Large Cerebral Vessels Research Articles

Abstract T MP18: Physical Activity Prior to Stroke May Exert Neurorestorative Effects by Increasing Vascular Endothelial Growth Factor Expression after Acute Ischemic Stroke

Objective: Previous studies by our group have found an independent association between pre-stroke physical activity (PhA) and good functional outcome in a cohort of patients with a cerebral large vessel occlusion. In this study our aim was to evaluate the possible molecular mechanisms by which PhA exerts its neurorestorative effect by studying angiogenic and neurogenic growth factors at different timepoints after stroke onset. Methods: We included 159 consecutive previously independent patients with an acute stroke due to MCA or TICA occlusion within the first 8 hours from stroke onset. Pre-stroke PhA was evaluated with the international physical activity questionnaire (IPAQ) and subjects were classified into 2 groups: low and high level of pre-stroke PhA. We measured serum levels of Vascular Endothelial Grow Factor (VEGF), Granulocyte Colony-Stimulating Factor (G-CSF) and Brain-Derived Neurotrophic Factor (BDNF) at admission, day 7, and 3 months. We considered good functional outcome at 3 months (mRS ≤ 2) as primary endpoint. Results: Mean age was 68 and median NIHSS 17. Serum levels of VEGF, G-CSF and BDNF at admission were similar among patients with good (46.5%) and poor (53.5%) functional outcome, However, VEGF and G-CSF serum levels were significantly higher at 7 days and 3 months (p<0.05) in those patients who showed good functional outcome, emerging as independent predictors of good outcome in adjusted logistic regression analyses. When we studied the temporal profile of biomarkers in the different groups of pre-stroke PhA, we observed that those more physically active before stroke had a significantly higher increment of VEGF at day 7 compared to those with low PhA level. In a logistic regression model adjusted for age, sex, baseline NIHSS, reperfusion therapies administered, VEGF increment at day 7 and level of PhA previous to stroke, both VEGF increment and high level of pre-stroke PhA emerged as independent predictors of good functional outcome with and OR 7.7 and 33 respectively, p<0.05. Conclusion: Beneficial effect of pre-stroke PhA in stroke outcomes may be mediated by increasing the expression of VEGF in the first days after stroke, triggering angiogenesis processes.

Abstract T MP1: Predictive Factors of Favorable Outcome in Patients With Acute Large Vessel Occlusion

Background: The data of the nationwide prospective registry of acute cerebral large vessel occlusion (RESCUE-Japan Registry) was analyzed to know the predictive factors of favorable outcome at 90 days Methods: In this registry, patients with acute cerebral large vessel occlusion admitted within 24 h after onset were prospectively registered. The effect of various factors including endovascular treatment (EVT), intravenous tissue plasminogen activator (IV-tPA), and other medication on favorable outcome (modified Rankin scale 0-2) was analyzed. Results: A total of 1,315 patients were analyzed. The number of patients in favorable outcome was 422 (32.1%). Logistic regression analysis revealed that higher NIHSS (OR 0.875, 95%CI 0.858-0.894) and advanced age (OR 0.963, 95% CI 0.952-0.975) were significantly related to unfavorable outcome (Fig. 1). In contrast, IV-tPA (OR 2.489, 95% CI 1.867-3.319), EVT (OR 1.375, 95% CI 1.013-1.865), and free radical scavenger, edaravon, (OR 1.483, 95% CI 1.027-2.143) were significantly associated with favorable outcome. Combination with IV-tPA or EVT with free radical scavenger was better than without it (Fig. 2). Conclusions: This analysis indicated that IV-tPA, EVT and free radical scavenger were effective to obtain favorable outcome in the patients with acute large vessel occlusion. Combination with free radical scavenger was also effective.

Efficacy of Endovascular Treatment for Acute Cerebral Large-Vessel Occlusion: Analysis of Nationwide Prospective Registry

The aim of this nationwide, prospective registry of acute cerebral large-vessel occlusion was to assess the efficacy of endovascular treatment (EVT) on outcome in the "real-world" settings. Medical information of the patients was anonymized and registered prospectively through a Web site from 84 medical centers in Japan. Reperfusion of the affected arteries was evaluated by the Thrombolysis in Cerebral Infarction grade on cerebral angiography or by the modified Mori grade on magnetic resonance angiography. Clinical outcome was evaluated by modified Rankin Scale (mRS) at 90days after onset. Symptomatic intracranial hemorrhage and procedure-related complications were also analyzed. Among intravenous tissue plasminogen activator (IV t-PA)-failed patients, no significant difference in favorable outcome was seen with or without EVT overall (41.7% versus 36.8%, P=.55). However, EVT significantly increased favorable outcomes (mRS score 0-2) in patients with internal carotid artery (ICA)/middle cerebral artery M1/basilar artery (BA) occlusion (41.3% versus 20.5%, P=.019). In contrast, among t-PA-ineligible patients, EVT significantly increased favorable outcomes overall (29.1% versus 19.5%; odds ratio, 1.70; P=.007). Furthermore, favorable outcomes were more common in patients with ICA/M1/BA occlusion (29.0% versus 10.3%; odds ratio, 3.56; P<.0001). Multivariate analysis also confirmed the efficacy of IV t-PA, EVT, and their combination for favorable outcome. EVT significantly improved clinical outcomes in IV t-PA-failed and t-PA-ineligible patients with ICA/M1/BA occlusion. These findings support the introduction of EVT for acute proximal artery occlusion.

Hypertension, Brain Damage and Cognitive Decline

Loss of cognitive function is one the most devastating manifestations of ageing and vascular disease. Cognitive decline is rapidly becoming an important cause of disability worldwide and contributes significantly to increased mortality. There is growing evidence that hypertension is the most important modifiable vascular risk factor for development and progression of both cognitive decline and dementia. High blood pressure contributes to cerebral small and large vessel disease resulting in brain damage and dementia. A decline in cerebrovascular reserve capacity and emerging degenerative vascular wall changes underlie complete and incomplete brain infarcts, haemorrhages and white matter hyperintensities. This review discusses the complexity of factors linking hypertension to brain functional and structural changes, and to cognitive decline and dementia. The evidence for possible clinical markers useful for prevention of decreased cognitive ability, as well as recent data on vascular mechanism in the pathogenesis of cognitive decline, and the role of antihypertensive therapies in long-term prevention of late-life cognitive decline will be reviewed.

Abstract TMP82: Increased Intracerebral Hemorrhage During Acute and Chronic Hypertension in Alzheimer's Transgenic Mice

Hypertension is a major risk factor for intracerebral hemorrhage (ICH), and the accumulation of amyloid-beta (Aβ) in the cerebrovascular system, cerebral amyloid angiopathy (CAA), is also a significant risk factor for intracerebral hemorrhage ICH. Currently, there are no animal studies demonstrating a direct involvement of hypertension in the accumulation of Alzheimer’s disease-like pathology. To address this issue we have developed several mouse models that combine hypertension protocols with amyloid precursor protein (APP) transgenic mice (Tg2576), which accumulate significant CAA in the large cerebral vessels and the meninges by 18 months of age. The goal of this study was to determine the effect of acute and chronic hypertension on ICH in wildtype and a transgenic mouse model overexpressing a mutant human amyloid precursor protein (Tg2576 mice) associated with early onset AD and CAA. Fifteen-month-old Tg2576 mice and non-transgenic (nTg) littermates were treated with an angiotensin II (AngII) infusion (1000 ng/kg/min) and L-NAME (100 mg/kg/day) in drinking water to produce chronic hypertension. One week later, transient acute hypertension was induced by daily AngII injections (0.5 μg/g, s.c., twice daily) to produce ICH. A similar increase in mean blood pressure was observed in Tg2576 and nTg mice when evaluated 2 weeks after initiation of treatment. However Tg2576 mice had a higher incidence of signs of stroke compared with nTg littermates (P &gt; 0.05). These data suggest that the accumulation of Aβ in the brain has an important role in development of ICH. Moreover, there was robust glial activation and increase in CAA in the gray matter of Tg2576 mice showing that hypertension may affect gray as well as white matter in the brain. Further studies may provide insights into the hypertension-induced changes in the cerebral vascular system that initiated the increase in CAA. The accumulation of Aβ in the cerebrovascular system is a significant risk factor for intracerebral hemorrhage (ICH), and has been linked to endothelial transport failure and blockage of perivascular drainage. While management of hypertension and atherosclerosis can reduce the incidence of ICH, there are currently no approved therapies for attenuating CAA.

Mechanical revascularization of acute iatrogenic anterior cerebral artery occlusions: use of a new coaxial dual-lumen balloon catheter results in rapid access and flow restoration

Acute iatrogenic occlusion of cerebral vessels is a risk during the performance of neuroendovascular procedures. Most commonly this is a result of thrombus formation within the vessel, thromboembolism or an...

Acute encephalopathy as the initial manifestation of CADASIL

A 29-year-old right-handed G1P1 Caucasian woman presented with acute bifrontal headache (which resolved within 1 day), confusion, and difficulty using her right hand on postpartum day 10. She did not report nausea, vomiting, or visual complaints. The patient was previously healthy except for her recent preeclampsia, which required emergent cesarean section. On examination, the patient was afebrile, awake, alert, and apathetic. She was able to follow few one-step midline commands (e.g., eye opening and closing) inconsistently but not appendicular commands. Her neurologic deficits were remarkable for expressive aphasia, intermittent receptive aphasia, and hyperreflexia with bilateral extensor plantar responses. No meningismus or other focal neurologic deficits were present. Routine laboratory testing including urine toxicology screen was normal. C-reactive protein was 23 mg/L (reference range: <5 mg/L), and erythrocyte sedimentation rate (ESR) was 38 mm/h (reference range: 0-20 mm/h). Rheumatologic panel was negative. Brain MRI showed extensive non-contrast-enhancing T2/fluid-attenuated inversion recovery hyperintensities involving periventricular and deep white matter, especially the centrum semiovale, corpus callosum, bilateral anterior temporal lobes, bilateral caudate nucleus, and globus pallidus (figure, A-C). No evidence of acute or previous stroke was found. CT angiogram and venogram revealed no cerebral sinus thrombosis or large vessel vasculitis. Lumbar puncture opening pressure was 18.5 cm H2O. CSF showed normal cell counts, protein, and glucose levels without oligoclonal bands. EEG recorded in awake, drowsy, and sleep state was normal. Dilated ophthalmic examination showed no microangiopathy or retinal branch arterial occlusion. Audiologic examination was normal.

Extensive Coagulation Profile in Children with Sickle Cell Disease and Its Role in Cerebral Micro-Vasculopathy

AbstractAbstract 3247Activation of the coagulation system is present in adults with Sickle Cell Disease (SCD) who display higher levels of thrombin-antithrombin complex (TAT), prothrombin fragment F1+2, D-dimer, tissue factor and platelet activity. Whether the activation of the coagulation system is a bystander phenomenon or a main determinant of clinical complications is under investigation. Although thrombotic complications in SCD arise since infancy, the coagulation system in children has been poorly explored. We performed a comprehensive and systematic evaluation of the coagulation system in children with SCD and investigated its possible role in the development of the main clinical manifestations of SCD in childhood.The following markers of hemostatic and endothelial function were evaluated during steady state: factor VIII activity (FVIII), von Willebrand factor antigen (vWF:Ag) and collagen binding activity (vWF:CBA), PAI-1 antigen (PAI-1:Ag), t-PA antigen (t-PA:Ag), D-dimer, P-selectin, Nitric Oxide (NO), F1+2, TAT, ADAMTS-13 antigen (ADAMTS-13:Ag) and activity (ADAMTS-13:act). Markers of hemolysis (hemoglobin, reticulocytes, aptoglobin, bilirubin, LDH), inflammation (white blood cells, neutrophils, C reactive protein) were measured. Children were not in chronic transfusion.Magnetic Resonance (MRI), Angio Magnetic Resonance (MRA), Transcranial Doppler (TCD), Tricuspid Regurgitant Velocity (TRV) data and frequency of clinical complications were correlated with coagulation parameters. Continuous variables were compared using two-sided Student's t-test and Mann-Whitney non-parametric test, categorical variables using Chi-square and Fisher's exact test. Correlations between variables were evaluated by the Pearson or Spearman coefficient.Thirty-five HbS/HbS- 3 HbS/betathalassemia° (20 M and 18 F, mean age 6.49 years), and 6 HbS/HbC patients (3 M and 3 F, mean age 11.2 years) were evaluated. 60% of HbS/HbS and HbS/betathalassemia° children presented higher level of FVIII, D-dimer, F1+2 and lower level of NO, revealing coagulation activation since early age in HbS/HbS and HbS/betathalassemia° but not in HbS/HbC (Table 1). Coagulation variables correlated positively with markers of inflammation, hemolysis, endothelial activation demonstrating a broad involvement of the coagulation system in these processes, while correlated negatively with HbF (Table 2). No correlation was seen between coagulation variables and cerebral large vessel vasculopathy investigated by TCD and MRA nor TRV (p >0.05). Patients with Silent Infarcts on MRI (n.9) showed significant decrease in t-PA (4.53 vs 7.67, p 0.03) and ADAMTS-13 Ag (1.15 vs 1.50, p 0.05) -suggesting the presence of endothelial dysfunction- and a tendency toward higher D-dimer (2879.01 vs 1569.51), F1+2 (319 vs 231), TAT (17.17 vs 10.46) -suggesting a trend towards enhanced clotting activation compared to patients without Silent infarcts (n.21). Increase in D-dimer was associated with a Relative risk of 6 (p <0.05) to develop Silent Infarcts. No correlation was found between coagulation activation and Acute Chest Syndrome or Vaso-occlusive crisis.Table 1Coagulation profile in HbS/HbS-HbS/Betathalassemia° and HbS/HbC patientsHbS/HbS+HbS/Betathalassemia°HbS/HbCpVariableMeanFVIII:C %184.96119.220.003VWF:Ag %150.05100.630.013VWF:CBA %135.38107.360.124PAI:Ag ng/ml8.736.850.833t-PA ng/ml6.914.520.062D-dimer ng/ml1906.39366.480.000NO μmol/L7.188.70.336P-selectin ng/ml47.7629.700.010F1+2 pmol/l254.26118.500.037TAT ng/ml12.345.140.359ADAMTS-13:Ag μg/ml1.371.460.653ADAMTS-13:act %79.4278.940.801ADAMTS-13:act/VWF:Ag0.520.780.003Table 2Correlations between hematologic and coagulation parameters in HbS/HbS- HbS/Betathalassemia° (first value is Pearson or Spearman coefficient, second is p-value)White Blood CellsNeutrophilsPlateletsFetal HemoglobinReticulocytesLDHFVIII:C−0.3740.021VWF:Ag−0.3220.049VWF:CBA0.3680.023PAI:Ag0.4490.3690.3330.3520.0050.0250.0440.033t-PA0.3440.034D-dimer0.5590.438−0.3930.3890.4210.0010.0110.0210.0230.013P-selectin0.4610.4000.520−0.4130.3810.0040.0160.0010.0110.020F1+20.4000.5120.3370.0160.0010.044TAT0.3970.3810.3760.0170.0220.024ADAMTS-13 Ag0.4710.004 Disclosures:No relevant conflicts of interest to declare.

Update on acute endovascular and surgical stroke treatment

Emergency stroke care has become a natural part of the emerging discipline of neurocritical care and demands close cooperation between the neurologist and neurointerventionists, neurosurgeons, and anesthesiologists. Endovascular treatment (EVT), including intra-arterial thrombolysis, mechanical thrombectomy and angioplasty/stenting, is under rapid development. Although EVT has yet to be shown in randomized controlled trials to improve clinical outcome compared to intravenous thrombolysis, it is far better in achieving recanalization of occluded large cerebral vessels, which is crucial for rescuing the penumbra. Moreover, decompressive craniectomy is now a well-established treatment option for malignant middle cerebral artery infarction and cerebellar stroke. Using a case-based approach, this article reviews recent achievements in advanced treatment options for patients with acute ischemic stroke.

E-018 Initial experience with distal guide catheter placement in the treatment of cerebrovascular disease: clinical safety and efficacy

BackgroundThe treatment of cerebrovascular diseases continues to grow with improvements in technology. The use of stable guide catheters in the large cervical cerebral vessels has historically been paramount to the...

Acute stroke treatment using the Penumbra endovascular mechanical thrombolysis device: a single-centre experience

Ischaemic stroke due to occlusion of large cerebral vessels has a poor prognosis. The clinical outcome is related to efficacy and timing of recanalisation of the occluded arteries. We report our experience with a thrombus aspiration device (Penumbra), and focus on pre- and postprocedural management. We retrospectively reviewed 18 consecutive patients with acute ischaemic stroke due to the occlusion of large cerebral vessels who were treated with mechanical thrombolysis at our centre between September 2009 and July 2010. Preprocedural symptoms were quantified using the National Institutes of Health Stroke Scale (NIHSS). Mechanical thrombolysis was performed with the Penumbra system. Intravenous thrombolysis was done only if <3 h had elapsed since symptom onset. Associated vessel stenoses were treated with stenting. All patients underwent neurological examination and postprocedural magnetic resonance angiography (MRA) at 3 and 6 months. Mechanical thrombolysis using the Penumbra system was performed in all cases. A total of 83% of treated vessels had a value of 2/3 according to the Thrombolysis in Cerebral Infarction (TICI) scale. In seven patients (39%) intravenous thrombolysis was unsuccessful, and salvage mechanical thrombolysis followed. Three patients died after the procedure (16.7%). Five patients (27.8%) required a stenting procedure. All patients reported a significant improvement in symptoms (mean baseline NIHSS 19.6±5.6; mean postprocedural NIHSS, 7.8±5.5 p<0.0001) Our preliminary experience with the Penumbra mechanical thrombolysis system confirms previously reported results showing the efficacy and safety of the device in treating acute stroke caused by the occlusion of large intracranial vessels.

Migraine with Prolonged Aura Versus Migrainous Infarction: Multimodality Imaging in a Unique Case (P03.213)

Objective: To report a patient with very prolonged migrainous visual aura and to discuss the significance of multimodality imaging in this clinical setting. Background The International Headache Society9s (IHS) definition of migraine with prolonged aura indicates that at least one aura symptom should persist between 60 minutes and 7 days. Migrainous infarction is an attack of migraine during which at least one aura symptom is not fully reversible within 7 days or absence of neuroimaging evidence of corresponding ischemia. A rigid time frame separating these two entities may be artificial. There is limited experience and knowledge in utilizing magnetic resonance perfusion imaging (MRI-PI) and magnetoencephalography (MEG) in this clinical setting. Design/Methods: We describe a patient with unusually prolonged migrainous aura evaluated by the authors, on whom multimodality neuroimaging was completed. Results: A 54 year-old man presented with complaints of scintillations, photopsias, and visual loss in the left hemifield, along with right temporo-occipital headache, photophobia, nausea, and emesis. Neurologic examination confirmed a complete left homonymous hemianopsia. Brain MRI revealed no acute ischemic lesion and no large cerebral vessel occlusion on MRA. MRI-PI revealed slightly increased cerebral blood flow and blood volume in the medial right occipital lobe. EEG was unremarkable. During the resting state, MEG detected expected coherent activity in bilateral occipital cortices. Unexpectedly, maximal coherence was observed in the right medial temporal region. On left hemifield stimulation, there was no MEG activity in the right occipital cortex. Valproate resolved the headache within 4 days while Humphrey Visual Field Testing confirmed resolution of left homonymous hemianopsia after 7 weeks. Conclusions: Migrainous aura can last longer than 7 days. The distinction between prolonged migrainous aura and migrainous infarction should not rely only on a rigid time frame. Multimodality neuroimaging allows this distinction to be made with clarity. The IHS criteria may need to be revised. Disclosure: Dr. Ashraf has nothing to disclose. Dr. Bowyer has nothing to disclose. Dr. Mitsias has nothing to disclose.

Abstract 138: The Interim Results Of The Multicenter Prospective Registry Of Acute Cerebral Large Vessel Occlusion In Japan: The Impact Of Rescue Endovascular Treatment For Intravenous Tissue Plasminogen Activator-failed Patients

Background: The multicenter prospective registry of Japan (RESCUE-Japan Registry) was performed to clarify the clinical impact of endovascular treatment (EVT) on acute cerebral large vessel occlusion. Methods: Patients admitted within 24 h after stroke onsets were prospectively registered from July, 2010 to June, 2011. The efficacy of rescue EVT for intravenous intravenous tissue plasminogen activator (IV-tPA)-failed patients was analyzed. Results: Among a total of 1,385 patients registered in this study, 940 patients (520 women, 420 men) with 3 months outcome were investigated as the interim analysis. Mean age was 74.5 years (range 22-99 years). The mean arrival time was 237.4 min after onset, and mean NIHSS was 15.6 points. The first treatment within 3 hours was IV-tPA in 51%, conservative therapy in 33%, EVT in 16%. In the patients treated with IV-tPA (n=148), significant recanalization (TICI 2B, 3 or modified Mori’s grade 3) was obtained in approximately 40% in M1 distal and M2 of MCA, but less than 20% in ICA 1-3 hours after IV-tPA. Rescue EVT after IV-tPA was performed in 72/285 patients (25.3%), which was significantly increased the previous study in 2008. Rescue EVT contributed significant recanalized the affected arteries (TICI 2B-3: 17% to 68%) ( Fig .1) and increased the ratio of favorable outcome (modified Rankin scale:0-2) in ICA (0% vs 50%, p=0.037) ( Fig . 2), and M1 proximal occlusion (33% vs 83%, p=0.033) ( Fig .3). Conclusions: The interim analysis of this nationwide registry suggested the efficacy of rescue EVT in IV-tPA failed patients with occlusion of the ICA and M1 proximal portion.

Use of Near Infrared Transillumination / Back Scattering Sounding (NIR-T/BSS) to assess effects of elevated intracranial pressure on width of subarachnoid space and cerebrovascular pulsation in animals.

The objective was to assess changes in the width of the subarachnoid space (SAS) and amplitude of cerebrovascular pulsation (CVP) during acute elevation of intracranial pressure (ICP) using Near Infrared Transillumination/Back Scattering Sounding (NIR-T/BSS). Changes in the width of the SAS and amplitude of CVP were observed in rabbits during experimental ICP elevation induced by: (1) quick injections of saline into the subdural space of the spinal cord, and (2) distension of a surgical catheter balloon placed intracranially in the subdural space. The amplitude of CVP was also assessed during acute elevation of blood pressure in the intracranial portion of the internal carotid artery (ICA) induced by adrenaline. Each of the injections of saline caused a transient rise in the width of the SAS and amplitude of CVP. The amplitude of the increase in CVP was dependent on changes in blood pressure in the ICA (r=-0.82, P<0.01). Distension of the intracranial balloon resulted in elimination of the respiratory oscillations in the CVP and increased its systolic-diastolic amplitude. An increase in the amplitude of CVP was evoked by adrenaline without an increase in the carotid blood flow. We demonstrated that during elevation of ICP the amplitude of CVP depends on blood pressure rather than on blood flow in large cerebral vessels. Elimination of the respiratory oscillations by a minute ("sub-critical") ICP increase may be used as an early indicator of rising ICP. The direction of changes recorded using NIR-T/BSS was consistent with changes recorded using tensometric transducers.

Retrospective Nationwide Survey of Acute Stroke due to Large Vessel Occlusion in Japan: A Review of 1,963 Patients and the Impact of Endovascular Treatment

Background: The purpose of this study was to clarify the clinical impact of endovascular treatment (EVT) on acute cerebral large vessel occlusion using a nationwide survey of Japan conducted in 2009. Methods: Patients admitted within 24 h after stroke onset were registered retrospectively. Treatment selection, methods, and clinical results were analyzed. Results: A total of 1,963 patients (855 women, 1,108 men) treated in 2008 were registered from 68 medical centers in Japan. Mean age on admission was 74.1 ± 12.2 years (range 7–100 years). The first treatment was conservative therapy in 68%, intravenous tissue plasminogen activator (IV-tPA) in 21%, EVT in 9%, and combined IV-tPA + EVT in 2%. EVT mainly comprised angioplasty, intra-arterial thrombolysis and/or the combination of both. Patients treated ≤3 h after onset (1,286 cases) showed better clinical outcomes with combined IV-tPA + EVT than with conservative therapy, and significant differences in outcomes were seen for patients with occlusion of the basilar artery (p < 0.01) or middle cerebral artery (p < 0.01), but not the internal carotid artery. At >3 h after onset (677 patients), no IV-tPA was performed, and EVT was performed in 11%. Among the patients treated by EVT, there were significant differences in clinical outcome between complete recanalization (TIMI grade 3) and partial/no recanalization (TIMI grade 0–2) (p < 0.001; OR 5.98; 95% CI 3.27–10.96) and between any recanalization (TIMI grade 1–3) and no recanalization (TIMI grade 0) (p < 0.001; OR 36.15; 95% CI 4.88–267.53). Conclusions: This nationwide survey showed the efficacy of EVT with IV-tPA in patients with occlusion of the basilar or middle cerebral artery, but not of the internal carotid artery. The effects of new endovascular devices should be clarified in the near future.

Comment on: A Cost-Utility Analysis of Mechanical Thrombectomy as an Adjunct of Intravenous Tissue-Type Plasminogen Activator for Acute Large-Vessel Ischemic Stroke

Mechanical thrombectomy has become an emerging treat-ment option for patients with acute ischemic stroke due to cerebral large vessel occlusion. It is anticipated that reca-nalization rates as well as clinical outcomes are reduced in patients treated with intravenous (IV) tissue-type plasmino-gen activator (tPa) alone compared to those who were tre-ated with IV tPa (bridging therapy) and with endovascular intra-arterial (IA) therapy. To figure out whether costs, risks and utility of an additional interventional treatment in acute ischemic stroke are suitable to justify its use over IV tPa alone also in the dimension of procedural costs, Kim et al. developed a decision model based on currently available data.

Associations of Retinal Microvascular Signs and Intracranial Large Artery Disease

Intracranial large artery disease (ICLAD) is a major cause of ischemic stroke. Retinal microvascular changes are associated with stroke, including small vessel cerebral disease and extracranial carotid disease. We examined the relationship between ICLAD and retinal microvascular changes. This is a prospective cohort of 802 acute ischemic stroke patients. Retinal changes were assessed from photographs by graders masked to clinical data. ICLAD was evaluated using prespecified criteria. ICLAD was not associated with ipsilateral retinal arteriolar/venular caliber, focal arteriolar narrowing, or arteriovenous nicking. Severe enhanced arteriolar light reflex was independently associated with any ICLAD (P=0.006) and severe ICLAD (P<0.001). Enhanced arteriolar light reflex, but not retinal vessel caliber, was related to ICLAD. These data suggest that retinal microvascular signs have specific associations with large cerebral vessel disease.

Vascular Dementia

Cerebrovascular disease is the second leading cause of cognitive impairment in the elderly, either alone or in combination with Alzheimer's disease (AD). Vascular dementia (VaD) is heterogeneous in terms of both clinical phenotype and pathogenetic mechanisms. It may result from multiple cortical infarctions due to cerebral large vessel pathologies or to subcortical ischemic changes such as leukoaraiosis or lacunar infarction due to cerebral small artery disease. Clinical symptoms and signs vary depending on the location and size of the stroke lesion, and no single neuropsychological profile characteristic of VaD has been defined, although dysexecutive function is common. A slightly higher mortality rate and slower progression are reported in VaD compared with AD. VaD is potentially preventable by rigorous identification and treatment of cardiovascular disease risk factors, and modest symptomatic improvement with cholinesterase inhibitors has been reported.

Rapidly progressive primary central nervous system vasculitis

To describe a subset of cases in a large cohort of patients with primary CNS vasculitis (PCNSV) who appear to have a rapidly progressive clinical course. In the present study, we use our updated cohort of 131 consecutive patients with PCNSV seen over the 25-year period of 1983-2007 at Mayo Clinic, Rochester, MN, USA. The diagnosis of PCNSV was based on brain/spinal cord biopsy or cerebral angiography. The modified Rankin scale was used to identify rapidly progressive disease and included patients with Rankin scores indicating severe disability or death at diagnosis or within 6 months after the diagnosis. We compared patients with rapidly progressive disease to those without. Compared with the 120 patients without rapidly progressive vasculitis, the 11 patients with rapidly progressive vasculitis more frequently had paraparesis/quadriparesis at presentation, angiographic presence of bilateral, large-vessel vasculitis and MRI evidence of cerebral infarctions; those infarctions were more frequently multiple and bilateral, and more frequently involved both the cortex and subcortical regions on initial MRI. Granulomatous and/or necrotizing histopathological patterns of vasculitis were observed in patients with positive biopsies. Rapidly progressive PCNSV appears to form a subset of PCNSV at the worst end of the clinical spectrum of this vasculitis, characterized by bilateral, multiple, large cerebral vessel lesions and multiple CNS infarctions.

Inhibition of trigeminovascular dural nociceptive afferents by Ca 2+-activated K + (MaxiK/BK Ca) channel opening

Migraine is an episodic brain disorder with a significant morbidity. It is thought that activation of trigeminal afferents innervating the dura mater and large cerebral blood vessels is involved in the expression of the disorder. The selective large conductance calcium-activated potassium channels, the BK Ca or MaxiK channels, are intrinsic membrane proteins that are widely distributed in the brain. These channels are thought to be involved in controlling neuronal excitability and perhaps transmitter release, possibly in the trigeminocervical complex. We sought to investigate the role of MaxiK/BK Ca channels opening in several models of trigeminovascular nociception using NS1619, a benzimidazolone analogue. Intravenously administered NS1619 (10 mg kg −1) was able to inhibit neurogenic dural vasodilation ( F 4,20 = 19.23, P < 0.05, n = 6). NS1619 (intravenous) was not able to inhibit Aδ-fiber ( F 3.01,18.06 = 0.79, P = 0.52) or C-fiber ( F 3.14,18.84 = 0.76, P = 0.54) afferents in the trigeminal nucleus caudalis and C 1 region of the dorsal horn after dural electrical stimulation, but it was able to inhibit Aδ-fiber afferents after iontophoretic application of NS1619 ( t 5 = 3.23, P < 0.05, n = 6) after 5 min. Iontophoresed NS1619 was also able to inhibit l-glutamate induced firing in the trigeminocervical complex, in a dose-dependent manner ( F 3,54 = 3.06, P < 0.05). The data taken together indicate that the MaxiK/BK Ca channel may represent a novel therapeutic target in migraine.