 50 patients. All 50 patients underwent their original surgery at the authors' institution. The median age was 51 years (range 2-74 years). There were 26 male and 24 female patients. The most common offending organism was methicillin-sensitive Staphylococcus aureus, which was found in 10 of 50 patients. Gram-negative rods were found in 15 patients. Multiple organisms were identified in specimens obtained in 5 patients. Six patients had negative cultures. Most craniotomies leading to subsequent infection were performed for tumors or other mass lesions (23 of 50 patients), followed by craniotomies for hemorrhage and vascular lesions. Almost half of the patients underwent > 1 cranial operation before presenting with infection. CONCLUSIONS: Postoperative infection after cranial surgery is an important phenomenon that needs immediate recognition. Even with strict adherence to sterile techniques and administration of antibiotic prophylaxis, a small percentage of these patients will develop an infection severe enough to require reoperation.

Brain abscess formation at the site of intracerebral hemorrhage secondary to central nervous system vasculitis.

Brain abscess is a rare but very dangerous neurosurgical lesion. Prompt diagnosis and emergency surgical evacuation are the hallmarks of therapy. Brain abscess following ischemic and hemorrhagic stroke is a rare entity. These cases are often preceded by episodes of bacteremia, sepsis, and local infection. The authors report the case of a 30-year-old woman who presented with a cerebral abscess at the site of a recent intraparenchymal hemorrhage.

Molecular genetics of familial cerebral cavernous malformations.

Cerebral cavernous malformations (CMs) are angiographically occult neurovascular lesions that consist of enlarged vascular channels without intervening normal parenchyma. Cavernous malformations can occur as sporadic or autosomal- dominant inherited conditions. Approximately 50% of Hispanic patients with cerebral CMs have the familial form, compared with 10 to 20% of Caucasian patients. There is no difference in the pathological findings or presentation in the sporadic and familial forms. To date, familial CMs have been attributed to mutations at three different loci: CCM1 on 7q21.2, CCM2 on 7p15-p13, or CCM3 on 3q25.2-q27. The authors summarize the current understanding of the molecular events underlying familial CMs.

Aneurysm Study of Pipeline in an Observational Registry (ASPIRe).

BACKGROUND AND OBJECTIVE: Few prospective studies exist evaluating the safety and efficacy of the Pipeline Embolization Device (PED) in the treatment of intracranial aneurysms. The Aneurysm Study of Pipeline In an observational Registry (ASPIRe) study prospectively analyzed rates of complete aneurysm occlusion and neurologic adverse events following PED treatment of intracranial aneurysms. MATERIALS AND METHODS: We performed a multicenter study prospectively evaluating patients with unruptured intracranial aneurysms treated with PED. Primary outcomes included (1) spontaneous rupture of the Pipeline-treated aneurysm; (2) spontaneous nonaneurysmal intracranial hemorrhage (ICH); (3) acute ischemic stroke; (4) parent artery stenosis, and (5) permanent cranial neuropathy. Secondary endpoints were (1) treatment success and (2) morbidity and mortality at the 6-month follow-up. Vascular imaging was evaluated at an independent core laboratory. RESULTS: One hundred and ninety-one patients with 207 treated aneurysms were included in this registry. The mean aneurysm size was 14.5 ± 6.9 mm, and the median imaging follow-up was 7.8 months. Twenty-four aneurysms (11.6%) were small, 162 (78.3%) were large and 21 (10.1%) were giant. The median clinical follow-up time was 6.2 months. The neurological morbidity rate was 6.8% (13/191), and the neurological mortality rate was 1.6% (3/191). The combined neurological morbidity/mortality rate was 6.8% (13/191). The most common adverse events were ischemic stroke (4.7%, 9/191) and spontaneous ICH (3.7%, 7/191). The complete occlusion rate at the last follow-up was 74.8% (77/103). CONCLUSIONS: Our prospective postmarket study confirms that PED treatment of aneurysms in a heterogeneous patient population is safe with low rates of neurological morbidity and mortality. Patients with angiographic follow-up had complete occlusion rates of 75% at 8 months.

Pineal region giant cell astrocytoma associated with tuberous sclerosis: case report.

Tuberous sclerosis complex is a genetic disorder characterized by the development of hamartomas in multiple organs including the brain, skin, eye, kidney, and heart. Neurological features include seizures and mental retardation. Cortical tubers and subependymal nodules are the characteristic intracranial lesions of tuberous sclerosis. Subependymal giant cell astrocytomas, typically located adjacent to the foramen of Monro, can enlarge and cause symptomatic ventricular obstruction. The authors describe the case of a 3-year-old boy with a history of tuberous sclerosis and retinal lesions who presented with an enlarging enhancing pineal region mass. Via an infratentorial supracerebellar approach, the mass was removed using both the operative microscope and a rigid neuroendoscope. Pathological examination showed a giant cell astrocytoma. To the authors' knowledge, this is the first reported case of tuberous sclerosis associated with a giant cell astrocytoma of the pineal region. Diagnostic considerations are discussed.

Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain.

Radiation necrosis (RN) is a serious complication that can occur in up to 10% of brain radiotherapy cases, with the incidence dependent on both dose and brain location. Available medical treatment for RN includes steroids, vitamin E, pentoxifylline, and hyperbaric oxygen. In a significant number of patients, however, RN is medically refractory and the patients experience progressive neurological decline, disabling headaches, and decreased quality of life. Vascular endothelial growth factor (VEGF) is a known mediator of cerebral edema in RN. Recent reports have shown successful treatment of RN with intravenous bevacizumab, a monoclonal antibody for VEGF. Bevacizumab, however, is associated with significant systemic complications including sinus thrombosis, pulmonary embolus, gastrointestinal tract perforation, wound dehiscence, and severe hypertension. Using lower drug doses may decrease systemic exposure and reduce complication rates. By using an intraarterial route for drug administration following blood-brain barrier disruption (BBBD), the authors aim to lower the bevacizumab dose while increasing target delivery. In the present report, the authors present the cases of 2 pediatric patients with cerebral arteriovenous malformations, who presented with medically intractable RN following stereotactic radiosurgery. They received a single intraarterial infusion of 2.5 mg/kg bevacizumab after hyperosmotic BBBD. At mean follow-up duration of 8.5 months, the patients had significant and durable clinical and radiographic response. Both patients experienced resolution of their previously intractable headaches and reversal of cushingoid features as they were successfully weaned off steroids. One of the patients regained significant motor strength. There was an associated greater than 70% reduction in cerebral edema. Intraarterial administration of a single low dose of bevacizumab after BBBD was safe and resulted in durable clinical and radiographic improvements at concentrations well below those required for the typical systemic intravenous route. Advantages over the intravenous route may include higher concentration of drug delivery to the affected brain, decreased systemic toxicity, and a significantly lower cost.

p38 Mitogen-activated protein kinases on the body surface--a function for p38 delta.

The p38 family of mitogen-activated protein kinases includes p38 alpha (SAPK2a, CSBP), p38 beta (SAPK2b), p38 delta (SAPK4), and p38 gamma (SAPK3/ERK6). p38 alpha and p38 beta are widely expressed p38 isoforms that are involved in regulation of cell proliferation, differentiation, development, and response to stress. Relatively less is known regarding the function of the p38 delta isoform. In this review, we discuss the role of the p38 alpha, p38 beta, and p38 gamma isoforms and then present recent findings that define a role for p38 delta as a regulator of differentiation-dependent gene expression in keratinocytes.

Regulation of involucrin gene expression.

The epidermis is a dynamic renewing structure that provides life-sustaining protection from the environment. The major cell type of the epidermis, the epidermal keratinocyte, undergoes a carefully choreographed program of differentiation. Alteration of these events results in a variety of debilitating and life-threatening diseases. Understanding how this process is regulated is an important current goal in biology. In this review, we summarize the literature regarding regulation of involucrin, an important marker gene that serves as a model for understanding the mechanisms that regulate the differentiation process. Current knowledge describing the role of transcription factors and signaling cascades in regulating involucrin gene expression are presented. These studies describe a signaling cascade that includes the novel protein kinase C isoforms, Ras, MEKK1, MEK3, and a p38delta-extracellular signal regulated kinase 1/2 complex. This cascade regulates activator protein one, Sp1, and CCATT/enhancer-binding protein transcription factor DNA binding to two discrete involucrin promoter regions, the distal- and proximal-regulatory regions, to regulate involucrin gene expression.

Mechanical thrombectomy as first-line treatment for venous sinus thrombosis: technical considerations and preliminary results using the AngioJet device.

BACKGROUND: Cerebral venous sinus thrombosis (CVT) is an uncommon cause of stroke that is usually treated medically with intravenous heparin therapy followed by long-term anticoagulation therapy. A series of patients with CVT who underwent rheolytic thrombectomy with the AngioJet as a first-line adjunctive treatment in addition to standard anticoagulation therapy is presented. METHODS: Prospectively maintained endovascular databases at two institutions were retrospectively reviewed. The available clinical and imaging data were compiled at each institution and combined for analysis. RESULTS: Over 18 months, 13 patients (seven women and six men; age range 17-73 years, median age 45 years) with CVT were treated with rheolytic thrombectomy. Immediate (partial or complete) recanalization of the thrombosed intracranial sinuses was achieved in all patients. At a median radiographic follow-up of 7 months there was continued patency of all recanalized sinuses. Clinical follow-up was available on nine patients: modified Rankin score of 0 in four patients, 1 in three patients and 6 in two patients. CONCLUSION: This series demonstrates the feasibility of performing mechanical thrombectomy as a first-line treatment for acute CVT. This technique facilitates the prompt restoration of intracranial venous outflow, which may result in rapid neurological and symptomatic improvement.

Multimodality treatment of a ruptured grade IV posterior fossa arteriovenous malformation in a patient pregnant with twins: case report.

INTRODUCTION: Brain arteriovenous malformations (AVM) account for a significant percentage of brain hemorrhages in pregnant patients. There is general consensus that ruptured AVMs in pregnant women should be managed based on neurosurgical rather than obstetric considerations. Since the risk of re-hemorrhage is significantly higher in the pregnant patient with a ruptured AVM, aggressive treatment during pregnancy must be considered if this can be accomplished with acceptable risk. Recent advances in endovascular technology have increased the potential for successful treatment of previously inoperable high-grade AVMs. CASE REPORT: A 17-year-old woman pregnant with twins experienced sudden onset headache and became unresponsive at 20 weeks gestation. A CT scan of the head showed cerebellar hemorrhage and obstructive hydrocephalus. Cerebral angiography showed a 5.5 cm AVM in the cerebellar vermis with deep drainage for a Spetzler Martin grade IV classification. Extensive two-stage Onyx embolization with complete casting of the nidus was performed. The patient delivered healthy twin girls at 36 weeks gestation by a planned cesarean section. This was followed by surgical resection of the AVM 4 months later with minimal blood loss. A follow-up angiogram showed no evidence of AVM recurrence 3 months after surgical resection. Her balance was significantly improved and she walked unassisted. She had mild cerebellar speech. Her twin girls are progressing normally. CONCLUSION: Extensive endovascular Onyx embolization is feasible in the setting of a ruptured high-grade AVM during pregnancy. The rationale for proceeding with treatment is the perceived higher likelihood of re-hemorrhage from such a lesion.