Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients.

INTRODUCTION: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. PATIENTS AND METHODS: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. RESULTS: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = -0.47, P < .001 for 3-month modified Rankin Scale; rho = -0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. CONCLUSIONS: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

24-Hour Alberta Stroke Program Early CT Score Assessment in Post-Stroke Spasticity Development in Patients with a First Documented Anterior Circulation Ischemic Stroke.

BACKGROUND: Neuroanatomic substrates responsible for development of post-stroke spasticity are still poorly understood. The study is focused on identification of brain regions within the territory of the middle cerebral artery associated with spasticity development. METHODS: This is a single-center prospective cohort study of first documented anterior circulation ischemic strokes with a neurologic deficit lasting >7 days (from March 2014 to September 2016, all patients are involved in a registry). Ischemic cerebral lesions within the territory of middle cerebral artery were evaluated using the Alberta Stroke Program Early CT Score (ASPECTS) on control 24-hour computed tomography or magnetic resonance imaging. Spasticity was assessed with modified Ashworth scale. RESULTS: Seventy-six patients (mean age 72 years, 45% females; 30% treated with IV tissue plasminogen activator, 6.5% mechanical thrombectomy) fulfilled the study inclusion criteria. Forty-nine (64%) developed early elbow or wrist flexor spasticity defined as modified Ashworth scale >1 (at day 7-10), in 44 (58%) the spasticity remained present at 6 months. There were no differences between the patients who developed spasticity and those who did not when comparing admission stroke severity (National Institutes of Health Stroke Scale 5 [interquartile range {IQR} 4-8] versus 6 [IQR 4-10]) and vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, coronary artery disease). Nor was there a difference in 24-hour ASPECTS score (9 [IQR 8-10] versus 9 [IQR 7-10]). No differences were found between the groups with and without the early upper limb flexor spasticity of particular regions (M1, M2, M3, M4, M5, M6, lentiform, insula, caudate, internal capsule) and precentral-postcentral gyrus, premotor cortex, supplementary motor area, posterior limb of internal capsule, and thalamus were compared. CONCLUSIONS: We did not find any middle cerebral artery territory associated with post-stroke spasticity development by detailed evaluation of ASPECTS.

Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion.

Hyperacute changes in cerebral blood flow during cerebral ischaemia and reperfusion are important determinants of injury. Cerebral blood flow is regulated by neurovascular coupling, and disruption of neurovascular coupling contributes to brain plasticity and repair problems. However, it is unknown how neurovascular coupling is affected hyperacutely during cerebral ischaemia and reperfusion. We have developed a remote middle cerebral artery occlusion model in the rat, which enables multi-modal assessment of neurovascular coupling immediately prior to, during and immediately following reperfusion. Male Wistar rats were subjected to remote middle cerebral artery occlusion, where a long filament was advanced intraluminally through a guide cannula in the common carotid artery. Transcallosal stimulation evoked increases in blood flow, tissue oxygenation and neuronal activity, which were diminished by middle cerebral artery occlusion and partially restored during reperfusion. These evoked responses were not affected by administration of the thrombolytic alteplase at clinically used doses. Evoked cerebral blood flow responses were fully restored at 24 h post-middle cerebral artery occlusion indicating that neurovascular dysfunction was not sustained. These data show for the first time that the rat remote middle cerebral artery occlusion model coupled with transcallosal stimulation provides a novel method for continuous assessment of hyperacute neurovascular coupling changes during ischaemia and reperfusion, and offers unique insight into hyperacute ischaemic pathophysiology.

Assessment of cerebrovascular reserve in unilateral middle cerebral artery stenosis using perfusion CT and CO2 inhalation tests.

Purpose/Aim of the study: Cerebrovascular reactivity (CVR) is an important marker for assessing cerebrovascular disease. This study assessed the CVR by perfusion computed tomography (CT) and CO2 inhalation tests in patients with unilateral middle cerebral artery (MCA) stenosis disease. MATERIALS AND METHODS: Thirty-one patients with unilateral MCA stenosis disease diagnosed by digital subtraction angiography were studied. Patients were divided into two groups according to the degree of stenosis: severe and moderate. The regional cerebral blood flow (CBF) before and after CO2 inhalation was determined by perfusion CT. Regional CVR values were obtained by the following formula: increase (%) = (post-CBF) - (pre-CBF)/(pre-CBF) × 100%. RESULTS: No significant differences in the mean CBF in the MCA stenosis region were found between the affected and contralateral sides before the CO2 inhalation test; after the test, CBF was more significantly decreased on the affected side than on the contralateral side. The changes in CBF on the affected side were categorized into three types: increased CBF (17 cases), decreased CBF (12 cases) and no change in CBF (2 cases). The rate of CVR impairment among severe stenosis patients (13/19) was higher than that among moderate stenosis patients (3/12). CVR was significantly correlated with the degree of stenosis (r = 0.423, P = 0.018). CONCLUSION: CVR impairment was found in approximately half of patients with unilateral MCA stenosis. Along with an increase in the degree of stenosis, patients with unilateral MCA stenosis were more likely to exhibit CVR impairment. It is important to assess the CVR in patients with unilateral MCA stenosis, especially those with severe stenosis.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats.

OBJECTIVE: The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND METHODS: Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. RESULTS: Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min(-1) vs. 0.07 ± 0.02 min(-1), p = 0.661 for K(trans); 0.30 ± 0.05 min(-1) vs. 0.37 ± 0.11 min(-1), p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). CONCLUSION: Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

Assessment of Collateral Status by Dynamic CT Angiography in Acute MCA Stroke: Timing of Acquisition and Relationship with Final Infarct Volume.

BACKGROUND AND PURPOSE: Dynamic CTA is a promising technique for visualization of collateral filling in patients with acute ischemic stroke. Our aim was to describe collateral filling with dynamic CTA and assess the relationship with infarct volume at follow-up. MATERIALS AND METHODS: We selected patients with acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT, single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after stroke onset. For each patient, a detailed assessment of the extent and velocity of arterial filling was obtained. Poor radiologic outcome was defined as an infarct volume of ≥70 mL. The association between collateral score and follow-up infarct volume was analyzed with Poisson regression. RESULTS: Sixty-one patients with a mean age of 67 years were included. For all patients combined, the interval that contained the peak of arterial filling in both hemispheres was between 11 and 21 seconds after ICA contrast entry. Poor collateral status as assessed with dynamic CTA was more strongly associated with infarct volume of ≥70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus-slow collaterals) were analyzed separately; the results showed that compared with good and fast collaterals, a similar risk ratio was found for patients with good-but-slow collaterals (risk ratio, 1.3; 95% CI, 0.7-2.4). CONCLUSIONS: Dynamic CTA provides a more detailed assessment of collaterals than single-phase CTA and has a stronger relationship with infarct volume at follow-up. The extent of collateral flow is more important in determining tissue fate than the velocity of collateral filling. The timing of dynamic CTA acquisition in relation to intravenous contrast administration is critical for the optimal assessment of the extent of collaterals.

A blinded randomized assessment of laser Doppler flowmetry efficacy in standardizing outcome from intraluminal filament MCAO in the rat.

BACKGROUND: Laser Doppler flowmetry (LDF) is widely used for estimating cerebral blood flow changes during intraluminal middle cerebral artery occlusion (MCAO). No investigation has systematically examined LDF efficacy in standardizing outcome. We examined MCAO histologic and behavioral outcome as a function of LDF measurement. MATERIALS AND METHODS: Rats were subjected to 90min MCAO by 4 surgeons having different levels of MCAO surgical experience. LDF was measured in all rats during ischemia. By random assignment, LDF values were (Assisted) or were not (Blinded) made available to each surgeon during MCAO (n=12-17 per group). Neurologic and histologic outcomes were measured 7 days post-MCAO. A second study examined LDF effects on 1-day post-MCAO outcome. RESULTS: Pooled across surgeons, intra-ischemic %LDF change (P=0.12), neurologic scores (Assisted vs. Blinded=14±6 vs. 13±7, P=0.61, mean±standard deviation) and cerebral infarct volume (162±63mm(3)vs. 143±86mm(3), P=0.24) were not different between groups. Only for one surgeon (novice) did LDF use alter infarct volume (145±28mm(3)vs. 98±61mm(3), P=0.03). LDF use decreased infarct volume coefficient of variation (COV) by 35% (P=0.02), but had no effect on neurologic score COV. COMPARISON WITH EXISTING METHODS: We compared intraluminal MCAO outcome as a function of LDF use. CONCLUSIONS: LDF measurement altered neither neurologic nor histologic MCAO outcome. LDF did not decrease neurologic deficit COV, but did decrease infarct volume COV. LDF may allow use of fewer animals if infarct volume is the primary dependent variable, but is unlikely to impact requisite sample sizes if neurologic function is of primary interest.

An integrated stroke model with a consistent penumbra for the assessment of neuroprotective interventions.

BACKGROUND/AIM: A longer period of vessel occlusion reduces the coefficient of variation of the infarct lesion size ['infarct variation coefficient' (IVC)] due to a gradual expansion of the lesion within a limited territory defined by the vascular anatomy, but it increases the mortality rate. A crucial issue in the induction of experimental focal cerebral ischemia has been to achieve a low IVC value and a low mortality rate. We attempted to improve IVC and mortality using the 3-vessel occlusion model. METHODS: We introduced a new, transtemporal fascia approach to expose the zygomatic arch, in which the fascia of the temporal muscle is cut and retracted dorsally together with the facial nerve and the vein en bloc. RESULTS/CONCLUSION: The approach avoided traumatic venous bleeding around the zygomatic arch. We established a bloodless model of focal ischemia that can produce a consistent degree of reduction in the regional cerebral blood flow within the ischemic penumbra. The model, characterized by a 15-min ischemia, an IVC of 15-21%, and low mortality after ischemia, is expected to produce reliable preclinical evidence in the assessment of neuroprotective interventions for ischemic stroke. The entire procedure is presented in the online supplementary video (www. karger.com/doi/10.1159/000356048).

Assessment of behavioral flexibility after middle cerebral artery occlusion in mice.

Middle cerebral artery occlusion (MCAO) is the most common animal model of cerebral ischemia and induces various functional impairments. Long-lasting deficits resulting from MCAO however, remain insufficiently characterized, especially regarding cognition. Yet, behavioral flexibility, a prominent cognitive process is found impaired after stroke in humans. We thus used an operant-based task to assess behavioral flexibility in mice after MCAO. Three weeks after 30 min MCAO surgery, mice were subjected to a battery of sensorimotor tests (rotarod, vertical pole test, spontaneous locomotion and grip-strength test). Behavioral flexibility was then assessed in an operant task, in which mice, rewarded according to a FR5 schedule of reinforcement, had to alternate their operant responses between two levers from trial to trial. Regarding sensory and motor functioning, only the pole test yielded a significant difference between MCAO and sham mice. In the operant flexibility task, results showed a behavioral flexibility deficit in MCAO mice; neither the operant response acquisition nor the appeal for food rewards was altered. In conclusion, our operant-based task revealed a long-lasting behavioral flexibility deficit after MCAO in mice.

Xenon-enhanced CT assessment of cerebral blood flow in stroke-in-progress patients with unilateral internal carotid artery or middle cerebral artery stenosis.

Carotid or cerebral artery stenosis resulting in low perfusion is a major cause of ischemic stroke. Understanding the unique hemodynamic features in each patient undergoing a stroke-in-progress (SIP) and the correlation between progression and cerebral blood flow (CBF) status would help in the diagnosis and treatment of individual patients. We used xenon-enhanced CT (Xe-CT) to examine cerebral perfusion in patients with or without SIP (30 patients/group), recruited from October 2009 to October 2010. Only SIP patients with unilateral stenosis in the internal or middle cerebral artery were recruited. The occurrence of watershed infarction was higher in the SIP group than in the non-SIP group (P <0.05). In the SIP group, larger hypoperfused areas were found around the lesions than in the non-SIP group. In the SIP group, the CBF values in the ipsilateral areas were significantly lower than those in corresponding regions on the contralateral side. CBF values in the contralateral hemisphere were significantly lower in the SIP group than in the non-SIP group. In SIP patients, infarctions were surrounded by larger hypoperfused areas than in non-SIP patients. These larger hypoperfused areas may result in pathological damage to the brain that is responsible for the progression of stroke.

Assessment of cortical hemodynamics by multichannel near-infrared spectroscopy in steno-occlusive disease of the middle cerebral artery.

BACKGROUND AND PURPOSE: In a pilot study we evaluated near-infrared spectroscopy as to its potential benefit in monitoring patients with steno-occlusive disease of a major cerebral artery for alterations in cortical hemodynamics. METHODS: Cortical maps of time-to-peak (TTP) in 10 patients unilaterally affected by severe stenosis or occlusion of the middle cerebral artery were acquired by multichannel near-infrared spectroscopy after bolus application of indocyanine green. Hemodynamic manifestations were assessed by comparison between affected and unaffected hemisphere and evaluated for common constituents by principal component analysis. In one patient, TTP values were compared with those obtained by dynamic susceptibility contrast imaging. RESULTS: TTP was increased on the affected hemisphere in 9 patients. Mean difference in TTP between hemispheres was 0.44 second (P<0.05) as compared with a mean lateral difference of 0.12 second found in a control group of 10 individuals. In group analysis a significant rise in TTP was found in the distribution of the affected middle cerebral artery, whereas principal component analysis suggests augmentation of hemodynamic effects toward the border zones as a dominant pattern. A linear correlation of 0.61 between TTP values determined by dynamic susceptibility contrast MRI and near-infrared spectroscopy was found to be statistically significant (P<0.001). CONCLUSIONS: Multichannel near-infrared spectroscopy might facilitate detection of disease-related hemodynamic changes as yet only accessible by tomographic imaging modalities. Being indicative for hypoperfusion and collateral flow increased values of TTP, as found to a varying extent in the present patient group, might be of clinical relevance.

MRI assessment of amplitude of low-frequency fluctuation in rat brains with acute cerebral ischemic stroke.

To investigate fluctuations in the amplitude of low-frequency blood oxygenation level-dependent (BOLD) fMRI during acute brain ischemia, and to evaluate the use of amplitude of low-frequency fluctuations (ALFFs) in resting state fMRI for assessing super-acute focal cerebral ischemic stroke. A super-acute stroke model with middle cerebral artery occlusion (MCAO) in the rat was employed. Spontaneous fluctuations were recorded using a series of gradient echo-planar imaging (EPI) images before and 30 min, 60 min, 2 h, 6 h, 12 h, and 24 h after MCAO. After preprocessing, serial fMRI data were obtained by fast Fourier transformation to calculate the ALFFs. Statistical parametric mapping software was used for the statistical analysis of ALFFs. T2-weighted images and diffusion weighted images (DWI) were also performed to detect the ischemic lesion. The signal intensities of abnormal ALFFs increased and migrated from the core of the ischemic lesion areas to the edge of lesion following MCAO. The dynamic changes in the ALFF maps demonstrated that the sizes of the ALFF regions exceeded beyond the borderline of the DWI lesions during the super-acute ischemic stroke stage. There was a significant difference in the ALFFs maps between the ischemic stroke group and the control group (P<0.005; cluster size>10 voxels), which mainly occurred in the periphery of the ischemic region in the cortex. These data suggest that ALFF maps provide hemodynamic BOLD information on neural activity, and have potential for predicting survival and prognosis of acute ischemic brain tissues.

Noninvasive assessment of cerebral perfusion and oxygenation in acute ischemic stroke by near-infrared spectroscopy.

BACKGROUND: In acute stroke patients, there is a need for noninvasive measurement to monitor blood flow-based therapies. We investigated the utility of near-infrared spectroscopy (NIRS) to determine cerebral perfusion in these patients. METHODS: Eleven patients were investigated within 1.4 +/- 2.2 days after onset of an ischemic middle cerebral artery infarction by monitoring the kinetics of an intravenous bolus of indocyanine green (ICG). For ICG kinetics, bolus peak time, time to peak (TTP = time between 0 and 100% ICG maximum), maximum ICG concentration, rise time (time between 10 and 90% ICG maximum), slope (maximum ICG/TTP), and blood flow index (BFI = maximum ICG/rise time) were obtained. Perfusion-weighted MRI (PWI) and NIRS measurements were performed within 24 h, and the interhemispherical differences of TTP values were compared. RESULTS: Stroke patients showed an increased bolus peak time (p < 0.02), TTP (p < 0.01), and rise time (p < 0.01), whereas slope (p < 0.01) and BFI (p < 0.01) were diminished at the site of infarction as compared to the unaffected hemisphere. The interhemispherical differences of TTP as measured by PWI and NIRS were closely correlated (r = 0.86). CONCLUSIONS: Noninvasive measurements of cerebral ICG kinetics by NIRS provide a useful means of detecting cerebral perfusion deficits in patients with acute stroke, which correlate well with those obtained by PWI.

Neither in vivo MRI nor behavioural assessment indicate therapeutic efficacy for a novel 5HT(1A) agonist in rat models of ischaemic stroke.

BACKGROUND: 5HT1A agonists have previously been shown to promote recovery in animal models of stroke using ex vivo outcome measures which have raised the hopes for a potential clinical implementation. The purpose of this study was to evaluate the potential neuroprotective properties of a novel 5HT1A agonist DU123015 in 2 different models of transient focal ischaemic stroke of varying severities using both in vivo neuroimaging and behavioural techniques as primary outcome measures. For these studies, the NMDA receptor antagonist MK-801 was also utilized as a positive control to further assess the effectiveness of the stroke models and techniques used. RESULTS: In contrast to MK-801, no significant therapeutic effect of DU123015 on lesion volume in either the distal MCAo or intraluminal thread model of stroke was found. MK-801 significantly reduced lesion volume in both models; the mild distal MCAo condition (60 min ischaemia) and the intraluminal thread model, although it had no significant impact upon the lesion size in the severe distal MCAo condition (120 min ischaemia). These therapeutic effects on lesion size were mirrored on a behavioural test for sensory neglect and neurological deficit score in the intraluminal thread model. CONCLUSION: This study highlights the need for a thorough experimental design to test novel neuroprotective compounds in experimental stroke investigations incorporating: a positive reference compound, different models of focal ischaemia, varying the duration of ischaemia, and objective in vivo assessments within a single study. This procedure will help us to minimise the translation of less efficacious compounds.

Post-ischemic leakiness of the blood-brain barrier: a quantitative and systematic assessment by Patlak plots.

The Patlak plot analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows estimation of blood-brain barrier (BBB) leakage following temporary focal cerebral ischemia. Thus far, a systematic and quantitative in vivo evaluation of post-ischemic BBB leakage is lacking. Here, using DCE-MRI and the Patlak plot method, we quantitatively assessed BBB leakage in rats at the following time-points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. Sham-operated animals served as controls. Data collected for each time-point were: the blood-to-brain transfer rate constant (K(i)) of the contrast agent gadolinium, distribution volume (V(p)), ischemic lesion volume, and apparent diffusion coefficient (ADC) values. Compared to controls, K(i), measured at all time-points, except for 5 weeks, appeared significantly different (p<0.001). At several time-points (25 min, 48 and 72 h, 4 and 5 weeks), V(p) was similar compared to that of controls, but for the remaining groups the difference was significant (p<0.001). Analyzing the relationship of K(i) values to time-points, we observed a trend towards a decrease over time (r=-0.61, p=0.014). Both ADC values (r=-0.58, p=0.02) and ischemic lesion volumes (r=0.75, p=0.0015) correlated with K(i) values. These results suggest that after ischemia-reperfusion in rats, BBB leakage is continuous during a 4-week period. Its magnitude diminishes over time and correlates with severity and extent of ischemic injury.

[A proposal of a neuropsychological and quality of life assessment protocol in patients with malignant middle cerebral artery infarction]. / Propuesta de un protocolo de valoración neuropsicológica y de calidad de vida en pacientes que han sufrido un infarto maligno de la arteria cerebral media.

Malignant middle cerebral artery infarction (MMCAI) refers to an infarction type normally accompanied by massive cerebral edema, and associated with a high mortality rate under conventional therapeutic measures. Both moderate hypothermia and decompressive hemicraniectomy have been shown to significantly improve survival rate, although controversy still persists regarding the criteria for the selection of patients that could benefit from this type of treatment, and whether application of these measures is justified given the residual sequelae. In our centre, both measures are being applied simultaneously for the first time in humans. The present work is a literature review on the results of moderate hypothermia application and decompressive surgical techniques in patients suffering from MMCAI. We also introduce our management scheme for handling these patients in our centre, and propose a final result evaluation protocol that is easily applied in a clinical setting. This protocol includes an evaluation of patients with ischemic lesions specific for the right or left hemisphere, and allows for the description of specific neuropsychological sequelae and their repercussions on patients' quality of life.

Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: effects on BBB breakdown and MMP expression in the acute and subacute phase.

Reperfusion injury is a complication of recanalization therapies after focal cerebral ischemia. The disruption of the blood-brain barrier (BBB) caused by up-regulated metalloproteinases (MMPs) can lead to edema and hemorrhage. Middle cerebral artery occlusion (MCAO=90 min) and reperfusion (R=24 h vs. 5 days) was induced in male Wistar rats. Rats were randomized in four groups: (1) control (C), (2) twice daily minocycline (30 mg/kg bodyweight) every day (M), (3) hypothermia (33 degrees C) for 4 h starting 60 min after occlusion (H), (4) combination of groups 2 and 3 (MH). Serial MRI was performed regarding infarct evolution and BBB disruption, MMP-2 and MMP-9 were assessed by zymography of serum and ischemic brain tissue, and a functional neuroscore was done at 24 h and 5 days. M and H reduced both infarct sizes, volume and signal intensity of BBB breakdown and improved neuroscore at all points in time to the same extent. This was most likely due to inhibition of MMP-2 and MMP-9. The presence of MMP-9 at 24 h or MMP-2 at 5 days in brain tissue correlated with BBB breakdown whereas serum MMP-2- and -9 showed no relationship with BBB breakdown. The combination MH had a small but not significantly additional effect over the single treatments. Minocycline seems to be as neuroprotective as hypothermia in the acute and subacute phase after cerebral ischemia. One essential mechanism is the inhibition of MMPs. The combination therapy is only slightly superior. The net effect of MMPs inhibition up to 5 days after focal cerebral ischemia is still beneficial.

Alberta Stroke Program Early CT Scoring of CT perfusion in early stroke visualization and assessment.

BACKGROUND AND PURPOSE: Qualitative CT perfusion (CTP) assessment by using the Alberta Stroke Program Early CT Score (ASPECTS) allows rapid calculation of infarct extent for middle cerebral artery infarcts. Published thresholds exist for noncontrast CT (NCCT) ASPECTS, which may distinguish outcome/complication risk, but early ischemic signs are difficult to detect. We hypothesized that different ASPECTS thresholds exist for CTP parameters versus NCCT and that these may be superior at predicting clinical and radiologic outcome in the acute setting. MATERIALS AND METHODS: Thirty-six baseline acute stroke NCCT and CTP studies within 3 hours of symptoms were blindly reviewed by 3 neuroradiologists, and ASPECTS were assigned. Treatment response was defined as major neurologic improvement when a > or =8-point National Institutes of Health Stroke Scale improvement at 24 hours occurred. Follow-up NCCT ASPECTS and 90-day modified Rankin score (mRS) were radiologic and clinical reference standards. Receiver operating characteristic curves derived optimal thresholds for outcome. RESULTS: Cerebral blood volume and NCCT ASPECTS had similar radiologic correlations (0.6 and 0.5, respectively) and best predicted infarct size in the absence of major neurologic improvement. A NCCT ASPECT threshold of 7 and a cerebral blood volume threshold of 8 discriminated patients with poor follow-up scans (P < .0002 and P = .0001) and mRS < or =2 (P = .001 and P < .001). Only cerebral blood volume predicted major neurologic improvement (P = .02). Interobserver agreement was substantial (intraclass correlation coefficient, 0.69). Cerebral blood volume ASPECTS sensitivity, specificity, positive predictive value, and negative predictive value for clinical outcome were 60%, 100%, 100%, and 45%, respectively. No patients with cerebral blood volume ASPECTS <8 achieved good clinical outcome. CONCLUSION: Cerebral blood volume ASPECTS is equivalent to NCCT for predicting radiologic outcome but may have an additional benefit in predicting patients with major neurologic improvement.

The Eligible study: ultrasound assessment in acute ischemic stroke within 3 hours.

AIMS OF THE STUDY: to identify with echo color Doppler ultrasound of the supra-aortic vessels and transcranial color-coded duplex sonography (TCCD) various patterns of vessel occlusion within 3 h from stroke onset, to compare each group defined at the admission with clinical findings and outcome, and to study the recanalization process, independent of therapy. METHODS: We enrolled 89 consecutive patients (mean age 68.9 years). Ultrasound evaluation was done within 3 h from stroke onset, and was repeated at 3-6 and 24-36 h, at day 5, and at 3 months. At admission, patients were divided into the following groups: internal carotid artery occlusions and stenoses (<50%, 50-69%, > or =70%, near occlusion), middle cerebral artery stenoses and occlusions, tandem occlusions and T occlusions. Vascular recanalization in each group was evaluated. Subgroups were compared for NIH Stroke Scale (NIHSS) and the outcome measures mortality, Barthel index (BI) and modified Rankin scale (mRS). Favorable outcome was defined as mRS < or =2 and BI > or =90. RESULTS: Each subgroup differed significantly for baseline NIHSS (p < 0.0001), 3-month mortality (p = 0.0235), BI at day 5 (p = 0.0458) and mRS at 3 months (p = 0.0028), even after adjustment for treatment. T and tandem occlusions were the subgroups with the highest NIHSS scores and the poorest outcomes, and the same subgroups had the worst recanalization rates. CONCLUSIONS: TCCD in the acute setting of stroke patients allows identification of the presence and site of clots, prediction of outcome and study of the dynamic process of vessel recanalization, in both the acute phase and follow-up.

Pre- and post-right middle cerebral artery stroke in a young adult: a case study examining the sensitivity of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Right-hemisphere strokes are associated with a number of neurobehavioral deficits. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a relatively new, but widely used screening battery; however, there is little published research in patients who have sustained strokes. We present a rare case of stroke in a 22-year-old psychiatric patient, who received neuropsychological evaluations before and after sustaining a right middle cerebral artery (MCA) stroke. The RBANS demonstrated sensitivity to post-stroke changes despite pre-stroke cognitive impairments and a complex psychiatric overlay, with the Visuospatial/Constructional index being one of the most sensitive indicators of right hemisphere dysfunction. Line Orientation fell from normal to defective levels; these findings were associated with decline in related standard neuropsychological measures.