Ischemia in intracerebral hemorrhage: A comparative study of small-vessel and large-vessel diseases.

OBJECTIVE: This study aimed to compare effects of cerebral small-vessel disease (cSVD) burden and cerebral artery stenosis (CAS) on acute ischemia in intracerebral hemorrhage (ICH) and their interaction with mean arterial pressure (MAP) change. METHODS: We recruited consecutive patients with acute primary ICH. Brain magnetic resonance imaging and angiography were performed to quantify diffusion-weighted imaging (DWI) lesions, CAS, and cSVD markers, which were calculated for the total cSVD score. Multivariable regression models were adopted to explore their associations by DWI lesions size (<15 vs. ≥15 mm) and median MAP change stratification. RESULTS: Of 305 included patients (mean age 59.5 years, 67.9% males), 77 (25.2%) had DWI lesions (small, 79.2%; large, 20.8%) and 67 (22.0%) had moderate and severe CAS. In multivariable analysis, small DWI lesions were independently associated with higher total cSVD score (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.36-2.41). and large DWI lesions were associated with more severe CAS (OR 2.51, 95% CI 1.17-5.38). This association was modified by MAP change (interaction p = 0.016), with stratified analysis showing an increased risk of large DWI lesions in severe CAS with greater MAP change (≥44 mmHg) (OR 3.48, 95% CI 1.13-10.74) but not with mild MAP change (<44 mmHg) (OR 1.21, 95% CI 0.20-7.34). INTERPRETATION: Total cSVD burden is associated with small DWI lesions, whereas the degree of CAS is associated with large DWI lesions, specifically with greater MAP change, suggesting that large-artery atherosclerosis may be involved in ischemic brain injury, which is different from small-vessel pathogenesis in ICH.

Vitamin B6 prevents Isocarbophos-induced posterior cerebral artery injury in offspring rats through up-regulating S1P receptor expression.

We have previously reported that the long-term exposure of Isocarbophos, a kind of organophosphorus compounds, induces vascular dementia (VD) in rats. Studies have also shown that organophosphorus compounds have adverse effects on offsprings. Vitamin B6 is a coenzyme mainly involved in the regulation of metabolism and has been demonstrated to ameliorate VD. Sphingosine-1-phosphate (S1P), a biologically active lipid, plays a vital role in the cardiovascular system. However, whether S1P is involved in the therapeutic effects of Vitamin B6 on posterior cerebral artery injury has yet to be further answered. In the present study, we aimed to explore the potential influence of Vitamin B6 on Isocarbophos-induced posterior cerebral artery injury in offspring rats and the role of the S1P receptor in this process. We found that Vitamin B6 significantly improves the vasoconstriction function of the posterior cerebral artery in rats induced by Isocarbophos by the blood gas analysis and endothelium-dependent relaxation function assay. We further demonstrated that Vitamin B6 alleviates the Isocarbophos-induced elevation of ICAM-1, VCAM-1, IL-1, and IL-6 by using the enzyme-linked immunosorbent assay kits. By performing immunofluorescence and the western blot assay, we revealed that Vitamin B6 prevents the down-regulation of S1P in posterior cerebral artery injury. It is worth noting that Fingolimod, the S1P inhibitor, significantly inhibits the Vitamin B6-induced up-regulation of S1P in posterior cerebral artery injury. Collectively, our data indicate that Vitamin B6 may be a novel drug for the treatment of posterior cerebral artery injury and that S1P may be a drug target for its treatment.

Mechanical Thrombectomy for Distal Occlusions: Efficacy, Functional and Safety Outcomes: Insight from the STAR Collaboration.

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for the treatment of proximal anterior circulation large vessel occlusions. However, little is known about its efficacy and safety in the treatment of distal intracranial occlusions. METHODS: This is a multicenter retrospective study of patients treated with MT at 15 comprehensive centers between January 2015 and December 2018. The study cohort was divided into 2 groups based on the location of occlusion (proximal vs. distal). Distal occlusion was defined as occlusion of M3 segment of the middle cerebral artery, any segment of the anterior cerebral artery, or any segment of the posterior cerebral artery. Only isolated distal occlusion was included. Good outcome was defined as 90-day modified Rankin scale score 0-2. RESULTS: A total of 4710 patients were included in this study, of whom 189 (4%) had MT for distal occlusions. Compared with the proximal occlusion group, distal occlusion group had a higher rate of good outcome (45% vs. 36%; P = 0.03) and a lower rate of successful reperfusion (78% vs. 84%; P = 0.04). However, the differences did not retain significance in adjusted models. Otherwise there was no difference in the rate of hemorrhagic complications, mortality, or procedure-related complications between the 2 groups. Successful reperfusion, age, and admission stroke severity emerged as predictors of good functional outcome in the distal occlusion group. CONCLUSIONS: Thrombectomies of distal vessels achieve high rate of successful reperfusion with similar safety profile to those in more proximal locations.

A connectome-based approach to assess motor outcome after neonatal arterial ischemic stroke.

OBJECTIVE: Studies of motor outcome after Neonatal Arterial Ischemic Stroke (NAIS) often rely on lesion mapping using MRI. However, clinical measurements indicate that motor deficit can be different than what would solely be anticipated by the lesion extent and location. Because this may be explained by the cortical disconnections between motor areas due to necrosis following the stroke, the investigation of the motor network can help in the understanding of visual inspection and outcome discrepancy. In this study, we propose to examine the structural connectivity between motor areas in NAIS patients compared to healthy controls in order to define the cortical and subcortical connections that can reflect the motor outcome. METHODS: Thirty healthy controls and 32 NAIS patients with and without Cerebral Palsy (CP) underwent MRI acquisition and manual assessment. The connectome of all participants was obtained from T1-weighted and diffusion-weighted imaging. RESULTS: Significant disconnections in the lesioned and contra-lesioned hemispheres of patients were found. Furthermore, significant correlations were detected between the structural connectivity metric of specific motor areas and manuality assessed by the Box and Block Test (BBT) scores in patients. INTERPRETATION: Using the connectivity measures of these links, the BBT score can be estimated using a multiple linear regression model. In addition, the presence or not of CP can also be predicted using the KNN classification algorithm. According to our results, the structural connectome can be an asset in the estimation of gross manual dexterity and can help uncover structural changes between brain regions related to NAIS.

To what degree is late life cognitive decline driven by age-related neuropathologies?

The ageing brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease, infarcts, and Lewy bodies, account for ∼40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline [e.g. limbic predominant age-related TDP-43 encephalopathy (LATE-NC), hippocampal sclerosis, other cerebrovascular conditions]. We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. Deceased participants (n = 1164) from two longitudinal clinical-pathological studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathological examinations provided 11 pathological indices, including markers of Alzheimer's disease, non- Alzheimer's disease neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathological indices with global cognitive decline, and random change point models examined the relation of the pathological indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = -0.101, SE = 0.003, P < 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, P < 0.001). When considered separately, 10 of 11 pathological indices were associated with faster decline and accounted for between 2% and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathological indices together accounted for 43% of the variation in decline; Alzheimer's disease-related indices accounted for 30-36% of the variation, non-Alzheimer's disease neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathological indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive ageing and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.

Association between CYP2C19 polymorphisms and clinical outcomes in patients undergoing stent procedure for cerebral artery stenosis.

We investigated the effect of CYP2C19 polymorphisms on the clinical outcomes of clopidogrel therapy in patients after stenting procedure for cerebral artery stenosis in northeast China. 568 patients performed CYP2C19 genotype screening in the neurosurgery department of our hospital; 154 patients were finally recruited according to the inclusion and exclusion criteria, and followed-up for 6 months. Ischemic events including (1) transient ischemic attack (TIA); (2) stent thrombosis; (3) ischemic stroke; and (4) death were defined as primary clinical endpoints. The frequencies of CYP2C19*1, *2 and *3 alleles in 568 patients were 63.1%, 31.1% and 5.8%, respectively. 154 patients were classified into extensive (65 patients; 42.2%), intermediate (66 patients; 42.9%), and poor (23 patients; 14.9%) metabolizer groups. A χ2 test showed a significant difference in primary clinical endpoints at 6 months (P = 0.04), and a multivariate Cox regression analysis indicated that the CYP2C19 loss-of-function (LOF) alleles associated with post-procedure prognosis. The Kaplan-Meier curve revealed that there was no significant difference in ischemic events between *2 and *3 alleles carriers. Our study verifies that CYP2C19 *2 and *3 have significant impact on the clinical outcomes of clopidogrel therapy in patients with stenting procedure for cerebral artery stenosis in China.

Susceptibility-Weighted Imaging in Neurodegenerative Disorders: A Review.

As human life expectancy increases, there is an increased prevalence of neurodegenerative disorders and dementia. There are many ongoing research trials for early diagnosis and management of dementia, and neuroimaging is a critical part of such studies. However, conventional neuroimaging often fails to provide enough diagnostic findings in patients with neurodegenerative disorders. In this context, different MRI sequences are currently under investigation to facilitate the accurate diagnosis of such disorders. Susceptibility-weighted imaging (SWI) is an innovative MRI technique that utilizes "magnitude" and "phase" images to produce an image contrast that is sensitive for the detection of susceptibility differences of the tissues. As many neurodegenerative disorders are associated with accelerated iron deposition and/or microhemorrhages in different parts of the brain, SWI can be applied to detect these diagnostic clues. For instance, in cerebral amyloid angiopathy, SWI can demonstrate cortical microhemorrhages, which are predominantly in the frontal and parietal regions. Or in Parkinson disease, abnormal swallow-tail sign on high-resolution SWI is highly diagnostic. Also, SWI is a useful sequence to detect the low signal intensity of precentral cortices in patients with amyotrophic lateral sclerosis. Being familiar with SWI findings in neurodegenerative disorders is critical for an accurate diagnosis. In this paper, the authors review the technical parameters of SWI, physiologic, and pathologic iron deposition in the brain, and the role of SWI in the evaluation of neurodegenerative disorders in daily practice.

Validation of the focal cerebral arteriopathy severity score (FCASS) in a Swiss cohort: Correlation with infarct volume and outcome.

BACKGROUND: Focal cerebral arteriopathy (FCA), a major cause of childhood arterial ischemic stroke (AIS), can progress and lead to increased infarct size and/or recurrent stroke. Evaluating treatment options depends on the ability to quantify reliably the degree of stenosis in FCA. AIMS: We validated the recently introduced FCA severity score (FCASS) in an independent cohort from the Swiss Neuro-Paediatric Stroke Registry (SNPSR). MATERIALS AND METHODS: We included children with FCA who had MR or CT angiography and a Pediatric Stroke Outcome Measure (PSOM) at 6-months and 2-years post-stroke. A paediatric neuroradiologist applied the FCASS and the modified pediatric Alberta Stroke Program Early Computed Tomography Score (ASPECTS), a measure of infarct volume, to all available imaging. Two senior paediatric stroke neurologists and a neuroradiology fellow independently assigned FCASS scores to test interrater reliability. Pairwise correlations between FCASS, pedASPECTS, and PSOM were examined. RESULTS: Thirty-two children [median (IQR) age = 5.9 (1.8, 9.6), 19 males] were included. The median maximum FCASS score at any time was 9 (IQR 6, 12; range 3, 16). Larger infarct volume scores correlated with both higher maximum FCASS scores and worse post-stroke outcomes, although we found no direct correlation between FCASS and outcomes. Stroke neurologists tended to assign lower FCASS scores than the neuroradiologist, but interrater reliability was predominantly good. CONCLUSIONS: In this independent validation cohort, higher maximum FCASS correlated with greater infarct volume scores that also correlated with worse neurological outcomes. Scoring by non-imaging specialists seems to be valuable, although differences are present.

Vessel Wall Enhancement and Focal Cerebral Arteriopathy in a Pediatric Patient with Acute Infarct and COVID-19 Infection.

Herein, we report the findings of intracranial arterial wall enhancement, consistent with focal cerebral arteriopathy-inflammatory type, in a child presenting with acute infarct in the setting of coronavirus disease 2019 (COVID-19) infection. To our knowledge, this report provides the first description of vessel wall imaging findings in COVID-19-associated acute stroke.

Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease.

Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.

Dilated Cerebral Arteriopathy in Classical Pompe Disease: A Novel Finding.

BACKGROUND: In Pompe disease, glycogen deposition results in an augmentation of blood flow and abnormal remodeling, with resultant weakening of the arterial walls, which may result in pathologic dilatation of the cerebral arteries. This complication is rare in patients with late-onset Pompe disease, but it has not been well-described in infantile-onset Pompe disease. The effect of enzyme replacement therapy on this process is not known. METHODS: We examined clinical and imaging data on two patients who exhibit cerebrovascular arteriopathy: a 14-year-old boy with infantile-onset Pompe disease on enzyme replacement therapy and a 23-year-old woman with late-onset Pompe disease who was also receiving enzyme replacement therapy. RESULTS: Our 14-year-old patient exhibits cerebrovascular arteriopathy, primarily proximal and vertebrobasilar, while the 23-year-old patient has a more diffuse pattern. The 14-year-old patient is unique because cerebral dolichoectasias have not been described in infantile-onset Pompe disease. The 23-year-old patient is notable given the age and history of enzyme replacement therapy since age 15 years. CONCLUSIONS: Dilative cerebral arteriopathy in infantile-onset Pompe disease is novel and similarly atypical is the diffuse vascular dilation seen in our young patient with late-onset Pompe disease, both receiving enzyme replacement therapy. We should be cognizant of the risk of cerebrovascular disease in Pompe disease regardless of the disease variant and enzyme replacement therapy status.

Wallerian Degeneration of the Cerebral Peduncle and Association with Motor Outcome in Childhood Stroke.

BACKGROUND: To evaluate the presence of Wallerian degeneration and its relationship with sensorimotor deficits following childhood-onset arterial ischemic stroke (AIS). METHODS: Children surviving unilateral AIS older than one month of age were assessed for severity of sensorimotor neurological deficit with the Pediatric Stroke Outcome Measure at least one year post stroke (mean follow-up = 2.9 years, S.D. = ±1.6). The area (mm3) of each cerebral peduncle was measured on T2-weighted magnetic resonance images to calculate an Asymmetry Index (AI). The AI between patients with childhood stroke (cases) and controls (children with normal MRI) was compared. In the stroke group, the AI between patients with good and poor motor outcome, and the correlation between the AI and motor outcome was calculated. RESULTS: Asymmetry was compared in 52 children with stroke (cases) and 20 controls (normal brain MRIs). The AI was greater in patients with stroke (mean = 6.8%, S.D. = ±5.9) compared with controls (mean = 3.4%, S.D. = ±3.5, P < 0.02). Patients with poor outcome had an AI of 10% or greater compared with patients with good outcome (mean 10.4 versus 4, P < 0.001), and the AI was moderately correlated with motor deficit severity (r = 0.582, P = 0.001). CONCLUSIONS: Asymmetry of the cerebral peduncle is a feasible method of assessing Wallerian degeneration in children with unilateral AIS. The degree of asymmetry in the cerebral peduncles was moderately correlated with neurological outcome severity and reflects the degree of motor deficit in children following stroke.

Artery occlusion independently predicts unfavorable outcome in cervical artery dissection.

OBJECTIVE: To assess the impact of dissected artery occlusion (DAO) on functional outcome and complications in patients with cervical artery dissection (CeAD). METHODS: We analyzed combined individual patient data from 3 multicenter cohorts of consecutive patients with CeAD (the Cervical Artery Dissection and Ischemic Stroke Patients [CADISP]-Plus consortium dataset). Patients with data on DAO and functional outcome were included. We compared patients with DAO to those without DAO. Primary outcome was favorable functional outcome (i.e., modified Rankin Scale [mRS] score 0-1) measured 3-6 months from baseline. Secondary outcomes included delayed cerebral ischemia, major hemorrhage, recurrent CeAD, and death. We performed univariate and multivariable binary logistic regression analyses and calculated odds ratios (OR) with 95% confidence intervals (CI), with adjustment for potential confounders. RESULTS: Of 2,148 patients (median age 45 years [interquartile range (IQR) 38-52], 43.6% women), 728 (33.9%) had DAO. Patients with DAO more frequently presented with cerebral ischemia (84.6% vs 58.5%, p < 0.001). Patients with DAO were less likely to have favorable outcome when compared to patients without DAO (mRS 0-1: 59.6% vs 80.1%, p unadjusted < 0.001). After adjustment for age, sex, and initial stroke severity, DAO was independently associated with less favorable outcome (mRS 0-1: OR 0.65, CI 0.50-0.84, p = 0.001). Delayed cerebral ischemia occurred more frequently in patients with DAO than in patients without DAO (4.5% vs 2.9%, p = 0.059). CONCLUSION: DAO independently predicts less favorable functional outcome in patients with CeAD. Further research on vessel patency, collateral status and effects of revascularization therapies particularly in patients with DAO is warranted.

Non-traumatic cervical artery dissection and ischemic stroke: A narrative review of recent research.

Cervical artery dissection (CAD) is a leading cause of ischaemic stroke (IS) in young and middle-aged adults. Despite well characterized clinical presentation, the diagnosis of CAD can be quite challenging due to a wide variety of symptoms ranging from minor neck pain to severe neurological symptoms. Invasive diagnostic procedures such as DSA are nowadays being replaced by the sensitive and CAD-specific sequences of MR. The most recent studies confirmed the overall efficacy of antiplatelet and anticoagulant therapies for CAD patients is equivalent, although patients should be qualified for concrete treatment on the basis of recently characterized clinical features. The use of NOAC in CAD-related IS prevention cannot yet be recommended due to the lack of evidences from randomized controlled trials. Endovascular therapies should be considered as the treatment of CAD, especially in the cases of large occlusion or antithrombotic treatment failure. Further research is needed to evaluate the efficacy of new imaging modalities and treatment options. This review summarize the last 5-year development of the diagnosis and treatment for CAD as a causative factor for IS.

Sex Differences in Management and Outcomes of Acute Ischemic Stroke With Large Vessel Occlusion.

Background and Purpose- Sex differences in the management and outcomes of acute ischemic stroke with large vessel occlusion are unknown in the era of endovascular therapy (EVT). This study investigated these differences in the RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism)-Japan Registry 2 patient database. Methods- RESCUE-Japan Registry 2 registered patients with large vessel occlusion who were admitted within 24 hours of onset were enrolled in this study. We estimated the likelihood to receive EVT according to sex. The primary outcome was good outcome defined as a modified Rankin Scale score of 0 to 2 at 90 days after onset. Secondary outcomes were mortality within 90 days, any or symptomatic intracranial hemorrhage within 72 hours, and recurrence of stroke or transient ischemic attack within 90 days. Results- Among 2399 patients, 1087 patients were female and 1312 were male; 47.9% of females and 57.7% of males received EVT (adjusted odds ratio, 0.71; 95% CI, 0.59-0.86). Good outcome was observed in 27.3% and 44.2% of the females and males, respectively ( P<0.0001). The adjusted odds ratio of a good outcome in females was 0.80 (95% CI, 0.65-0.99). Mortality was 12.3% and 9.9% in females and males, respectively ( P=0.06); the adjusted odds ratio was 0.78 (95% CI, 0.58-1.05). Conclusions- Females with acute ischemic stroke with large vessel occlusion showed poor functional outcome compared to males. Females were less likely to receive EVT; lower utilization of EVT accounted for a portion of the poor outcome.

Selective neuronal damage and blood pressure in atherosclerotic major cerebral artery disease.

OBJECTIVE: In patients with atherosclerotic major cerebral artery disease, low blood pressure might impair cerebral perfusion, thereby exacerbate the risk of selective neuronal damage. The purpose of this retrospective study was to determine whether low blood pressure at follow-up is associated with increased selective neuronal damage. METHODS: We retrospectively analysed data from 76 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease with no ischaemic episodes on a follow-up of 6 months or more. All patients had measurements of the distribution of central benzodiazepine receptors twice using positron emission tomography and 11C-flumazenil. Using three-dimensional stereotactic surface projections, we quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the middle cerebral artery distribution and correlated these changes in the benzodiazepine receptors index with blood pressure values at follow-up examinations. RESULTS: The changes in the benzodiazepine receptor index during follow-up (mean 27±21 months) were negatively correlated with systolic blood pressure at follow-up. The relationship between changes in benzodiazepine receptor index and systolic blood pressure was different among patients with and without decreased cerebral blood flow at baseline (interaction, p<0.005). Larger increases in benzodiazepine receptor index (neuronal damage) were observed at lower systolic blood pressure levels in patients with decreased cerebral blood flow than in patients without such decreases. CONCLUSION: In patients without ischaemic stroke episodes at follow-up but with decreased cerebral blood flow due to arterial disease, low systolic blood pressure at follow-up may be associated with increased selective neuronal damage.

3-Aminobenzamide protects against cerebral artery injury and inflammation in rats with intracranial aneurysms.

This study aimed to investigate the treatment effects and molecular mechanism of 3-aminobenzamide (3-AB) on intracranial aneurysms (IA). The IA model was established in male Sprague-Dawley (SD) rats and sham group was set up without ligation. The rats were intraperitoneally injected with normal saline in sham and model control groups and 10 mg/kg, 20 mg/kg and 40 mg/kg 3-AB for low, middle and high 3-AB groups for 3 months, respectively. The rates in and blood pressures of caudal artery were measured and anterior cerebral artery and olfactory artery were stained with hematoxylin and eosin (HE) for morphology observation. Besides, the effects of 3-AB on inflammatory cells, macrophages, neutrophils and T cells, were evaluated using immunohistochemistry. Gene expressions of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65 were measured using qRT-PCR and the protein levels of TLR4, PARP-1 and p-p65 were evaluated using western blotting. Blood pressures of rats in 3-AB treatment groups were decreased in a dose-dependent manner. The damage of cerebral artery wall was alleviated and the inflammatory cells (macrophages, neutrophils and T cells) were reduced to some extent in 3-AB high-dose groups. The gene expression of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65, as well as the protein expression of TLR4, PARP-1 and p-p65 in 3-AB treatment groups were decreased in a dose-dependent manner (P < 0.01).3-AB exhibited therapeutic effects on IA through inhibiting the secretions of inflammatory cytokines and MMPs.

Reversible Dilation of Cerebral Macrovascular Changes in MELAS Episodes.

PURPOSE: To investigate the cerebral macrovascular changes as well as the relationship of large vessels and cerebral blood flow (CBF) in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) using magnetic resonance angiography (MRA) and arterial spin labeling (ASL) perfusion MR imaging (MRI). METHODS: A total of 20 patients diagnosed with MELAS (12 males, 8 females; mean age, 23.3 years) underwent conventional MRI, time-of-flight (TOF) MRA and three dimensional ASL. Follow-up scans were performed in 10 patients. The changes of cerebral arteries and branches on MRA images from both acute and recovery patients were independently evaluated by two radiologists. Lesion distribution and CBF were observed on the integrated maps of MRA and ASL. RESULTS: In 14 patients with clinical onsets, increased CBF was observed in all stroke-like lesions. Dilations of a single artery (four middle cerebral arteries, two posterior cerebral arteries) were found in six patients. Dilations of multiple arteries (two anterior cerebral arteries, seven middle cerebral arteries, six posterior cerebral arteries) were found in seven patients. Normal angiography was shown in one acute patient. Cortical terminal branches feeding the lesion areas were more obviously dilated than the main trunks. The dilated vessels returned to normal on follow-up scans concurrently with decreased CBF in nine patients who were resuscitated from episode attacks. Vasodilation was even seen in one preclinical patient who suffered a recurrent episode 50 days later. CONCLUSION: Reversible dilation of cerebral macrovascular changes could be a new feature of MELAS and a presumed reason for fluctuant CBF. It would shed new light on the mitochondrial angiopathy.

Chronic Dilatation of Superficial Temporal Artery and Middle Meningeal Artery Associated with Development of Collateral Circulation After Bypass Surgery for Moyamoya Angiopathy.

OBJECTIVES: Dilatation of the superficial temporal artery (STA) and middle meningeal artery (MMA) were occasionally observed after bypass surgery for moyamoya angiopathy. The purpose of this study was to examine the correlation between angiographic outcomes and magnetic resonance imaging (MRI), specifically focusing on the postoperative dilatation ratio of the STA (rSTA) and MMA (rMMA). METHODS: Fifty-six hemispheres in 36 consecutive patients who underwent revascularization for moyamoya angiopathy were evaluated. All patients underwent angiography and MRI before surgery and during the chronic phase. Angiographic outcomes were classified as good or poor according to the extent of the blood supply through direct or indirect bypass. The rSTA and rMMA was calculated in time-of-flight magnetic resonance angiography (MRA). The signal changes of ivy signs and flow voids in basal ganglia were also evaluated. RESULTS: Postoperative collaterals through direct and indirect bypass was good in 30 (53.6%) and 33 (58.9%) patients, respectively. The mean rSTA and rMMA were 36.04 ± 28.79% and 29.15 ± 22.01%, respectively. Ivy signs and flow voids were decreased in 9 (16.1%) and 26 (46.4%) patients, respectively. Univariate analyses demonstrated no significant correlation between the angiographic outcomes and postoperative signal changes on MRI. However, rSTA was significantly correlated with good collaterals through direct bypass (P = 0.04), whereas rMMA was significantly correlated with good collaterals through indirect bypass (P < 0.001). CONCLUSIONS: MRA may be an alternative to angiography. Both rSTA and rMMA estimated the development of collaterals after bypass surgery for moyamoya angiopathy.