Initial Progressions of Carotid Artery Plaque Are Associated with Risk Factors of Cardiovascular Disease.

BACKGROUND: Carotid artery plaque, white matter disease (WMD), and silent lacunae infarcts (initial indicators) are associated with symptomatic cerebral infarction (CI) caused by atherosclerosis. We retrospectively examined the association between the initial indicators and risk factors for cerebrovascular disease, considering the primary prevention of symptomatic CI. METHODS: We divided 1503 individuals who were neurologically healthy and enrolled in a brain screening program (brain dock) at our institution, into three initial plaque grades (grade 0, 1, and 2) based on having no plaques, having plaques on the right or left carotid artery, or having plaques on both carotid arteries, respectively. We analyzed the risk factors according to the presence/absence of the initial indicators. RESULTS: WMD and the risk factors (low-density lipoprotein [LDL], hemoglobin A1c, systolic blood pressure [BP], and smoking cigarettes) were positively correlated with the initial plaque grades, even when their laboratory values were within normal ranges. Systolic BP (116.5 ± 14.0 mmHg) was significantly lower in group 00 (without carotid plaque and WMD) than that in age-adjusted others (with carotid plaque or WMD). In young participants aged between 40 and 52 years, LDL (132.8 ± 24.5 mg/dl) was significantly higher in subgroup ++ (with carotid plaque and WMD) compared to others (without carotid plaque or WMD). CONCLUSION: Initial plaque grade and WMD grade as clinical initial indicators of symptomatic CI are associated with risk factors. To avoid deterioration of the initial indicators, it was suggested that the risk factors should be maintained at the lower ends of normal ranges and smoking cessation should be recommended.

Mapping of flow velocity using spatiotemporal changes in time-intensity curves from indocyanine green videoangiography.

OBJECTIVE: The present study developed an image-based analysis method that uses indocyanine green videoangiography (ICG-VA) to measure flow velocity in the arteries and veins of the cortical surface in patients undergoing neurosurgery. METHODS: MATLAB-based code was used to correct motion artifacts in the ICG-VA and determine the time-intensity curve of the ICG. The slope of the initial increase in ICG intensity following the bolus injection was measured and normalized using the predicted input function in the imaging field. Flow velocity over a certain distance determined by the user was measured based on a time shift of the time-intensity curves along the centerline of the vessels. RESULTS: The normalized slope of ICG intensity represented the expected differences in the flow velocity among the artery (0.67 ± 0.05 s-1 ), parenchymal tissue (0.49 ± 0.10 s-1 ), and vein (0.44 ± 0.11 s-1 ). The flow velocities measured along the vessel centerline were 2.5 ± 1.1 cm/s and 1.1 ± 0.3 cm/s in the arteries (0.5 ± 0.2 mm in diameter) and veins (0.6 ± 0.2 mm in diameter), respectively. CONCLUSIONS: An image-based analysis method for ICG-VA was developed to map the expected differences in the flow velocity based on the rising slope of ICG intensity and to measure the absolute flow velocities using the flexible zone and cross-correlation methods.

Exploration of an Easy and Simple Method for Decompressive Craniectomy: The "Spiral Dural Incision Method".

Decompressive craniectomy (DC) is performed to alleviate intracranial hypertension as much as possible. There are two additional goals that surgeons should strive to achieve: minimization of operating time (i.e., the time issue) and avoidance of manually pushing on the surface of the bulging brain to prevent iatrogenic brain injury (i.e., "stuffing risk"). Many authors have made progress on the time issue, but stuffing risk remains largely unmitigated. We recently presented a new DC method that resolved both issues, but the incision design was too complicated for general use. A recent study has presented a duraplasty method that does not use watertight sutures and does not exacerbate the risk associated with DC. Employing the simplified method without sutures, we developed a new, easy-to-perform DC method that resolves stuffing risk. We analyzed the incision design geometrically and verified it by simulations generated with a physics engine. Three patients with massive cerebral infarction, subarachnoid hemorrhage, and hemorrhagic infarction underwent the new procedure. The targeted incision design was composed of four or five curved incision lines. Expansion of the dura resulted in transformation into a centroclinal form with spiral rifts and canopy. The dura expanded as expected in each case, and no cases required manual stuffing of the bulging brain. The operative time was acceptable, and no complications were reported. The concept of the incision design could be applied to any polygonal duraplasty in DC. We developed a new DC method that involves a simple and easily executed incision design, avoided stuffing risk.

Clinical significance of the coexistence of carotid artery plaque and white matter disease in patients with symptomatic cerebral infarction.

OBJECTIVES: Symptomatic cerebral infarction (CI) can occur in patients without main cerebral artery stenosis or occlusion. This study investigated the unique features of carotid artery plaque and white matter disease (WMD) in patients with symptomatic CI and transient ischemic attack (TIA) but without stenosis or occlusion of a main cerebral artery. PATIENTS AND METHODS: We studied 647 patients who underwent both carotid ultrasound examination and brain magnetic resonance images. Plaque score (PS), plaque number, maximal plaque intima-media thickness and grades of WMD were examined. Subjects were divided into four groups, the CI group, TIA group, myocardial infarction (MI) group and risk factor (RF) group. Plaque and WMD were analyzed in cerebral ischemia group (CI and TIA), compared to non-cerebral ischemia groups and to a high PS group and a high WMD grade group from the RF group. RESULTS: Both of each value of plaque and grades of WMD in the cerebral ischemia group were significantly higher than those in other groups. Grades of WMD in the cerebral ischemia group were significantly higher than those in the high PS group, although there was no significant difference of the each value of plaque between the two groups. The each value of plaque in the cerebral ischemia group was also significantly higher than those in the high WMD grade group, although there was no significant difference of grade of WMD between the two groups. CONCLUSION: Simultaneous increases in carotid artery plaque and WMD are associated with symptomatic CI, which is not caused by stenosis or occlusion of a main cerebral artery.

Design of a Locator for Designing the Shortest Incision for a Polygonal Dural Window.

When a wide polygonal dural window is created, a short dural incision length is preferred by surgeons because suturing a wastefully long incision line during closure is troublesome. A locator to facilitate making the shortest dural incision when creating a polygonal dural window would be helpful. We geometrically analyzed the shortest incision design for a pentagonal dural window and produced a simple locator for intraoperatively implementing this design. The design for a pentagonal dural window with the shortest incision is the same as the design for a minimum Steiner tree (MST) problem with five vertices. The MST consists of three interconnected Steiner points (SPs) with three equal, radiating branches. We produced a template of the features of the MST for a polygon (MST template) as a locator. The MST template consists of several uniform Steiner units (SUs), each of which has an SP at the center and three wings that branch off of the SP, and each SU also has three slits through which the wings of another unit can pass. This mechanism allows us to freely adjust the distance between the SPs of separate SUs. In clinical practice, we can create the shortest incision design for a quadrilateral or pentagon by arranging MST templates combining two or three SUs. If we open a wide dural window, the total incision lengths created using our method are 1-5 cm shorter than conventional incisions. The MST template accurately and easily reveals the shortest incision design.

Cochlear Nerve Action Potential Monitoring for Preserving Function of an Unseen Cochlear Nerve in Vestibular Schwannoma Surgery.

BACKGROUND: Intraoperative monitoring of cochlear nerve action potential (CNAP) has been used in patients with small vestibular schwannoma (<15 mm) to preserve cochlear nerve function. We performed surgery for a larger vestibular schwannoma under CNAP monitoring with the aim of preserving cochlear nerve function, and compared the data with findings from 10 patients with hemifacial spasm who underwent microvascular decompression surgery. CASE DESCRIPTION: We report the case of a patient with a 26-mm vestibular schwannoma and normal hearing function who underwent neurosurgery under electrophysiological monitoring of the facial and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained at approximately 70% during the operation. The latency of wave V on brainstem auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was maintained at approximately 70% of the value at the beginning of the operation. Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These latencies were comparable to those of 10 normal patients with hemifacial spasm. CNAP monitoring proved very useful in confirming the location of the cochlear nerve in the operative field and preserving cochlear nerve function. Both facial nerve function and hearing acuity were completely preserved after tumor removal, and wave V latency on BAEP returned to normal and was maintained in the normal range for at least 2 years. CONCLUSIONS: CNAP monitoring is extremely useful for preserving the function of the unseen cochlear nerve during vestibular schwannoma surgery.

Ultrasound-Guided Fine-Needle Aspiration in the Neck Region Using an Optical See-Through Head-Mounted Display: A Randomized Controlled Trial.

OBJECTIVES: The purpose of this study was to examine the feasibility of an optical see-through head-mounted display (OST-HMD) to improve ergonomics during ultrasound-guided fine-needle aspiration (FNA) in the neck region. METHODS: This randomized controlled study compared an OST-HMD with a normal ultrasound monitor during an ultrasound-guided FNA in the neck region. Patients with a neck tumor were recruited and randomized into one of two groups. Two practitioners performed ultrasound-guided FNA with or without the HMD, as indicated. An independent researcher measured the procedure time, the number and time of head movements, as well as the number of needle redirections. In addition, practitioners completed questionnaires after performing the FNA on each patient. RESULTS: In 93% of the sessions with the OST-HMD, practitioners performed ultrasound-guided FNA without turning the patients' heads. There was no difference in procedural time and number of needle redirections between the two groups. Results from the questionnaire revealed not only good wearability and low fatigue, but also the practitioners' preference for the HMD. CONCLUSIONS: The OST-HMD improved the practitioners' ergonomics and can be adopted for performing ultrasound-guided interventional procedures in clinical settings.

[A Case of Meningeal Carcinomatosis and Small Cell Lung Carcinoma Effectively Treated Using a Multidisciplinary Approach].

A 65-year-old man visited our hospital with dyspnea and cough. He was diagnosed with small cell lung carcinoma (cT4N2M1b, Stage IV). The disease partially responded to systemic chemotherapy. However, it was progressive and metastasized to the brain 3 months after 6 courses of chemotherapy. Therefore, whole brain irradiation was performed. Subsequently, weakness of the lower extremities and vesicorectal disturbances appeared. Meningeal carcinomatosis was diagnosed by enhanced magnetic resonance imaging and liquid examination. Methotrexate plus cytarabine plus dexamethasone was injected intrathecally and spinal irradiation was performed. An Ommaya reservoir was placed and intrathecal chemotherapy was continued. Systemic chemotherapy was also administered. Consequently, his symptoms improved and he was successfully discharged. Therefore, a multidisciplinary approach should be considered to improve the symptoms of patients with meningeal carcinomatosis.

Improvement of neurovascular function and cognitive impairment after STA-MCA anastomosis.

OBJECTIVE: In patients with severe steno-occlusive disease of a main cerebral artery, decreased cerebrovascular reserve (CVR) and cognitive impairment without causative focal lesions on magnetic resonance imaging have been reported. We examined ipsilateral and contralateral CVR and cognition before and after superficial temporal artery-middle cerebral artery (MCA) anastomosis operation in patients with internal carotid artery (ICA) or MCA occlusion. METHODS: In 30 patients with ICA or MCA occlusion, cognitive impairment, and decreased CVR, we examined cognition, CVR, leukoaraiosis grades, and blood data. Data from 15 patients who underwent anastomosis were compared to that in 15 patients who did not undergo anastomosis, and to bilateral data already reported on 65 patients with severe steno-occlusive disease. RESULTS: Cerebral blood flow, CVR, and cognition improved after anastomosis compared to before, and compared to patients without anastomosis; improved values were maintained for 5years. CVR recovered after anastomosis, matching the linear relationship between ipsilateral and contralateral CVR seen in the 65 patients. CONCLUSION: The postoperative improvement in cognition and synchronized recovery on the regression line between CVR of the ipsilateral occlusion and contralateral sides may suggest that the CVR is widespread and nonselectively related to cognitive function.

Exploration of the Most Effective Dural Incision Design in a Decompressive Craniectomy.

OBJECTIVE: During a decompressive craniectomy performed for a severe cerebral infarction, sufficient coverage of the underlying bulging brain by converting the flat dura mater to a more domelike shape is essential. In this procedure, suturing to patch dural substitutes on the dural rifts occupies most of the operative time and is cumbersome. We present a new dural incision design that provides an appropriate volume of subdural space with minimal incisions. METHODS: The ideal incision design was geometrically analyzed and verified by simulations using a physics engine. RESULTS: Assuming a quadrilateral area on the dura mater surface termed S, expanding the entire area of S requires 2d (where d is the skull thickness) + a 30-mm extension of the shortest set of line segments connecting each vertex (LSCV) of S to cover the necessary volume of bulging brain. The shortest LSCV comprises 5 line segments connected with two 3-pronged intersections. The ideal incision design consists of a pair of curved line segments that maintain plane continuity along the LSCV, which automatically limits the maximum expansion. The ideal incision design of S consists of 5 uncinate line segments. Four of the line segments originate from each vertex of S and end by crossing over the LSCV, and one of the line segments crosses over 2 separate LSCV. A representative case is shown. CONCLUSIONS: This technique minimizes the complexity of the operation and shortens the operation time.

Ultrasonography Monitoring with Superb Microvascular Imaging Technique in Brain Tumor Surgery.

BACKGROUND: Neuronavigation based on preoperative magnetic resonance imaging has been developed as a useful tool to improve visibility of the surgical site in the operative field. Ultrasonography (US) monitoring has also been used as a reliable imaging technique, providing real-time information during neurosurgical operations. We combined the latest innovative imaging technique for detecting very low-flow components, Superb Microvascular Imaging (SMI), with US monitoring during brain tumor surgery. CASE DESCRIPTION: Fifteen patients diagnosed with brain tumor (8 malignant and 7 benign) underwent neurosurgery with US monitoring using an Aplio 400/500 US system with the new SMI technique (imaging frequency, 10-12 MHz; frame rate, 28-31 Hz). Features of the SMI images in the gray scale mode include 1) visualization of low-velocity flow with minimal motion artifact, 2) high resolution of images, and 3) high frame rates. The tumors, tumor vessels, compressed and shifted healthy vessels, and cistern were clearly visualized on the SMI images in the gray scale mode, detailing the characteristics of healthy brain tissue (vertically penetrating, fine, straight vessels), glioblastoma (rounding, dilating, and bending vessels), low-grade glioma (fine and straight vessels), meningioma (many large and branching vessels), and lymphoma (less vascular, low echoic tumor) and demonstrating the tumor-defined border. We also performed biopsies under US monitoring with SMI. CONCLUSIONS: We combined SMI technique with US monitoring during brain tumor surgery and observed healthy and tumor vessels. Further research is important for the development of a more precise and reliable neurosurgery.

Collateral Flow and White Matter Disease in Patients with Internal Carotid Artery Occlusion.

BACKGROUND: When an internal carotid artery (ICA) occludes, a patient may develop cerebral infarction (CI). We investigated whether CI caused by ICA occlusion (ICAO) is associated with collateral flow through the anterior and posterior communicating arteries (ACoA and PCoA). METHODS: In 100 patients with ICAO, we investigated CI and white matter disease by performing an MRI and the anatomy of the ACoA and PCoA were investigated by performing magnetic resonance angiography. All patients were divided into the symptomatic CI group or the no-CI group. The collateral flow pathway was estimated by the anterior cerebral artery (ACA)-PCoA score and the collateral flow volume after ICAO was estimated by the middle cerebral artery (MCA) flow score, based on how well the MCA was visualized. RESULTS: Of 100 patients with ICAO, the symptomatic CI group included 36 patients. ACA-PCoA score and white matter disease grades were significantly higher in the CI group (indicating poor collateral flow). More than 80% of patients with an ACA-PCoA score of 4 (poor collateral) experienced symptomatic CI. Thirty-one symptomatic CI patients (86%) had an MCA flow score of 1 or 2 (decreased MCA flow). CONCLUSION: The ACA-PCoA score and white matter disease grade may suggest an increased risk of CI following ICAO.

[Analysis of initial treatment only by linac-based stereotactic radiosurgery for a metastatic brain tumor from non-small cell lung cancer].

A patient who receives stereotactic radiosurgery(SRS)alone for treating the brain metastatic lesion has a risk of tumor recurrence in the brain. Thus, some patients undergo prophylactic whole brain radiotherapy(WBRT)in addition to the SRS. However, the usefulness of adding WBRT is still debatable. In our hospitals, we initially treat metastatic brain tumors with SRS alone, and have experienced 2 long-surviving cases. Here, we report our treatment outcomes, including those for these 2 cases, and discuss the treatment plan for non-small cell lung cancer(NSCLC)with brain metastases. Forty-two brain metastatic cases were studied. Median survival(MS), tumor control rate(TCR), and recurrence ratio at distant site(RRDS)in the brain were analyzed. Age, Karnofsky performance status(KPS), and recursive partitioning analysis(RPA)class were analyzed as prognostic factors. We present 2 cases of a 42- and a 56-year-old man, surviving for more than 100 months. MS, TCR, and RRDS at 1 year in our hospitals were 20 months, 89.1%, and 25.6%, respectively. The prognostic factors were good KPS and RPA class and younger age. Our data showed a good MS among some reliable random controlled trials. Our strategy of SRS alone preserves the possibility to treat new lesions with WBRT. Prognosis was mainly defined by the systemic condition of the patient and activity of the primary lesion. Thorough treatment of the primary lesion with addition of SRS for initial treatment of metastatic lesions and scheduled MRI follow-up will provide for longer survival times.

Spontaneous occlusion of the frontal arteriovenous malformation and the following progression of the associated aneurysm: a case report.

We report the case of a 59-year-old women with a cerebral arteriovenous malformation (AVM) in the right frontal lobe, which was detected incidentally. Additionally, an aneurysm was found at the feeding artery of the AVM. The patient was treated conservatively. Nine years later, the nidus of the AVM was no longer detectable. The angiography showed the associated aneurysm growing irregularly with a daughter sac. The spontaneous occlusion of an AVM and the following progression of an associated aneurysm are rare. The possible mechanisms leading to the occlusion of the AVM and the progression of the associated aneurysm are discussed.

An R132H mutation in isocitrate dehydrogenase 1 enhances p21 expression and inhibits phosphorylation of retinoblastoma protein in glioma cells.

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1(R132H)-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1(R132H)-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progression of the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation.

Planar geometrical analysis for design of the shortest incision to open the dura mater: technical note.

Quadrilateral dural window is opened with a conventional incision design, such as a pair of diagonal lines or a rectangular shape, but the total cutting length is not the shortest possible. Shorter incision length will have a lower risk of dysraphia associated with cerebrospinal fluid (CSF) liquorrhea or related CSF infection. We propose a new and effective dural incision design with the shortest cutting length for quadrilateral dural openings. We investigated the design of the dural incision using a simple planar geometrical figure. We discovered the shortest network design to connect the four vertices of the quadrilateral. The shortest network design was formed of five line segments with two three-pronged interconnections (TPIs) with the same angle of 2π/3 between any two lines (2π/3-TPI). In practice, first we must draw a quadrilateral W horizontally then add two equilateral triangles outside W. Using a 2π/3-bent wire, the 2π/3-TPIs are traced on the path connecting the outward vertices of the equilateral triangles. Using this method, we can reduce the incision length by 10% from conventional designs using a pair of diagonal lines.

Role of blood cell-associated angiotensin II type 1 receptors in the cerebral microvascular response to ischemic stroke during angiotensin-induced hypertension.

BACKGROUND: Angiotensin II type 1 receptor (AT1R) blockers lower the incidence of ischemic stroke in hypertensive patients and attenuate brain inflammation and injury in animal models. Although AT1R on both blood cells (BC) and vascular endothelial cells (EC) can be activated by angiotensin II (Ang II) to elicit inflammation, little is known about the relative contributions of AT1R expressed on BC and EC to the brain injury responses to ischemia and reperfusion (I/R) in the setting of angiotensin-induced hypertension. METHODS: The contributions of BC- and EC-associated AT1R to I/R-induced brain inflammation and injury were evaluated using wild type (WT), AT1aR-/-, and bone marrow chimera mice with either a BC+/EC+ (WT→WT) or BC-/EC+ (AT1aR-/-→WT) distribution of AT1aR. The adhesion of leukocytes and platelets in venules, blood brain barrier (BBB) permeability and infarct volume were monitored in postischemic brain of normotensive and Ang II-induced hypertensive mice. RESULTS: The inflammatory (blood cell adhesion) and injury (BBB permeability, infarct volume) responses were greatly exaggerated in the presence of Ang II-induced hypertension. The Ang II-enhanced responses were significantly blunted in AT1aR-/- mice. A similar level of protection was noted in AT1aR-/- →WT mice for BBB permeability and infarct volume, while less or no protection was evident for leukocyte and platelet adhesion, respectively. CONCLUSIONS: BC- and EC-associated AT1aR are both involved in the brain injury responses to ischemic stroke during Ang II-hypertension, with EC AT1aR contributing more to the blood cell recruitment response and BC AT1aR exerting a significant influence on the BBB disruption and tissue necrosis elicited by I/R.

Mechanisms underlying the cerebral microvascular responses to angiotensin II-induced hypertension.

Angiotensin II (AngII) and AngII type-1 receptors (AT1r) have been implicated in the pathogenesis of hypertension and ischemic stroke. The objectives of this study was to determine if/how chronic AngII administration affects blood-brain barrier (BBB) function and blood cell adhesion in the cerebral microvasculature. AngII-loaded osmotic pumps were implanted in wild type (WT) and mutant mice. Leukocyte and platelet adhesion were monitored in cerebral venules by intravital microscopy and BBB permeability detected by Evans blue leakage. AngII (two week) infusion increased blood pressure in WT mice. This was accompanied by an increased BBB permeability and a high density of adherent leukocytes and platelets. AT1r (on the vessel wall, but not on blood cells) was largely responsible for the microvascular responses to AngII. Immunodeficient (Rag-1(-/-) ) mice exhibited blunted blood cell recruitment responses without a change in BBB permeability. A similar protection pattern was noted in RANTES(-/-) and P-selectin(-/-) mice, with bone marrow chimeras (blood cell deficiency only) yielding responses comparable to the respective knockouts. These findings implicate AT1r in the microvascular dysfunction associated with AngII-induced hypertension and suggest that immune cells and blood cell-associated RANTES and P-selectin contribute to the blood cell recruitment, but not the BBB failure, elicited by AngII.

Benefits of clipping surgery based on three-dimensional computed tomography angiography.

The recent development of three-dimensional computed tomography (3D-CT) angiography with multi detector row CT (MDCT) improves cerebral artery imaging due to faster scanning at thinner collimation over a large scanning volume. Aneurysm clipping was performed using only 3D-CT angiography created by MDCT with 16 detector arrays (16-MDCT angiography), in place of digital subtraction angiography (DSA) to evaluate the suitability of 16-MDCT angiography for preoperative examination before aneurysm clipping, and identify the essential points when making 3D images. Thirty-two patients with subarachnoid hemorrhage (SAH) identified by initial CT or with non-ruptured aneurysm were entered in this study. Twenty-six SAH patients underwent 3D-CT angiography, and aneurysms were treated by clipping (n = 25) or coil embolization (n = 4). One patient with no aneurysm depicted by 3D-CT angiography underwent conventional DSA twice subsequently. The sensitivity of 16-MDCT angiography to depict aneurysms in patients with SAH, and time between admission and entering the operating room were evaluated, and compared with those under the former protocol using DSA. The sensitivity of 16-MDCT angiography for aneurysm detection was 100%. Shapes of all aneurysms depicted by 3D-CT angiography were validated intra-operatively. The mean operation waiting time was 2.8 hours, with the shortest time being 1.5 hours. Re-bleeding occurred in one of the 20 patients. We conclude that shorter preoperative waiting time decreased the incidence of premature re-bleeding, resulting in better outcomes. We highly recommend that the surgeon sets the threshold value, and rotates the 3D image to establish better surgical orientation.

Role of coagulation factors in cerebral venous sinus and cerebral microvascular thrombosis.

OBJECTIVE: The objective of this study was to define the relative contributions of three major pro- and anti-coagulation pathways (heparin-antithrombin, protein C, and tissue factor (TF)) in the thrombogenic responses that occur in large and small vessels of the brain. METHODS: Cerebral venous sinus thrombosis was induced by topical application of FeCl3 on the superior sagittal sinus, while photoactivation of fluorescein was used to induce thrombus formation in cerebral microvessels. Heparin, activated protein C (APC), and antibodies to either APC or TF were used to assess thrombogenesis in wild-type mice. Mutant mice that overexpress the endothelial protein C receptor (EPCR-tg) or with TF deficiency in Tie2-expressing endothelial cells (LTFE) were also used. RESULTS: Thrombus formation in the superior sagittal sinus of wild-type mice was attenuated by heparin and in EPCR-tg mice, while treatment with the APC antibodies enhanced thrombogenesis. Arteriolar thrombosis was largely unresponsive to the interventions studied. However, in cerebral venules, thrombosis was inhibited by heparin and in EPCR-tg mice. TF antibody treatment also inhibited venular thrombosis, with a similar attenuation noted in LTFE mice. CONCLUSION: Thrombin promotes while the APC pathway blunts thrombus formation in an experimental model of cerebral venous sinus thrombosis. TF involvement is more evident in cerebral microvascular thrombogenesis, with endothelial cell-associated TF mediating this response in venules, but not arterioles.