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Background: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots., Methods: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee., Results: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P <0.001), pointing to a potential preprocedure indicator of challenging clot., Conclusions: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03685578.

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).

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., (© Congress of Neurological Surgeons 2020.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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/m 2 (range, 18.6-47.5 kg/m 2 ). 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., (Copyright © 2018. Published by Elsevier Inc.)

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., (© 2017 The Authors.)

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., (© 2017 American Heart Association, Inc.)

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.

Background and Purpose: Flow diverters are increasingly used in the endovascular treatment of intracranial aneurysms. Our aim was to determine neurologic complication rates following Pipeline Embolization Device placement for intracranial aneurysm treatment in a real-world setting., Materials and Methods: We retrospectively evaluated all patients with intracranial aneurysms treated with the Pipeline Embolization Device between July 2008 and February 2013 in 17 centers worldwide. We defined 4 subgroups: internal carotid artery aneurysms of ≥10 mm, ICA aneurysms of <10 mm, other anterior circulation aneurysms, and posterior circulation aneurysms. Neurologic complications included spontaneous rupture, intracranial hemorrhage, ischemic stroke, permanent cranial neuropathy, and mortality. Comparisons were made with t tests or ANOVAs for continuous variables and the Pearson χ(2) or Fisher exact test for categoric variables., Results: In total, 793 patients with 906 aneurysms were included. The neurologic morbidity and mortality rate was 8.4% (67/793), highest in the posterior circulation group (16.4%, 9/55) and lowest in the ICA <10-mm group (4.8%, 14/294) (P = .01). The spontaneous rupture rate was 0.6% (5/793). The intracranial hemorrhage rate was 2.4% (19/793). Ischemic stroke rates were 4.7% (37/793), highest in patients with posterior circulation aneurysms (7.3%, 4/55) and lowest in the ICA <10-mm group (2.7%, 8/294) (P = .16). Neurologic mortality was 3.8% (30/793), highest in the posterior circulation group (10.9%, 6/55) and lowest in the anterior circulation ICA <10-mm group (1.4%, 4/294) (P < .01)., Conclusions: Aneurysm treatment with the Pipeline Embolization Device is associated with the lowest complication rates when used to treat small ICA aneurysms. Procedure-related morbidity and mortality are higher in the treatment of posterior circulation and giant aneurysms., (© 2015 by American Journal of Neuroradiology.)

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.

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., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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.

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.

Background and Importance: Intracranial venous hypertension is known to be associated with venous outflow obstruction. We discuss the diagnosis and treatment of mechanical venous outflow obstruction causing pseudotumor cerebri., Clinical Presentation: We report 2 patients presenting with central venous outflow obstruction secondary to osseous compression of the internal jugular veins at the craniocervical junction. The point of jugular compression was between the lateral tubercle of C1 and a prominent, posteriorly located styloid process. In both cases, catheter venography showed high-grade jugular stenosis at the level of C1 with an associated pressure gradient. The dominant jugular vein was decompressed after the styloid process was resected. Postoperative imaging confirmed resolution of the jugular stenosis and normalization of preoperative pressure gradients. In both cases, the symptoms of intracranial hypertension resolved., Conclusion: Intracranial venous hypertension may result from extrinsic osseous compression of the jugular veins at the skull base. Although rare, this phenomenon is important to recognize because primary stenting not only is ineffective but also may actually exacerbate the outflow obstruction. The osseous impingement of the dominant jugular vein can be relieved via a decompressive styloidectomy, and the clinical results can be excellent.

Object: Chiropractic manipulation of the cervical spine is a known cause of craniocervical arterial dissections. In this paper, the authors describe the patterns of arterial injury after chiropractic manipulation and their management in the modern endovascular era., Methods: A prospectively maintained endovascular database was reviewed to identify patients presenting with craniocervical arterial dissections after chiropractic manipulation. Factors assessed included time to symptomatic presentation, location of the injured arterial segment, neurological symptoms, endovascular treatment, surgical treatment, clinical outcome, and radiographic follow-up., Results: Thirteen patients (8 women and 5 men, mean age 44 years, range 30-73 years) presented with neurological deficits, head and neck pain, or both, typically within hours or days of chiropractic manipulation. Arterial dissections were identified along the entire course of the vertebral artery, including the origin through the V(4) segment. Three patients had vertebral artery dissections that continued rostrally to involve the basilar artery. Two patients had dissections of the internal carotid artery (ICA): 1 involved the cervical ICA and 1 involved the petrocavernous ICA. Stenting was performed in 5 cases, and thrombolysis of the basilar artery was performed in 1 case. Three patients underwent emergency cerebellar decompression because of impending herniation. Six patients were treated with medication alone, including either anticoagulation or antiplatelet therapy. Clinical follow-up was obtained in all patients (mean 19 months). Three patients had permanent neurological deficits, and 1 died of a massive cerebellar stroke. The remaining 9 patients recovered completely. Of the 12 patients who survived, radiographic follow-up was obtained in all but 1 of the most recently treated patients (mean 12 months). All stents were widely patent at follow-up., Conclusions: Chiropractic manipulation of the cervical spine can produce dissections involving the cervical and cranial segments of the vertebral and carotid arteries. These injuries can be severe, requiring endovascular stenting and cranial surgery. In this patient series, a significant percentage (31%, 4/13) of patients were left permanently disabled or died as a result of their arterial injuries.

Objective: The cause of pseudotumor cerebri, or benign intracranial hypertension (BIH), is controversial. We report our results from 18 cases of venous sinus stenting (VSS), the largest series in the literature, with specific focus on the rate of technical success, amelioration of the subjective symptom of headache, attendant complications, and radiographic patency on follow-up., Methods: Review of our prospectively maintained database identified 18 patients who had undergone 19 VSS procedures for the placement of 30 stents in the past 2.5 years. Indications for treatment included a clinical diagnosis of BIH with venographic demonstration of stenosis., Results: VSS was technically successful in all patients (100%). No patient suffered a permanent complication. Three patients were lost to follow-up. The remaining 15 patients were followed clinically and asked to rate their headache severity on a scale of 1 to 10 both before and after VSS. Overall, 12 patients (80%) qualified their headaches as better after VSS, two stated that they were the same, and one patient said that they were worse. Of 14 patients who underwent follow-up angiography, all demonstrated normal patency of the stented segments. In one of these patients, stenosis was detected on follow-up in the unstented segment of the sigmoid sinus and jugular bulb., Conclusions: VSS is highly effective (80%) in ameliorating headache associated with BIH. The procedure is associated with a high rate of technical success (100%), a low rate of permanent complications (0), and a high rate of stent patency on follow-up angiography (100%)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Traditional endovascular treatment of cranial dural arteriovenous fistulas (DAVFs) consists of a transarterial approach with n-butylcyanoacrylate (nBCA) or a transvenous approach with coil embolization. The advent of Onyx in the endovascular arsenal potentially offers a high probability of obliteration of these vascular lesions through a purely transarterial route., Methods: A retrospective review of the Barrow Neurological Institute endovascular database between October 2005 and November 2009 highlighted 50 patients with 63 cranial DAVFs that were treated with transarterial Onyx, with and without adjuvant embolysates, for a total of 76 embolization procedures. Hospital records, cerebral angiography and other diagnostic imaging and clinical visits were reviewed., Results: At a median follow-up of 5 months (range 0-25 months), complete angiographic cure was obtained in 41 patients with 50 (79%) DAVFs after transarterial embolization using Onyx combined with other embolysates. When Onyx was used as the sole embolic agent, 32 of 37 DAVFs (87%) in 29 (of 33) patients achieved angiographic cure. Subgroup analysis showed that by using the middle meningeal artery (MMA) as a conduit for primary Onyx embolization, angiographic cures were achieved in 27 of the 37 DAVFs (73%). Periprocedural complications occurred in six (7.9%) sessions in one patients (8%). Only one patient had a permanent complication (2%) with unimproved cranial nerve palsies., Conclusion: Transarterial Onyx embolization of cranial DAVFs, particularly using the MMA as a conduit, is a safe and effective curative therapy.

Objective: We present 2 cases of carotid-cavernous fistulas that failed multiple attempts at transarterial and transvenous embolization. Direct transorbital puncture for embolization was successful in curing the fistulas. The relevant anatomy and technique are reviewed., Clinical Presentation: The first case is a 39-year-old man who presented with a 2-month history of worsening right-sided chemosis, proptosis, double vision, and progressive right eye vision loss. The second case is a 79-year-old woman with a 5-month history of right-sided chemosis and a 1-month history of complete left ophthalmoplegia. Cerebral angiography revealed an indirect carotid-cavernous fistula (CCF) in both patients, supplied by meningeal branches of the internal and/or external carotid arteries., Intervention: After multiple unsuccessful attempts at transarterial and transvenous embolization, the CCFs were accessed via direct percutaneous transorbital puncture of the inferior and superior ophthalmic veins, respectively. The fistulas were then successfully occluded with a combination of Onyx and detachable coils., Conclusion: In rare cases in which more conventional transvenous and transarterial routes to a CCF have been exhausted, direct percutaneous transorbital puncture represents a viable means of achieving catheterization of the fistulous connection. In most cases, where a prominent arterialized superior ophthalmic vein is present, direct puncture represents a reasonable alternative to ophthalmologic cut-down procedures. Transorbital puncture of the inferior ophthalmic vein provides a direct route to the cavernous sinus in cases where the superior ophthalmic vein is atretic and inaccessible by direct surgical cut-down procedures.

A patient with a giant partially thrombosed basilar apex aneurysm was treated with balloon-assisted coil embolization. At the conclusion of the embolization, an Enterprise stent was placed from the upper basilar artery to the left P1 segment. Follow-up angiography 4 months later showed that the distal stent had pulled out of the posterior cerebral artery and was in the coil mass within the aneurysm. Angiography clearly showed that the stent had migrated down the basilar artery and that the artery was now kinked proximal to the stent. Nonetheless, the left posterior cerebral artery and the basilar artery were still widely patent. This is the first documented case in which a stent 'compacted' into a completed coiled aneurysm in a delayed fashion.

Objective: This is the largest contemporary series of distal posterior cerebral artery (PCA) aneurysms treated by use of endovascular coiling and stenting as well as surgical clipping, clip wrapping, and bypass techniques. We propose a new treatment paradigm., Methods: The location, size, type of aneurysm, clinical presentation, treatment, complications, and outcomes associated with 34 distal PCA aneurysms in 33 patients (15 females, 18 males; mean age, 44 years) were reviewed retrospectively., Results: The most common presenting symptom was headache in 19 (58%) followed by contralateral weakness or numbness in 6 (18%) and visual changes in 4 (12%). Eight aneurysms were giant. Of the remaining 26 aneurysms, 17 were fusiform/dissecting, 5 were saccular, and 4 were mycotic. Treatment was primarily endovascular in 22 patients, 12 of whom also had a concomitant surgical bypass procedure. Nine patients underwent microsurgical clipping, and 3 underwent combined treatment of clipping and coiling and/or stenting. There were no significant differences in outcomes between the groups (P=.078). The recurrence rate in patients undergoing coiling was 22% and 0% in patients undergoing clipping. Fourteen aneurysms (41%) involved treatment with an occipital artery-to-PCA bypass or an onlay graft. Compared with their preoperative status, these patients had significantly worse outcomes than those without a bypass (P=.013)., Conclusion: Bypass techniques for the treatment of distal PCA aneurysms are associated with a higher rate of complications than once thought. In our new treatment paradigm, bypass is a last resort and reserved for patients in whom balloon-test occlusion fails, who refuse parent-vessel sacrifice, and who cannot undergo primary stenting with coiling or clip wrapping.

Objective: We present our management of a unique case of complex arteriovenous shunt with vascular steal in the left-sided head and neck vessels in a child with CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and deafness) syndrome., Clinical Presentation: A 10-year-old girl presented with high-output heart failure. Cerebral angiography revealed high-flow abnormal fistulous connections between the left common carotid artery and innominate vein as well as between the vertebral artery and innominate vein. There was significant collateral blood flow to the fistulae from the left external carotid artery and left thyrocervical and costocervical trunks., Intervention: The left vertebral artery-to-innominate vein fistula was occluded by endovascular means during temporary balloon occlusion. The left common carotid artery-to-innominate vein fistula was occluded through neck dissection with surgical clipping., Conclusion: Combined neurosurgical and endovascular techniques were used successfully to manage a complex arteriovenous fistula in a patient with CHARGE syndrome. Challenges in therapeutic decision making are discussed.

Background: Vertebral origin angioplasty and stenting (VOAS) with bare metal stents is associated with a high rate of in-stent restenosis (ISR)., Objective: We evaluated the rate of ISR after VOAS with drug-eluting stents., Methods: Twenty patients (15 men, 5 women; age range, 36-88 years; mean, 63.7 years) were treated for VOAS with a paclitaxel-eluting stent (Taxus Express2, Boston Scientific, Natick, Massachusetts). Stenosis at follow-up was quantified as insignificant (0%-24%), mild (25%-49%), moderate (50%-74%), and severe (75%-100%). ISR was defined using a binary criteria of >50% stenosis at follow-up angiography., Results: All procedures were technically successful with no periprocedural complications. Follow-up angiography (range, 4-48 months; mean, 14.7 months) showed insignificant stenosis in 9 patients, mild in 6, moderate in 4, and severe in 1. In 1 patient with "moderate" stenosis, the stent migrated distally; therefore, the lesion restenosis was not within the stent. Thus, 4 of 19 patients (21%) exhibited binary moderate or severe ISR, and 5 of 20 showed restenosis at the lesion (25%). The patient with severe stenosis developed stent thrombosis>3 years after VOAS., Conclusion: VOAS with drug-eluting stents was associated with a low incidence of periprocedural complications. Although the rate of restenosis was half that seen with the use of bare metallic stents, 21% of patients still developed moderate or severe ISR. These patients may require>or=1 revascularization procedures. The risk of delayed stent thrombosis may necessitate lifelong dual antiplatelet medications.

Introduction: Occlusion of the basilar artery (BA) has a poor prognosis. We evaluated technical considerations and complications associated with reopening subacute to chronically occluded BAs., Methods: Duration of BA occlusion before revascularization, symptoms and medical management before treatment, and postprocedural antiplatelet regimen and anticoagulation protocols of 9 patients were analyzed. All patients underwent endovascular low-volume balloon angioplasty followed by Wingspan stenting., Results: The median time between onset of symptoms and treatment was 5 days (range, 2 days to 3.5 years). The median time between documentation of BA occlusion by cerebral angiography or computed tomography angiography and treatment was 3 days (range, 1 day to 8 months). Recanalization was successful in 8 of the 9 patients. Immediately after the procedure, 4 patients were stable, 3 patients improved, and 2 patients were worse. Four patients had periprocedural complications. Four of the 9 patients died, 2 from periprocedural complications. The mean clinical duration of follow-up was 11 months. At latest follow-up, the modified Rankin Scale scores for the 5 surviving patients were 0, 0, 2, 2, and 3, respectively. During the follow-up period, 4 patients improved, 1 patient remained stable, and 1 patient died. The mean angiographic follow-up was 8.6 months. Two patients developed significant in-stent stenosis during this period., Conclusion: With current endovascular techniques, recanalization of chronically occluded BAs is feasible. The procedure carries substantial risks and should be reserved for patients with medically refractory symptoms. Careful postprocedural medical management and radiographic follow-up are warranted to prevent in-stent restenosis.

Objective: An endovascular approach is often the first-line treatment of dural arteriovenous fistulae (DAVFs). Information on the use of Onyx (ev3 Neurovascular, Irvine, CA) for treating DAVFs, however, is limited. Therefore, we present our early experience, technical considerations, and complications associated with the use of Onyx for DAVF embolization., Methods: Twenty-eight patients with 29 DAVFs treated with Onyx embolization were included in this analysis. Hospital records, operative reports, and angiograms were reviewed and analyzed., Results: Forty Onyx procedures, including 39 transarterial and 1 transvenous approaches, were performed. Fifty-one external carotid artery branches, 8 posterior meningeal artery branches, and 3 internal carotid artery branches were used for Onyx embolization. Branches of the middle meningeal artery were embolized 32 times, and the occipital artery was embolized 15 times. Twenty-one fistulae (72%) were cured angiographically with endovascular therapy. Transarterial embolization via the middle meningeal artery cured 12 DAVFs (41%). Four complications (9.7%) were recorded, including 3 transient (7.3%) and 1 permanent neurological deficits (2.4%). Follow-up imaging, which was available for 8 fistulae with angiographic cures, showed no evidence of recurrence., Conclusion: Transarterial Onyx embolization of external carotid artery branches, particularly the middle meningeal artery, offers a high likelihood of cure. This technique provides a safe and effective method of embolization with few side effects and complications. However, long-term follow-up is needed to establish its efficacy.

Surgical resection is the treatment of choice for most intracranial meningiomas. We review the current state of adjuvant therapies, including radiation and chemotherapy. Conventional external beam radiation and stereotactic radiosurgery remain second-line options for patients unwilling or unable to undergo surgery. Radiation therapy is most useful in the setting of recurrent or residual tumor after surgical resection, where it is associated with a clear increase in the length of progression-free survival. This survival advantage is most pronounced with high-grade meningiomas, which have a much higher recurrence rate than low-grade meningiomas, even after gross total resection. In contrast, the role of chemotherapy in the treatment of meningiomas is limited. This treatment modality is often reserved for inoperable tumors or those refractory to radiation treatment. Furthermore, the choice of chemotherapy agents is limited. Hydroxyurea, a ribonucleotide reductase inhibitor, has modest clinical activity in meningiomas. In recent small clinical trials, somatostatin analogues have been moderately effective in controlling tumor growth.

Cavernous malformations (CMs) or hemangiomas arising from within the dural sinuses are rare entities that differ from their parenchymal counterparts in that they are highly vascular lesions. While parenchymal CMs are typically angiographically occult, intrasinus malformations may have large, dural-based arterial feeding vessels that are amenable to preoperative embolization. The novel liquid embolic Onyx (ev3, Inc.) is an ideal agent for the embolization of these lesions. The authors present the first known case of a giant intrasinus CM embolized with Onyx before gross-total resection. The authors report the case of a 9-year-old boy with brief apneic episodes in whom MR imaging revealed a giant CM arising from within the right transverse and sigmoid sinuses and infiltrating the right tentorium cerebelli. At another institution, the patient had undergone 1 prior embolization and 2 unsuccessful attempts at resection. Both surgeries had been complicated by massive blood loss and were aborted. Under the authors' care, the patient underwent preoperative transarterial embolization with Onyx during which a substantial volume of the mass lesion was filled with embolisate. Subsequently, complete circumferential excision of the mass from the tentorium was accomplished with minimal intraoperative blood loss.

Object: Tapping of a suspected malfunctioning ventriculoperitoneal shunt is usually easy, sometimes informative, but also potentially misleading. The purpose of this study was to determine the effectiveness of a shunt evaluation protocol that does not involve direct shunt tapping except in rare and specific cases., Methods: The authors adopted a protocol for shunt evaluation that involves shunt tapping only in selected cases of suspected infection or in patients with noncommunicating hydrocephalus and equivocal computed tomography (CT) findings of shunt infection. They then reviewed the clinical characteristics and surgical findings in 373 consecutive assessments of 155 pediatric patients who were evaluated for shunt malfunction and/or infection by using this protocol between January 2003 and December 2005., Results: Mental status change and headache were the symptoms most concordant with shunt malfunction, but no symptom had a predictive value much better than 50%. Follow-up CT scans demonstrated enlarged ventricles in 72 of 126 cases of shunt revision. Among those with obstruction but without remarkable CT changes, 8 patients had evidence of distal obstruction on x-ray "shunt series" consisting of skull, chest, and abdominal radiographs, and 5 had obvious symptoms that rendered further testing unnecessary; 38 cases of obstruction were diagnosed based on elevated opening pressure on lumbar puncture (mean 34.7 cm H(2)O). A shunt tap was required in only 8 cases (2%)., Conclusions: The authors have shown that it is possible to evaluate the majority of ventricular shunt malfunctions without tapping the device. Because it is possible to diagnose shunt obstruction correctly by other means, the shunt tap may not be obligatory as a routine test of the device's patency.

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 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.

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.

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.

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.

Tazarotene-induced protein 3 (TIG3) is a recently discovered regulatory protein that is expressed in the suprabasal epidermis. In the present study, we show that TIG3 regulates keratinocyte viability and proliferation. TIG3-dependent reduction in keratinocyte viability is accompanied by a substantial increase in the number of sub-G1 cells, nuclear shrinkage, and increased formation of cornified envelope-like structures. TIG3 localizes to the membrane fraction, and TIG3-dependent differentiation is associated with increased type I transglutaminase activity. Microscopic localization and isopeptide cross-linking studies suggest that TIG3 and type I transglutaminase co-localize in membranes. Markers of apoptosis, including caspases and poly(ADP-ribose) polymerase, are not activated by TIG3, and caspase inhibitors do not stop the TIG3-dependent reduction in cell viability. Truncation of the carboxyl-terminal membrane-anchoring domain results in a complete loss of TIG3 activity. The morphology of the TIG3-positive cells and the effects on cornified envelope formation suggest that TIG3 is an activator of terminal keratinocyte differentiation. Our studies suggest that TIG3 facilitates the terminal stages in keratinocyte differentiation via activation of type I transglutaminase.

The epidermis is a dynamic and continually renewing surface that provides and maintains a life-sustaining interface with the environment. The epidermal keratinocyte, the major cell type of the epidermis, undergoes a complex and carefully choreographed program of differentiation. This process requires a balance between keratinocyte proliferation, differentiation, and apoptosis. This overview will concentrate on cascades that regulate the balance between keratinocyte cell proliferation and survival, and apoptosis and cell differentiation, with a particular emphasis on the role of the mitogen-activated protein kinase cascades. A summary of the literature suggests that extracellular regulated kinases function to promote keratinocyte proliferation and survival, whereas p38 mitogen-activated protein kinase functions to promote differentiation and apoptosis.

A signaling cascade that includes protein kinase C (PKC), Ras, and MEKK1 regulates involucrin (hINV) gene expression in epidermal keratinocytes (Efimova, T., LaCelle, P., Welter, J. F., and Eckert, R. L. (1998) J. Biol. Chem. 273, 24387-24395 and Efimova, T., and Eckert, R. L. (2000) J. Biol. Chem. 275, 1601-1607). Because signal transfer downstream of MEKK1 may involve several MAPK kinases (MEKs), it is important to evaluate the regulatory role of each MEK isoform. In the present study we evaluate the role of MEK6 in transmitting this signal. Constitutively active MEK6 (caMEK6) increases hINV promoter activity and increases endogenous hINV levels. The caMEK6-dependent increase in gene expression is inhibited by the p38 MAPK inhibitor, SB203580, and is associated with a marked increase in p38alpha MAPK activity; JNK and ERK kinases are not activated. In addition, hINV gene expression is inhibited by dominant-negative p38alpha and increased when caMEK6 and p38alpha are co-expressed. caMEK6 also activates p38delta, but p38delta inhibits the caMEK6-dependent activation. These results suggest that MEK6 increases hINV gene expression by regulating the balance between activation of p38alpha, which increases gene expression, and p38delta, which decreases gene expression.

Previous studies suggest that a PKC/Ras/MEKK1 cascade regulates involucrin (hINV) gene expression in human epidermal keratinocytes. MEK7, which is expressed in epidermis, has been identified as a member of this cascade (Efimova, T., LaCelle, P., Welter, J. F., and Eckert, R. L. (1998) J. Biol. Chem. 273, 24387-24395 and Efimova, T., and Eckert, R. L. (2000) J. Biol. Chem. 275, 1601-1607). However, the kinase that functions downstream of MEK7 has not been identified. Our present studies show that MEK7 expression in keratinocytes markedly activates p38alpha and modestly activates JNK. Activation of p38 MAPK by MEK7 is a novel finding, as previous reports have assigned MEK7 as a JNK regulator. We also demonstrate that this regulation is physiologically important, as the p38alpha- and JNK-dependent activities regulate hINV promoter activity and expression of the endogenous hINV gene.

We have examined permeation by Ca(2+) and Ba(2+), and block by Mg(2+), using whole-cell recordings from alpha1G T-type calcium channels stably expressed in HEK 293 cells. Without Mg(o)(2+), inward currents were comparable with Ca(2+) and Ba(2+). Surprisingly, three other results indicate that alpha1G is actually selective for Ca(2+) over Ba(2+). 1) Mg(2+) block is approximately 7-fold more potent with Ba(2+) than with Ca(2+). With near-physiological (1 mM) Mg(o)(2+), inward currents were approximately 3-fold larger with 2 mM Ca(2+) than with 2 mM Ba(2+). The stronger competition between Ca(2+) and Mg(2+) implies that Ca(2+) binds more tightly than Ba(2+). 2) Outward currents (carried by Na(+)) are blocked more strongly by Ca(2+) than by Ba(2+). 3) The reversal potential is more positive with Ca(2+) than with Ba(2+), thus P(Ca) > P(Ba). We conclude that alpha1G can distinguish Ca(2+) from Ba(2+), despite the similar inward currents in the absence of Mg(o)(2+). Our results can be explained by a 2-site, 3-barrier model if Ca(2+) enters the pore 2-fold more easily than Ba(2+) but exits the pore at a 2-fold lower rate.

TIG3 is a recently discovered class II tumor suppressor protein, originally isolated from retinoid-treated cultured epidermal keratinocytes, that suppresses the proliferation of a variety of epithelial cell types. In the present study, we examine the ability of this protein to reduce CHO, T47D and HaCaT cell proliferation, and the role of the carboxy-terminal hydrophobic domain in this regulation. Vector-mediated expression of the full length TIG3 protein, TIG31-164, results in a 50-70% reduction colony formation efficiency. Expression of a truncated mutant, TIG31-134, that lacks the putative carboxy-terminal membrane-anchoring domain, results in a partial loss of ability to suppress colony formation. The fact that the truncated protein remains partially active suggests that both the amino- and carboxy-terminal regions of TIG3 are required for optimal growth suppression. The full-length protein is distributed in a perinuclear location, and is not present in the nucleus. TIG31-134, in contrast, is distributed in the cytoplasm. Thus, a change in location is associated with the partial loss of activity. We also monitored the distribution of green fluorescent protein (GFP)-TIG3 fusion proteins. GFP-TIG31-164 was localized in a pattern similar to that observed for TIG31-164, while GFP-TIG31-134 displayed a distribution pattern similar to GFP. This suggests that the c-terminal hydrophobic domain has an important role in determining the intracellular localization of TIG3. In addition, GFP-TIG31-164 retains the ability to inhibit cell function, while GFP-TIG31-134 is inactive.

The purpose of this study was to examine the current patterns of head trauma associated with child abuse. We reviewed the records of all patients admitted to our medical center between 1995 and 1997 with a primary diagnosis of head trauma, and analyzed the clinical presentation, mechanism of injury, socioeconomic status and outcome for these patients. Head trauma was deliberately inflicted in 38/405 children (9%). There were 25 boys and 13 girls, with a median age of 5.5 months. Two thirds of the families lived in the inner city. Of the 99 children under the age of 2 years admitted for head trauma, the injury was inflicted in 32 (32%). Acute subdural hematoma was present in 22/32 (69%) of children with inflicted trauma, but in only 5/68 (7%) with accidental trauma. Retinal hemorrhages were present in 17/32 (53%) abused children, but in no cases of accidental trauma (0/68). Deliberately inflicted injury is a frequent cause of serious head trauma in young children. Head injury is a major cause of morbidity and mortality in the abused child. Child abuse cases correlated strongly with low socioeconomic status. Nonaccidental trauma must be considered strongly in children under 2 years of age who present with acute subdural hematoma in the absence of a history of a motor vehicle accident., (Copyright 2000 S. Karger AG, Basel.)

Objective and Importance: Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, locally aggressive tumor that arises most commonly from the maxilla or mandible. Infrequently, it originates from the cranial vault, and recent reports have described a favorable outcome after radical surgery. Some lesions are particularly problematic, such as those located along the cranial midline or cranial base and those with significant intracranial extension. Currently, there is no effective adjuvant therapy for MNTI; radiation is precluded by the patients' young age, and chemotherapy trials have not demonstrated long-term efficacy., Clinical Presentation: A 2-month-old infant boy presented with a firm, immobile subcutaneous mass behind the right ear. The mass had been present at birth and enlarged with time., Intervention: Initial resective surgery down to the dura resulted in massive tumor recurrence within weeks. Successful management required repeat surgery including excision of the dura and dural venous sinuses., Conclusion: This patient's large MNTI of the cranial base was successfully managed by radical surgery. Although MNTI is a rapidly growing tumor that is locally highly invasive, radical surgery may be associated with a favorable outcome and offers the potential for long-term cure.