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Objective: This is the first report of a ruptured aneurysm involving a collateral branch to the posterior inferior cerebellar artery (PICA) in a patient who had a subarachnoid hemorrhage., Clinical Presentation: A 56-year-old man initially presented with a subarachnoid hemorrhage and underwent 2 catheter-based 4-vessel angiograms with negative results. A delayed angiogram 4 weeks later revealed a dissecting aneurysm of the posterior meningeal artery, a branch of the vertebral artery., Intervention: A 3-dimensional reconstruction of the vertebral angiogram showed proximal occlusion of the proximal left PICA and distal filling via a collateral branch from the posterior meningeal artery. A far-lateral approach was used for this patient. The aneurysm was found along the course of the collateral posterior meningeal artery and was clipped successfully., Conclusion: Aneurysms involving collateral branches of the PICA are rare. It is important to recognize such collateral flow preoperatively because inadvertent sacrifice of these vessels during a surgical approach could lead to stroke and neurological deficits of the PICA territory.

Background: The efficacy of intravenous (IV) alteplase is restricted by the speed of recanalisation and the site of the occlusion. The aim of this study was to ascertain the effect of a combined IV-endovascular approach (intra-arterial alteplase and, if required, additional thrombectomy) in patients with stroke due to arterial occlusion., Methods: We compared recanalisation rates, neurological improvement at 24 h, and functional outcome at 3 months between two periods (February, 2002, to March, 2007, vs April, 2007, to October, 2008) in patients in a prospective registry who were treated with different regimens of alteplase within 3 h of symptom onset. Patients with confirmed occlusion who were treated before April, 2007, were treated with IV alteplase; after April, 2007, patients were treated with a systematic IV-endovascular approach. Analysis was by intention to treat., Findings: 46 (87%) of 53 patients treated with the IV-endovascular approach achieved recanalisation versus 56 (52%) of 107 patients in the IV group (adjusted relative risk [RR] 1.49, 95% CI 1.21-1.84; p=0.0002). Early neurological improvement (NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h) occurred in 32 (60%) patients in the IV-endovascular group and 42 (39%) patients in the IV group (adjusted RR 1.36, 0.97-1.91; p=0.07). Favourable outcome (mRS of 0-2 at 90 days) occurred in 30 (57%) patients in the IV-endovascular group and 47 (44%) patients in the IV group (adjusted RR 1.16, 0.85-1.58; p=0.35). The mortality rate at 90 days was 17% in both groups, and symptomatic intracranial haemorrhage was reported in five (9%) patients in the IV-endovascular group and in 12 (11%) patients in the IV group. Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV-endovascular group., Interpretation: An IV-endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion. In patients treated with an IV-endovascular approach, a shorter time from symptom onset to recanalisation is associated with better clinical outcomes.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired bone-marrow disorder characterized by hemolytic anemia, hemoglobinuria, and cytopenia. Most patients die from venous thrombotic events. Stroke is a common cause of morbidity and mortality in PNH and it is almost exclusively a result of cerebral venous thrombosis. Case reports of ischemic stroke complicating PNH have implicated a similar propensity for arterial events caused by the disease. We present a case of recurrent cerebral infarctions complicating PNH initially attributed to arterial thrombosis but ultimately determined to be a result of the disease and a concomitant patent foramen ovale identified only after repeated evaluations. This case emphasizes the pitfalls of diagnostic testing and the importance of a persistent search for a venous cause for cerebral embolic events in patients with hematologic diseases not classically known to involve the arterial system.

Whether Rho-kinase activity is really associated with the pathogenesis of cerebral infarction remains unclear. To consider this question, we investigated correspondences between severity of neurological deficit, infarct size, amount of various marker proteins, and Rho-kinase activity in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere in rats. We prepared rats with various severities of neurological deficit (mild to severe) 3 days after injection of laurate, then measured infarct size and amount of various marker proteins, phosphorylation of substrates of Rho-kinase, myosin-binding subunit (MBS), myosin light chain (MLC), ezrin/radixin/moesin (ERM), and adducin using Western blot methods. First, infarct size increased corresponding to the severity of neurological deficit. Second, amounts of activating transcription factor 3, nestin, CD68, proliferating cell nuclear antigen, and heat shock protein 70 were increased, whereas neurofilament and myelin-associated glycoprotein were decreased corresponding to the severity of neurological deficit and infarct size. Finally, Rho-kinase activity (phospho-MBS/MBS, phospho-MLC/MLC, phospho-ERM/ERM, and phospho-adducin/adducin) was increased corresponding to the severity of neurological deficit and infarct size. Rho-kinase thus appears to play a crucial role in the pathogenesis of cerebral infarction.

Background and Purpose: The purpose of this clinical evaluation was to assess the safety and effectiveness of the Penumbra System in the revascularization of patients presenting with acute ischemic stroke secondary to intracranial large vessel occlusive disease., Methods: In this prospective, multicenter, single-arm study, 125 patients with neurological deficits as defined by a National Institutes of Health Stroke Scale score > or =8, presented within 8 hours of symptom onset, and an angiographic occlusion (Thrombolysis In Myocardial Infarction [TIMI] Grade 0 or 1) of a treatable large intracranial vessel were enrolled. Patients who presented within 3 hours from symptom onset had to be ineligible or refractory to recombinant tissue plasminogen activator therapy. All patients were followed clinically for 90 days postprocedure., Results: A total of 125 target vessels in 125 patients were treated by the Penumbra System. Postprocedure, 81.6% of the treated vessels were successfully revascularized to TIMI 2 to 3. There were 18 procedural events reported in 16 patients (12.8%), 3 patients (2.4%) had events that were considered serious. A total of 35 patients (28%) were found to have intracranial hemorrhage on 24-hour CT of which 14 (11.2%) were symptomatic. All cause mortality was 32.8% at 90 days with 25% of the patients achieving a modified Rankin Scale score of < or =2., Conclusions: These results suggest the Penumbra System allows safe and effective revascularization in patients experiencing ischemic stroke secondary to large vessel occlusive disease who present within 8 hours from symptom onset.

Background: Basilar artery thrombosis remains a significant clinical problem, and no reproducible animal model has been established to study the stroke within the vertebrobasilar distribution. We report a study designed to pilot test a novel model of brainstem stroke in rabbits, created by selective endovascular occlusion of the basilar artery., Methods: Basilar artery occlusion was induced in 8 New Zealand white rabbits by injection of the autologous clot through the microcatheter positioned within the distal vertebral artery. Animals were divided into subgroups (I and II) based on the length of produced ischemia (3 and 6 hours, respectively). Magnetic resonance (MR) imaging of the brain and MR angiography of the intracranial vessels were performed before the procedure, and at 3 hours after induced ischemia for groups I and II, with continued imaging up to 6 hours for group II, with diffusion-weighted images acquired approximately every 30 minutes. Animals were killed at the end of the 3-hour (group I) or 6-hour (group II) ischemia time., Results: Brainstem stroke was successfully induced in all animals, with pathological changes documented in all cases. The earliest changes of ischemia on MR diffusion-weighted images were identified at only 4.5 hours of basilar artery occlusion., Conclusion: These results suggest that a reproducible model of brainstem stroke can be induced in rabbits using selective endovascular occlusion of the basilar artery. The availability of such a model, integrated with state-of-the-art imaging techniques, holds promise for preclinical investigations of emergent therapeutic approaches in stroke.

We present data concerning the extraction of clots using the newly invented "GP" mechanical thrombectomy device (MTD). Artificial and porcine clots of various lengths were used in plastic tube models of an artery. We investigate the pressures and times taken for clot extraction together with the volumes of fluid extracted. We also investigate the impact of using a funnel structure mounted on the end of the device, on clot removal times and fluid removed. Finally, we present results involving clot extraction from the posterior popliteal artery of a cadaver. Our data indicated that: The embedded GP MTD is the most effective device regarding artificial and porcine blood clot removal. This result is consistent with previous published data on this device. The GP MTD was effective in removing clots positioned in the posterior popliteal artery of a cadaver. The embedded GP device removes less fluid compared with the end-mounted GP device. This confirms previous studies. There appears to be a relationship between funnel angle and pressure. Lower extraction pressures are required for larger funnel angles mounted on the GP device. Shorter times of clot extraction are required for larger funnel angles.

Background: Lacunar stroke accounts for a quarter of cases of acute ischaemic stroke; however, its underlying pathophysiology remains unclear. Our aim was to establish whether there is an association between changes in the retinal microvasculature and lacunar stroke that might provide clues to the pathology of cerebral small vessel disease., Methods: In this cross-sectional study, we recruited patients who presented with acute stroke at three centres in two countries (Sydney and Melbourne, Australia, and Singapore). Each patient had standardised clinical assessments, retinal photography, and CT or MRI of the brain. Changes in the retinal microvasculature were assessed from retinal photographs by graders who were masked to the patients' clinical details. Lacunar stroke was diagnosed according to a modified version of the TOAST criteria (Treatment of Acute Stroke Trial) or the OCSP criteria (Oxfordshire Community Stroke Project) and by MRI findings., Findings: We recruited 1321 patients aged 19 to 94 years with acute ischaemic stroke; 410 (31%) had lacunar stroke. Patients with acute lacunar stroke were no more likely to have hypertension (p=0.12), diabetes (p=0.51), or hypercholesterolaemia (p=0.91) than were patients with other types of ischaemic stroke. However, patients with lacunar stroke were more likely to have retinal microvessel signs, particularly when stroke subtype was confirmed using diffusion-weighted MRI, than were patients with other stroke subtypes. After adjustment for age, sex, study site, smoking history, hypertension, and diabetes, the patients with lacunar stroke were more likely than those with other stroke subtypes to have microvessel signs, and when stroke subtype was confirmed by diffusion-weighted MRI the odds ratios were: 3.55 (95% CI 1.77-7.12) for focal arteriolar narrowing; 1.96 (1.19-3.24) for arteriovenous nipping; 2.32 (1.42-3.79) for enhanced light reflex of the arteriolar wall; 1.33 (0.74-2.41) for generalised retinal arteriolar narrowing; 1.45 (0.84-2.51) for small retinal arteriole:venule ratio; and 1.35 (0.80-2.26) for retinal venular widening., Interpretation: Our findings suggest that acute lacunar stroke is a manifestation of non-atherothrombotic occlusive small vessel disease, which might have implications for the prevention and treatment of this stroke subtype., Funding: National Health and Medical Research Council of Australia; National Medical Research Council of Singapore; Scottish Funding Council; New South Wales Health.

An 11-year-old female receiving treatment for acute lymphoblastic leukemia presented with superior sagittal sinus (SSS) thrombosis. T(1)-weighted, T(2)-weighted, and fluid-attenuated inversion recovery magnetic resonance (MR) imaging, and MR venography showed that the SSS was totally occluded by thrombus. Susceptibility-weighted MR imaging showed hypointense thrombus in the SSS and markedly dilated cortical veins over the bilateral cerebral hemispheres. Two days later, her symptoms had slightly resolved. Iodine-123 N-isopropyl-p-iodoamphetamine single photon emission computed tomography showed marked decrease of cerebral blood flow in the bilateral frontal lobes, indicating that venous congestion had disturbed the cerebral hemodynamics. MR venography showed that the SSS was still mostly occluded, but susceptibility-weighted imaging showed that the dilation of the cortical veins was less marked, suggesting that collateral venous routes had gradually developed. The finding of dilated cortical veins had almost disappeared at 28 days after the onset. Susceptibility-weighted imaging can be used as a non-invasive method to monitor the severity of venous congestion caused by cerebral venous sinus thrombosis.

The alterations of the cerebral venous circulation are a rare but clinically important cause of headache. Although any process involving the cerebral veins or sinuses may cause headache, the most frequent and important are cerebral venous thrombosis and idiopathic intracranial hypertension. The headache of cerebral venous thrombosis does not have specific features and may be isolated; therefore, all patients with headache and risk factors for venous thrombosis should undergo the appropriate neuroradiologic examinations to rule out the diagnosis. In fact, early anticoagulant treatment may dramatically change the clinical outcome. Also idiopathic intracranial hypertension, if untreated, may have serious clinical consequences such as permanent visual loss. The pathogenesis of this disorder has not been clearly established and several possibilities involving the cerebral circulation are discussed.

Background: Parent artery occlusion (PAO) is an alternative surgical strategy for complex internal carotid artery (ICA) aneurysms, which are unclippable because of their anatomical structures, including a broad neck, fragile dome, critical branch, and cavernous sinus location. Despite revascularization, ischemic complications occur after the PAO because of several factors, such as hypoperfusion, embolism, and perforator impairment., Methods: Acute ischemic complications and their mechanisms were analyzed in a consecutive series of 32 patients presenting with complex ICA aneurysms treated by PAO., Results: Fourteen ruptured and 18 unruptured aneurysms were located in the cavernous sinus (n = 16) and paraclinoid portion (n = 16). Preoperative balloon test occlusion was performed to investigate ischemic tolerance and to select the bypass method in 24 cases. An extracranial-intracranial bypass was constructed using the superficial temporal artery in 17, and a saphenous vein graft was done in 12 cases. Although postoperative hypoperfusion was prevented by revascularization based on the balloon test occlusion, acute ischemic complications due to perforator occlusion and thromboembolism were observed in 10 cases after the surgery. Five cases presented with impairment of perforating branches adjacent to the occluded parent artery, resulting in prolonged neurologic deterioration., Conclusion: The distal location of ICA aneurysms is a risk factor for the perforator impairment, when treated by PAO, and PAO by clip placement is preferred to endovascular coiling to prevent of perforator impairment.

Background: Temporary occlusion of an intracranial artery during microvascular anastomosis is a major risk factor in cerebrovascular surgery. A new laser vascular welding technique that minimizes the occlusion time of the recipient vessel has been developed and is described in this report., Method: A new minimally occlusive technique of end-to-side microvascular anastomosis was developed employing a diode laser in association with the application of a chromophore in our experimental model of double end-to-side anastomosis. The implantation of a vein graft on the patent carotid artery was obtained through the application of three interrupted sutures at each anastomotic site; the carotid was then clamped, two arteriotomies were performed, followed by the application of a fourth suture and of the laser welding procedure on each anastomosis. Monitoring of the temperature at the site of the anastomosis was introduced in order to control the welding technique., Findings: The time of the clamping of the carotid artery was 12 min to perform two end-to-side anastomoses (i.e., 6 min for each anastomosis). All bypasses were patent after a follow-up of 90 days and histological study confirmed good preservation of the vascular wall., Conclusions: Our laser-assisted technique of vascular anastomosis reduces the duration of the clamping of the recipient artery down to 6 min. This technique can minimize the risk of cerebral ischemia associated with occlusion of a recipient artery in intracranial bypass procedures, promoting an improved vascular healing process with a lower risk of thrombosis and occlusion.

Acute ischemic stroke results from an abrupt interruption of focal cerebral blood flow. In the majority of cases, this interruption is caused by an acute thromboembolism. Arising from the clinical trials in acute myocardial infarction, combination pharmacotherapy is gaining significant interest as a potential method to improve current thrombolytic treatment in acute ischemic stroke. This article reviews the scientific rationale and available evidence for the potential options to improve current pharmacologic therapy for achieving and maintaining vascular patency in acute ischemic stroke.

Background and Purpose: Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH) are commonly encountered on MR imaging studies performed shortly after the onset of acute ischemic stroke. Prior reports have speculated regarding the pathogenesis of this finding, yet definitive correlative angiographic studies have not been performed. We studied the pathophysiologic and hemodynamic correlates of FVH on conventional angiography and concurrent MR imaging sequences., Materials and Methods: Retrospective review of FLAIR and gradient-refocused echo MR imaging sequences acquired immediately before conventional angiography for acute stroke was conducted in a blinded fashion. The presence, location, and morphology of FVH were noted and correlated with markers of thrombotic occlusion and collateral flow on angiography. Angiographic collaterals were graded on a 5-point scale incorporating extent and hemodynamic aspects., Results: A prospective ischemic stroke registry of 632 patients was searched to identify 74 patients (mean age, 63.4 +/- 20 years; 48% women) having undergone FLAIR sequences immediately before angiography. Median time from FLAIR to angiography was 2.9 hours (interquartile range, 1.1-4.7 hours). FVH were present in 53/74 (72%) of all acute stroke cases with subsequent angiography. FVH distal to an arterial occlusion were associated with a high grade of leptomeningeal collateral blood flow., Conclusions: FVH are observed in areas of blood flow proximal and distal to stenosis or occlusion and are noted with more extensive collateral circulation.

Cerebral venous thrombosis is a rare cause of stroke. Clinical presentation is not very specific and can be very variable. Imaging establishes the diagnosis in the majority of cases. Specially, magnetic resonance venography has high sensitivity and is presently the gold standard. Long term prognosis of cerebral venous thrombosis is generally good and few patients remain handicapped in the long term. Evolution is however unpredictable. Treatment strategies follow three axes: anti-thrombotic treatment, symptomatic measures and treatment of the cause if one is found.

Background and Purpose: Basal ganglia infarction is typically caused by the occlusion of deep arteries and the formation of relatively small lesions called lacunes. In the present study, a rat model of lacunar infarction was induced by photothrombotic occlusion of the small vessels within the caudate-putamen and subsequently characterized., Methods: Male Sprague-Dawley rats (n=143) were anesthetized, and Rose Bengal dye (20 mg/kg) was intravenously injected. The left caudoputamen was exposed to cold white light for 5 to 10 minutes via a stereotaxically implanted polymethylmethacrylate optic fiber (0.5-0.75 mm diameter). Neurological and morphological changes were assessed at various times during the following 6 weeks. Local cerebral blood flow was measured 90 minutes after photothrombosis by [(14)C]-N-isopropyl-p-iodoamphetamine quantitative autoradiography. The time course of blood-brain barrier opening and ischemic brain edema as well as the effects of aspirin and tissue plasminogen activator treatment were also determined., Results: A virtually round infarct with thrombosed parenchymal vessels surrounded by a layer of selective neuronal death was formed within the caudoputamen; it turned into a cystic cavity (lacune) over 6 weeks. A central zone of markedly reduced blood flow and surrounding oligemic zone were observed 90 minutes after light exposure. Lesion size was proportional to light exposure, and the severity and duration of neurological deficits paralleled infarct size. Early blood-brain barrier opening with edema peaked at day 1. After tissue plasminogen activator treatment, infarction volume and neurological deficits were reduced., Conclusions: This study describes a new rat model of lacunar infarction by photothrombotic occlusion of the microvessels within the caudoputamen. With this model, infarct size correlates with the severity and duration of the neuropathology and can be varied by altering light exposure.

Cor triatriatum (CT) is a rare congenital heart disease characterized by a fibromuscular membrane that divides the left atrium into two distinct chambers and mostly manifests during infancy mimicking mitral valve stenosis. We present the uncommon case of cardioembolic ischemic stroke in an adult man on the grounds of an otherwise asymptomatic CT with intra-atrial thrombus formation, which was established by means of transesophageal echocardiography and cardiac magnetic resonance imaging. Because exact diagnosis and surgical treatment is feasible, we suggest CT as a rare, but potentially treatable source of cerebral embolism in adult patients with stroke and dilatated left atrium.

Early reperfusion therapy for acute stroke, similar to acute myocardial infarction, has the best opportunity to reduce morbidity and mortality. Treatment options include intravenous (IV) thrombolysis therapy and/or catheter-based therapy (CBT). Catheter-based therapies include local intra-arterial thrombolysis, mechanical thrombectomy, and angioplasty techniques. Intravenous thrombolysis is limited to the first three hours after symptom onset, which excludes many patients with disabling stroke deficits. Catheter-based therapy is effective up to seven hours after onset, but availability is limited by the lack of neurointerventionalists available around the clock to provide this care. To increase the number of providers for acute stroke reperfusion therapy, we have formed a multidisciplinary team to take advantage of cardiologists' carotid stent placement experience to provide continuous coverage for emergency reperfusion therapy. We present two cases of acute stroke treated with CBT by interventional cardiologists., ((c) 2008 Wiley-Liss, Inc.)

Background: Hyperacute surgical evacuation of intracerebral hemorrhage is associated with a high rebleeding rate. The peri-operative administration of rFVIIa to patients with intracerebral hemorrhage may decrease the frequency of post-operative hemorrhage, and improve outcome., Methods: Patients receiving recombinant activated factor VII (rFVIIA) therapy immediately prior to acute surgery were collected at two centres. The intracerebral hemorrhage (ICH) score and ICH Grading Scale were determined, as was long-term outcome using the modified Rankin Scale. Residual/recurrent clot was evaluated by comparing pre-operative to post-operative CT scans., Results: Fifteen patients with intracerebral hemorrhage received 40-90 microg/kg of rFVIIa and underwent surgical hematoma evacuation at a median time of five hours following symptom onset. Median pre-operative clot volume was 60 ml, decreasing to 2 ml post-operatively. There were no thromboembolic adverse events. Thirteen patients survived, 11 (73%) were independent, and two (13%) had a moderate to severe disability. These outcomes were significantly better than expected based on the median ICH score (40% mortality) and based on median ICH Grading Scale (18% good outcome)., Conclusions: The pre or perioperative administration of rFVIIa resulted in minimal residual or recurrent hematoma volume and may be an important adjunct to surgery in patients with intracerebral hemorrhage.

In ischemic stroke, treatment options are limited. Therapeutic thrombolysis is restricted to the first few hours after stroke, and the utility of current platelet aggregation inhibitors, including GPIIb/IIIa receptor antagonists, and anticoagulants is counterbalanced by the risk of intracerebral bleeding complications. Numerous attempts to establish neuroprotection in ischemic stroke have been unfruitful. Thus, there is strong demand for novel treatment strategies. Major advances have been made in understanding the molecular functions of platelet receptors such as glycoprotein Ib (GPIb) and GPVI and their downstream signaling pathways that allow interference with their function. Inhibition of these receptors in the mouse stroke model of transient middle cerebral artery occlusion prevented infarctions without increasing the risk of intracerebral bleeding. Similarly, it is now clear that the intrinsic coagulation factor XII (FXII) and FXI play a functional role in thrombus formation and stabilization during stroke: their deficiency or blockade protects from cerebral ischemia without overtly affecting hemostasis. Based on the accumulating evidence that thrombus formation and hemostasis are not inevitably linked, new concepts for prevention and treatment of ischemic stroke may eventually emerge without the hazard of severe bleeding complications. This review discusses recent advances related to antithrombotic strategies in experimental stroke research.

An 86-year-old man with a history of brain infarction was admitted because of recurrent stroke with symptoms of left hemiparesis. Ultrasonography revealed a mobile thrombus in the brachiocephalic artery. Although anticoagulant therapy was commenced, neurologic symptoms deteriorated suddenly and he died on the third day. Autopsy indicated that the thrombus resulted from plaque rupture in the brachiocephalic artery.

Objective: This study examined the growth potential and response to multimodality treatment of partially thrombosed large or giant aneurysms in the posterior circulation., Methods: The 17 aneurysms arose from nonbranching sites of the vertebral artery (VA) in 6 patients and from branching sites in 11 patients (the VA-posteroinferior cerebellar artery [PICA], 3 cases; basilar artery [BA] fenestration, 1 case; BA-superior cerebellar artery [SCA], 5 cases; and BA tip, 2 cases)., Results: Endovascular trapping was performed in 5 VA aneurysms at nonbranching sites, 2 VA-PICA cases with or without revascularization of the PICA, and 1 BA fenestration case. Endosaccular embolization was performed in 2 BA-SCA aneurysms as the sole treatment or after superficial temporal artery-SCA bypass for a broad-necked lesion. Surgical proximal occlusion (PO) with or without revascularization of the PICA was performed in 2 VA cases. Endovascular treatment failed to prevent growth in 1 VA-PICA case and the broad-necked BA-SCA case. Simple flow alteration by PO of 3 BA aneurysms, with gadolinium enhancement on T1-weighted images, did not prevent growth. Maximum flow reduction by various combinations of bypass (superficial temporal artery-posterior cerebral artery or superficial temporal artery-SCA) and BA PO, aimed at reducing hemodynamic stress on the neck, was tailored to 5 cases, including those refractory to PO; it achieved marked shrinkage in 2 cases and stabilization of the aneurysms in 3 cases. The aneurysms harboring neither gadolinium enhancement nor hyperintensity on fluid-attenuated inversion recovery images showed significantly lower growth potential before treatment and a lesser degree of shrinkage after tailored treatment than the remaining cases (P = 0.03 and P = 0.01, respectively). Overall, marked shrinkage was achieved in 27%, moderate shrinkage in 20%, stabilization in 47%, enlargement in 7%, and favorable outcome in 71%. Maximum flow reduction strategy for BA aneurysms tended to show higher shrinking efficacy than endovascular trapping for VA and BA aneurysms (P = 0.08)., Conclusion: For aneurysms at nonbranching sites, endovascular trapping may be effective, although its shrinking efficacy may be moderate. For the most formidable BA aneurysms at branching sites, maximum flow reduction may cause marked shrinkage, even of aggressive lesions.

Background and Purpose: The natural history, causative factors, and outcomes of patients with cerebral venous thrombosis from Asia and Middle East have not been well described. This descriptive multicenter study describes the results for cerebral venous thrombosis patients in South Asia and the Middle East., Methods: The retrospective and prospective data of patients with radiologically confirmed cerebral venous thrombosis were collected from 4 centers located in Pakistan and United Arab Emirates. The demographic, clinical, radiological, and outcome data were recorded and analyzed. Primary outcome was death or dependency (modified Rankin score >2) at the time of hospital discharge., Results: This study included 109 patients with cerebral venous thrombosis; the presenting features most commonly being observed were headache (81%), focal motor deficits (45%), seizures (39%), and mental status changes (37%). Important predisposing factors included systemic and central nervous system infection (18%), postpartum state (17%), hyperhomocystinemia (9%), genetic thrombophilia (5%), and oral contraceptive pill use (3%). Ninety-six (67%) patients received therapeutic anticoagulation. Seven patients died and 43 had poor outcome at discharge. Focal motor deficits (OR, 2.93; 95% CI, 1.2-7.5; P=0.018) and hemorrhagic infarctions (OR, 2.81; 95% CI, 1.04-7.85; P=0.041) were independent predictors of unfavorable outcome at discharge. Hemorrhagic infarction was the most significant factor of long-term unfavorable outcome (OR, 5.87; 95% CI, 1.49-23.02; P=0.011)., Conclusions: Infections and postpartum state were the most common predisposing factors for cerebral venous thrombosis in this cohort. Most patients (67%) were treated with anticoagulation therapy. Almost 50% of patients were dead or disabled at discharge.

Background: Large studies of patients with acute stroke not receiving thrombolytic therapy have repeatedly demonstrated poorer outcomes for women compared to men. An analysis of five pooled randomized controlled trials testing IV recombinant tissue plasminogen activator (rtPA) demonstrated that rtPA benefits women more than men; the usual gender difference, apparent among controls, was totally nullified in the rtPA group. This nullification of the usual gender effect among rtPA-treated patients has not been confirmed., Methods: We analyzed baseline characteristics and functional outcomes in men vs women in the Canadian Alteplase for Stroke Effectiveness Study (CASES), a multicenter study that collected outcomes data for patients treated with rtPA in Canada to assess the safety and effectiveness of alteplase for stroke in the context of routine care., Results: Among 1,110 patients, including 615 men and 505 women, a normal or near normal outcome at 90 days was found in 37.1% of men vs 36.0% of women (p = 0.71). This was essentially unchanged after adjusting for differences in baseline characteristics, including age >70, glucose, hypertension, atrial fibrillation, hypercholesterolemia, baseline National Institute of Health Stroke Severity, and baseline Alberta Stroke Program Early CT score (35.2% in men vs 38.2% in women, p = 0.332). Ninety-day mortality was similar between the sexes in both the adjusted and unadjusted analysis., Conclusions: There was no difference in 90-day outcomes in recombinant tissue plasminogen activator (rtPA)-treated men and rtPA-treated women. This is consistent with the pooled analysis of randomized controlled trials, showing greater benefit for thrombolysis in women and nullification of the usual gender difference in outcome.

Ruptured vertebrobasilar dissecting aneurysm is usually treated surgically because rebleeding negatively affects outcome. However, the risk of rebleeding decreases markedly once several hours have passed from the initial bleeding. Moreover, surgery-related complications are not rare. We describe seven patients with ruptured vertebrobasilar dissecting aneurysm. To prevent rebleeding during the acute stage, we treated all seven patients conservatively with fentanyl instead of emergency surgery. During the follow-up period (mean 20 months), no patient suffered rebleeding. Conservative treatment with fentanyl administration may be a good option for management of ruptured vertebrobasilar dissecting aneurysm during the acute stage.

Objective: To search for the best way to elevate the clinical therapeutic effect in the hemiplegic patient of cerebral thrombosis at convalescent period., Methods: Adopting single-blind, randomized controlled method, 90 cases of cerebral thrombosis at convalescent period were assigned to 3 groups: a scalp acupuncture group (group A), a rehabilitation therapy group (group B) and a scalp acupuncture combined with rehabilitation therapy group (group C). Group A were treated with scalp acupuncture at the anterior oblique line of vertex-temporal and the posterior oblique line of vertex-temporal on the healthy side; group B were treated with modern rehabilitation medical therapy, making limb function treatment; group C were treated with the scalp acupuncture in the group A combined with the rehabilitation therapy in the group B. Improvement of neural function defect and activity of daily life (ADL), and clinical therapeutic effect were observed., Results: After treatment, the scores of neural function defect of 6.14 +/- 0.36 in the group C was significantly lower than 8.94 +/- 0.56 in the group A and 8.64 +/- 0.49 in the group B (P<0.05); the score of ADL of 88.39 +/- 10.02 and clinical therapeutic effect of 90.0% in the group C were significantly higher than 74.19 +/- 12.12 and 76.7% in the group A and 72.29 +/- 11.52 and 73.3% in the group B (P<0.05)., Conclusion: The scalp acupuncture and rehabilitation therapy have synergistic action in improving motor function for the hemiplegic patient of cerebral thrombosis at convalescent period, and it is a better method for cerebral thrombosis at the convalescent stage.

Whereas iron chelators have been proposed as therapeutic agents in stroke, changes in free iron levels have never been explored after focal brain ischemia. Therefore, free and total iron levels in cortical tissue and free iron levels in plasma were measured before and after (1, 4 and 24h) photothrombotic occlusion of cortical vessels in rats. Brain ferritin expression and localization were also investigated before and after (24, 72 and 192 h) occlusion. The results showed that free iron remained below detectable levels in plasma and that the lesion exhibited high levels of free and total iron. As compared to contralateral values, free iron levels in ischemic core and penumbra increased (+50%) at 1h and returned to control values at 4h post-occlusion. In contrast, the increase in total iron levels (+20-30%) was long-lasting, but confined to the ischemic core. A time-dependent increase in the expression of both chains of ferritin was detected in regions that previously exhibited free iron accumulation. Finally, ischemic damage was reduced by the liposoluble iron chelator 2,2'-dipyridyl (20 mg/kg, i.p.) when injected 15 min or 1 h post-occlusion, yet not later (4 h). In conclusion, our results show that focal brain ischemia results in an early and transient elevation in free iron levels in the ischemic tissue and suggest that free iron excess does not originate in blood. They also highlight the importance of starting iron chelation therapy as soon as possible after stroke.

Background and Purpose: Results of our recent pilot clinical trial suggest that the efficacy of thrombolytic therapy in acute ischemic stroke may be enhanced by the coadministration of high-dose albumin. Here, we explored the microvascular hemodynamic effects of this combined therapy in a laboratory model of cortical arteriolar thrombosis., Methods: We studied the cortical microcirculation of physiologically monitored rats in vivo by two-photon laser-scanning microscopy after plasma-labeling with fluorescein-dextran. We induced focal thrombosis in 30- to 50-microm cortical arterioles by laser irradiation and measured arteriolar flow velocity by repeated line-scanning. At 30 minutes post-thrombosis, we treated animals with the thrombolytic agent, reteplase, which was coadministered with either human albumin, 2 g/kg, or with saline control., Results: Baseline arteriolar flow velocity averaged 3.8+/-0.7 mm/s, was immediately reduced by thrombosis to 22% to 25% of control values, and remained unchanged before treatment. Subthrombolytic doses of reteplase combined with saline led to a median increase in flow velocity to 37% of control distal to the thrombus (P=nonsignificant versus pretreatment). By contrast, reteplase combined with albumin therapy resulted in a prompt, highly significant increase of median flow velocity to 58% of control levels (P=0.013 versus reteplase+saline), which remained significantly higher than the reteplase+saline group at multiple time-points over the subsequent hour., Conclusions: The beneficial effect of subthrombolytic doses of reteplase on microvascular hemodynamics distal to a cortical arteriolar thrombosis is markedly enhanced by the coadministration of high-dose albumin therapy; these results have important clinical implications for the management of patients with acute ischemic stroke.

Antiphospholipid syndrome (APS) is identified as the presence of antiphospholipid antibodies (aPLs) in patients with vascular thrombosis and/or pregnancy morbidity (including fetal death, premature birth and habitual abortion). Neurological manifestations in patients with APS are common, whereas movement disorders are rarely seen. We report an extremely rare case of APS presented with parkinsonism and review the literature to address the clinical profile and possible pathophysiologic mechanism of this disorder.

Introduction: Although the prognosis of cerebral venous thrombosis (CVT) is better than previously reported, long-term behavioral and cognitive sequelae have not been systematically investigated., Objective: The aim of this study was to evaluate the long-term functional and cognitive outcome in CVT patients., Methods: We included all patients admitted to the Neurology department of the Amiens university hospital between January 1997 and December 2002 with the diagnosis of CVT. Outcome between April and June 2003 was evaluated. Patients with cognitive complaints or impaired, MMSE were assessed using a standardized neuropsychological battery and behavioral disorder assessment., Results: Among the 26 patients fulfilling inclusion criteria, 16agreed to participate and formed the study population (13 women; median age: 46.8years). The median follow-up was 34.5months. Functional ability assessed using the modified Rankin Scale (mRk) was relatively spared (mRk=0; n=6; mRk=1; n=6; mRk=2; n=4). Ten patients with cognitive complaints underwent a detailed neuropsychological assessment: it revealed deficits of long-term memory and executive functions., Conclusions: Despite relatively good functional long-term outcome, our results indicate that CVT patients suffer from long-term memory deficit and moderate executive dysfunction. Such a pattern is close to that observed in arterial stroke although less severe and this warrants a larger study.

We report a patient with cerebral venous thrombosis who presented with acute onset of severe prolonged vertigo, nausea, vomiting, unilateral decreased caloric response and occipital headache, simultaneously with acute venous cerebral infarcts on brain MRI. Although the patient had occipital headache, overall symptoms and signs closely mimicked those of acute unilateral vestibulopathy. Cerebral venous thrombosis should be considered in the differential diagnosis of acute unilateral vestibular syndrome.

We report 2 patients with angiographically demonstrated basilar artery thrombosis who received emergent intra-arterial thrombolysis with successful recanalization of the basilar artery. In the ensuing weeks after the procedure, both patients were in a locked-in state and had sustained large bilateral regions of pontine ischemia on brain imaging. Following aggressive supportive care and rehabilitation, outcomes obtained prospectively revealed that both patients made a remarkable recovery, becoming fully independent with Barthel scores of 20 and modified Rankin scores of 2.

Cerebral venous thrombosis is currently thought to be a relatively rare and benign entity in childhood. Recent studies however have shown that cerebral venous thrombosis is more common than previously believed, and carries significant mortality and neurologic morbidity. Neonates are the most commonly affected age group, compared to children >1 month of age. Magnetic resonance imaging venography is the gold standard by which this diagnosis should be made. Clinical trials are currently necessary to determine the most efficacious,safe, and age-specific approach for anticoagulation for this childhood disorder.

In recent reports, cerebral vein and sinus thrombosis has had a better long-term prognosis than previously thought. However, there may be long-term problems that have not attracted enough attention. The aim of this chapter is to examine the literature for studies reporting long-term prognosis and outcome after cerebral vein and sinus thrombosis. The long-term prognosis after cerebral vein and sinus thrombosis mainly depends on underlying diseases, e.g. cancer. If no serious underlying disease is present, the long-term prognosis is generally good. However, death, impaired functional outcome, headache, epileptic seizures, cognitive impairment and recurrent thrombosis occur in some patients. Although the general long-term prognosis after cerebral vein and sinus thrombosis is good, the practicing clinician handling these patients should be aware of certain complications that are not uncommon. Follow-up of these patients is important, even if they initially seem to have recovered completely.

Background and Purpose: High-dose human albumin is robustly neuroprotective in preclinical ischemia models and is currently in phase III clinical trial for acute ischemic stroke. To explore the hypothesis that albumin's protective effect is mediated in part by salutary intravascular mechanisms, we assessed microvascular hemodynamics in a model of laser-induced cortical arteriolar thrombosis., Methods: The cortical microcirculation of anesthetized, physiologically monitored Sprague-Dawley rats was studied in vivo via a frontoparietal cranial window (intact dura) by two-photon laser-scanning microscopy after plasma-labeling with fluorescein-dextran. Focal thrombosis was produced in 30- to 50-mum cortical arterioles by laser irradiation. Arteriolar flow velocity was measured repeatedly by line-scanning. At 30 minutes post-thrombosis, animals were treated with either human albumin, 2 g/kg, or with saline control., Results: Baseline arteriolar flow velocity averaged 3.5+/-1.8 mm/s and was reduced to 10% to 13% of control values by laser-induced thrombosis, which also led to focal vasodilatation (mean, 49% above baseline diameter). Saline treatment at 30 minutes post-thrombosis failed to influence arteriolar flow velocity, which remained depressed at 10% to 22% of control throughout the subsequent 60- to 90-minute observation period. By contrast, albumin treatment induced a prompt rise in median flow velocity to 38% of control by 10 minutes post-treatment, and to 61% to 67% of control by 50 to 60 minutes., Conclusions: High-dose albumin therapy induces a prompt, sustained improvement in microvascular hemodynamics distal to a cortical arteriolar thrombosis; these data support an important intravascular component to albumin's protective effect in acute cerebral ischemia.

Background: We aimed to identify the rate of major neurologic improvement (MNI) at 24 h following endovascular recanalization therapy (ERT) for acute ischemic stroke and its association with short-term outcome., Methods: We retrospectively reviewed consecutive acute ischemic stroke patients presenting to our institution over 4 years and undergoing ERT. Angiograms were independently reviewed. Data on demographics, medical history, initial NIHSS score, 24-hour NIHSS score, site of acute vascular lesion, pre- and posttreatment Thrombolysis in Myocardial Infarction scores, symptomatic intracerebral hemorrhage (within 36 h of intervention that was associated with a 4-point decline in NIHSS score) and discharge disposition were collected. We used logistic regression analysis to identify predictors of MNI (defined as >or=8-point improvement in NIHSS or a score of 0-1 at 24 h) and favorable discharge status (defined as home or acute rehabilitation)., Results: Sixty-eight patients were included (median age = 71 years, 60% women, median NIHSS score = 19.5, anterior circulation = 75%). The modes of ERT were pharmacologic only (28%), mechanical only (35%) and multimodal therapy (37%). Thrombolysis in Myocardial Infarction 2 or 3 recanalization was achieved in 64.7% (mechanical only 46%, pharmacologic only 63% and multimodal 84%). The outcomes were: symptomatic intracerebral hemorrhage (11.8%), MNI (26.5%) and favorable discharge (41.2%). Age (OR = 0.93, p = 0.003) and cardioembolic stroke subtype (OR = 6.0, p = 0.018) were independent predictors of MNI. MNI was a strong predictor of favorable discharge status (OR = 46.4, p < 0.001)., Conclusions: Despite initial stroke severity, MNI occurred in over one fourth of the patients and independently and strongly predicted favorable discharge outcome., ((c) 2008 S. Karger AG, Basel.)

Intracranial venous thrombosis may occur at any time from infancy to old age and its clinical expression varies widely and sometimes it may present without focal signs. The most common symptoms are: headache, vomiting, transient or persistent visual obscuration, focal or generalized seizures, lethargy and coma, while papilledema is a common sign. There may also be alternating focal deficits, hemiparesis or paraparesis, or other focal neurological deficits depending on the location of the venous structures involved. Symptom onset is either acute, subacute or chronic. Even with a severe initial presentation, partial or complete recovery is possible, underlying the importance of early recognition. Antithrombotic treatment must be administered at diagnosis as soon as possible.

Introduction: Microvasculature and associated pathologies mandate dynamic imaging. We evaluated a novel miniaturized confocal laser scanning probe for in vivo visualization of blood vessels, blood flow, cell tracking and perfusion in both healthy rodents and disease models., Methods: The hand-held confocal microscopy system allowed a 500- to 2,400-fold magnification at a dynamically variable imaging depth. Different intravital stains were used alone or in combination for tissue, nuclear, plasma and vascular endothelial cell staining and for blood flow visualization, and targeted staining for individual cell populations., Results: Precision optical sectioning yielded high-resolution images in vivo. Leucocyte-endothelium interactions in brain microvasculature were followed in serial sections. A microthrombosis was identified after sequential injection of FITC-labelled erythrocytes, FITC-dextran and acriflavine. Glomerular alterations were visualized in the MRL/lprmouse model of lupus nephritis., Discussion: Intravital confocal microscopy with a miniaturized hand-held probe combines high-resolution subsurface imaging in real time for dynamic visualization of vessels, cells, blood flow and associated pathologies, permitting a truly comprehensive vascular imaging in vivo at the cellular level., (Copyright 2008 S. Karger AG, Basel.)