Differential Vascular Pathophysiologic Types of Intracranial Atherosclerotic Stroke: A High-Resolution Wall Magnetic Resonance Imaging Study.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stroke (ICAS) has various stroke mechanisms, including branch occlusive disease (BOD), subcortical infarcts caused by parent arterial disease occluding the perforator's orifice, and non-BOD, infarcts beyond the subcortical area caused by artery-to-artery embolism. To test whether these 2 types of ICAS had different vascular pathophysiologies, we compared the high-resolution magnetic resonance imaging characteristics between BOD and non-BOD ICAS. METHODS: Eighty patients with acute infarcts caused by ICAS of proximal middle cerebral artery or basilar artery without carotid/cardiac embolic sources or nonatherosclerotic causes were enrolled (36 BOD and 44 non-BOD patients). The steno-occlusive intracranial artery at the maximal stenosis was analyzed for vascular remodeling and wall enhancement. RESULTS: BOD had distinct radiological features in terms of vascular morphology and enhancement. BOD showed a milder stenosis than non-BOD (P<0.001). Positive remodeling was more frequently observed in non-BOD than in BOD (P=0.005). Wall area index was also lower in BOD. Plaque enhancement was observed in all but one non-BOD patient and in one fourth of BOD patients (P=0.003). Although both types showed an eccentric enhancement, this enhancement was more frequently distributed in the BOD group on the side where the perforators arose. As the number of asymptomatic intracranial stenosis increased, the degree of stenosis (rho=0.513, P=0.003) increased in the BOD group, whereas enhanced plaque area (rho=0.343, P=0.030) increased in the non-BOD group. CONCLUSIONS: Our data indicate that BOD is a common and unique form of ICAS, distinct from non-BOD. These 2 types of ICAS have different vascular pathophysiologies in terms of vascular remodeling and plaque characteristics.

Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

BACKGROUND AND PURPOSE: Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. METHODS: Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. RESULTS: Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). CONCLUSIONS: Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth.

A novel magnetic resonance imaging approach to collateral flow imaging in ischemic stroke.

OBJECTIVE: Dedicated magnetic resonance (MR) imaging (MRI) sequences for evaluation of collaterals can be generated using MR perfusion (MRP) source data. We compared a novel collateral flow imaging technique with digital subtraction angiography (DSA) for determining collateral circulation in acute stroke and evaluated the ability of MR-based collateral flow maps to predict outcomes after recanalization therapy. METHODS: Consecutive patients who were candidates for endovascular treatment were enrolled. A collateral flow map derived from MRP source data was generated by manual or automatic postprocessing. Collateral grading based on the collateral flow map was performed and compared with grading based on DSA. Clinical and radiological outcomes were evaluated according to MR-based collateral grading and early reperfusion (ER) status. RESULTS: There was good correlation between MRI-based and DSA-based collateral grades (weighted κ-coefficient = 0.70). Collateral status and achievement of ER were the 2 main determinants of a favorable functional outcome and neurological improvement, in addition to infarct growth. Regardless of achievement of ER, better collaterals were significantly associated with a lower modified Rankin score at day 90 (p < 0.001 for trend in both ER(-) and ER(+) ). Most symptomatic intracranial hemorrhages occurred in patients with a poor collateral grade and ER(+) , whereas no patient with excellent collaterals suffered symptomatic intracranial hemorrhage or died. INTERPRETATION: MRI techniques to assess collaterals are rapidly being developed, and may provide insight into collateral perfusion. The combination of collateral images derived from pretreatment MRP source data and reperfusion status is a robust predictor of outcomes in acute ischemic stroke.

Eligibility and preference of new oral anticoagulants in patients with atrial fibrillation: comparison between patients with versus without stroke.

BACKGROUND AND PURPOSE: Recent randomized clinical trials (RCTs) have evaluated the benefit of new oral anticoagulants in reducing the risk of vascular events and bleeding complications in patients with atrial fibrillation (AF). However, abundant and strict enrollment criteria may limit the validity and applicability of results of RCTs to clinical practice. We estimated the eligibility for participation in RCTs of an unselected group of patients with AF. In addition, we compared features favoring new oral anticoagulant use between patients with versus without stroke. Randomized Evaluation of Long-Term Anticoagulation Therapy METHODS: We applied enrollment criteria of 4 RCTs (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) to 695 patients with AF taking warfarin, prospectively and consecutively collected at a university medical center; 500 patients with and 195 patients without stroke. Time in therapeutic range and bleeding risk scheme (anticoagulation and risk factors in atrial fibrillation) were also measured. RESULTS: The proportions of patients fulfilling the trial enrollment criteria varied, ranging from 39% to 72.8%, depending on the differences in indications/contraindications among studies and presence/absence of stroke. The main reasons for ineligibility for RCTs were hemorrhagic risk (anticoagulation and risk factors in atrial fibrillation [ATRIA] score) (10.8%-40.5%) and planned cardioversion (5.1%-7.7%) for nonstroke patients, and a low creatinine clearance (5.6%-9.2%) and higher risk of bleeding (15.2%-20.8%) for patients with stroke. When compared with nonstroke patients, patients with stroke showed a lower time in therapeutic range (54.4±42.8% versus 65.4±34.9%, especially with severe disability) and a high hemorrhagic risk (ATRIA score) (3.06±2.30 versus 2.18±2.16) (P<0.05 in both cases). CONCLUSIONS: Patients enrolled in RCTs are partly representative of patients with AF in clinical practice. When time in therapeutic range and bleeding tendency with warfarin use were considered, the use of new oral anticoagulants was preferred in patients with stroke than in nonstroke patients, but they were more likely to be excluded in RCTs.

High-resolution magnetic resonance wall imaging findings of Moyamoya disease.

BACKGROUND AND PURPOSE: Diagnosis of Moyamoya disease (MMD) is based on the characteristic angiographic findings. However, differentiating MMD from intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall imaging findings on high-resolution magnetic resonance imaging between MMD and ICAD. METHODS: High-resolution magnetic resonance imaging was performed on 32 patients with angiographically proven MMD and 16 patients with acute infarcts because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle cerebral artery were analyzed for wall enhancement and remodeling. RESULTS: Enhancement patterns and distribution were different. Most patients with MMD (90.6%) showed concentric enhancement on distal internal carotid arteries and middle cerebral arteries, whereas focal eccentric enhancement was observed on the symptomatic segment in ICAD. MMD was characterized by middle cerebral artery shrinkage; the remodeling index and wall area were lower in MMD than in ICAD (remodeling index, 0.19±0.11 versus 1.00±0.43; wall area, 0.32±0.22 versus 6.00±2.72; P<0.001). CONCLUSIONS: MMD was characterized by concentric enhancement on bilateral distal internal carotid arteries and shrinkage of middle cerebral artery, regardless of symptoms.

Is atrial fibrillation always a culprit of stroke in patients with atrial fibrillation plus stroke?

BACKGROUND: Some ischemic strokes in patients with atrial fibrillation (AF) are caused by noncardioembolic etiologies (AF-unrelated stroke), but not AF itself (AF-related stroke). However, most clinical trials on the risk of stroke in AF have not distinguished between these. We investigated the frequency and features of AF-unrelated versus AF-related strokes in patients with AF plus ischemic stroke. We hypothesized that certain clinical factors, including chronicity of AF, treatment at the time of stroke onset and echocardiographic findings, may help to discriminate between AF-related and AF-unrelated strokes. The mechanisms and antithrombotic medications at the time of stroke recurrence in the two groups were also examined. METHODS: Consecutive patients with ischemic stroke within 7 days of symptom onset and with AF were included. Patients were classified according to the previously published criteria. Clinical factors including CHADS2 and CHA2DS2-VASc scores and transthoracic echocardiographic (TTE) findings were evaluated. RESULTS: Of 522 patients, 424 (81.2%) were grouped as AF-related stroke and the remaining 90 (17.2%) were classified as AF-unrelated stroke. Among the patients with AF-unrelated stroke, 51 (9.8%) were categorized as possible large artery atherosclerosis and 38 (7.3%) as possible small artery occlusion; 1 patient (0.2%) was assigned to miscellaneous cause. The AF-related and AF-unrelated strokes had similar CHADS2 and CHA2DS2-VASc scores. However, compared to AF-unrelated stroke, AF-related stroke was independently associated with female sex (odds ratio, OR, 2.19; 95% confidence interval, CI, 1.18-4.05), sustained AF (OR, 2.09; 95% CI, 1.21-3.59), inadequate anticoagulation at stroke onset (OR, 3.21; 95% CI, 1.33-7.75) and left ventricular dysfunction on TTE (OR, 2.84; 95% CI, 1.40-5.74). We identified 26 patients who experienced 2 strokes during the study period. The initial stroke subtype was a strong predictor of the recurrent stroke mechanism (p < 0.001). Among 17 events of AF-related recurrent stroke in these subpopulation, only 2 strokes (11.8%) occurred in a setting of adequate anticoagulation, whereas 4 out of 9 patients (44.4%) who had AF-unrelated strokes at recurrence were sufficiently anticoagulated at the time of admission (p = 0.138). CONCLUSION: AF is not always a culprit of stroke in patients with AF plus ischemic stroke; approximately one sixth of these cases are unrelated to AF and have distinct characteristics compared to AF-related stroke. There are significant differences in terms of some clinical and TTE parameters between AF-related and AF-unrelated stroke. Future studies are warranted to optimize strategies for risk stratification, treatment and prevention of stroke in these patients.

Sulcal effacement on fluid attenuation inversion recovery magnetic resonance imaging in hyperacute stroke: association with collateral flow and clinical outcomes.

BACKGROUND AND PURPOSE: The clinical significance of sulcal effacement has been widely investigated in CT studies, but the results are controversial. In this study, we evaluated the presence of perisylvian sulcal effacement (PSE) on fluid attenuation inversion recovery MRI and hypothesized that PSE may be related to collateral flow status together with hyperintense vessels on fluid attenuation inversion recovery in hyperacute stroke. In addition, we investigated whether an association between PSE and clinical outcome could be found in these patients. METHODS: Consecutive patients with acute middle cerebral artery infarcts within 6 hours of symptom onset were included. All patients had internal carotid artery or middle cerebral artery occlusion and underwent MRI including FLAIR. The presence of PSE and hyperintense vessels on fluid attenuation inversion recovery and the collateral status and occurrence of early recanalization (ER) on conventional angiography were evaluated. RESULTS: Of 139 patients, 79 (56.8%) had PSE. Multivariate testing revealed PSE was independently associated with collateral status. The association between hyperintense vessels and collaterals was different depending on PSE. Compared to PSE-positive and ER-negative patients, PSE-negative and ER-negative patients (odds ratio, 4.11; 95% confidence interval, 1.12-15.17) and PSE-negative and ER-positive patients (odds ratio, 34.62; 95% confidence interval, 5.75-208.60), but not PSE-positive and ER-positive patients, were more likely to experience favorable clinical outcomes (modified Rankin Scale score ≤ 2 at 3 months). CONCLUSIONS: PSE is independently associated with collateral status in patients with acute middle cerebral artery stroke. Moreover, PSE in conjunction with recanalization status can predict clinical outcomes in these patients.

Characterization of the infarct pattern caused by vulnerable aortic arch atheroma: DWI and multidetector row CT study.

BACKGROUND: Aortic arch atheroma (AAA) has been accepted as a possible embolic source in patients with ischemic stroke, especially cryptogenic stroke. However, despite its well-known role as a risk factor for stroke, research focused on the mechanism or characteristics of stroke caused by AAA is insufficient. In this study, we aimed to evaluate clinical and radiological characteristics including lesion pattern on DWI in acute stroke patients associated with vulnerable AAA detected by multidetector row computed tomography (MDCT). METHODS: From September 2008 through May 2011, patients who presented with acute ischemic stroke and underwent MDCT were found in a prospective stroke registry. Patients without evident stroke etiology were included and classified by presence of vulnerable AAA. Vulnerable AAA was defined as (i) at least 6 mm thick adjacent to the aortic wall; (ii) ulcerated plaque, or (iii) soft plaque. Soft plaque was defined as the presence of clearly visualized area of hypoattenuation (<80 Hounsfield units) suggestive of thrombus. The patients without vulnerable AAA were classified as no/simple AAA group. The characteristics of diffusion-weighted MRI (DWI) lesions were analyzed in terms of the number and size of the lesions, and the involved vascular territories. RESULTS: A total of 63 cryptogenic stroke patients were included in this study. Vulnerable AAA was observed in 15 (23.8%) patients. The patients with vulnerable AAA were older than those with no/simple AAA (p = 0.026). DWI analysis revealed that the vulnerable AAA group had a greater chance of having multiple and small lesions in multiple vascular territories that were mainly located in cortical and border-zone regions than the no/simple AAA group. Multiple logistic regression analysis showed that age (odds ratio 1.17; 95% confidence interval 1.02-1.34) and multiple small lesions in multiple vascular territories (odds ratio 33.18; 95% confidence interval 4.26-258.45) were independently associated with vulnerable AAA. CONCLUSION: Vulnerable AAA is independently associated with a DWI pattern characterized by multiple small scattered lesions in multiple vascular territories in conjunction with age. It may help determine stroke mechanism quickly and easily, and provide more information about the pathomechanism of vulnerable AAA-related stroke.

Truncal ataxia from infarction involving the inferior olivary nucleus.

Truncal ataxia in medullary infarction may be caused by involvement of the lateral part of the medulla; however, truncal ataxia in infarction involving the inferior olivary nucleus (ION) has received comparatively little attention. We report a patient with truncal ataxia due to medial medullary infarction located in the ION. A lesion in the ION could produce a contralateral truncal ataxia due to increased inhibitory input to the contralesional vestibular nucleus from the contralesional flocculus.

Perfusion-weighted MRI as a predictor of clinical outcomes following medullary infarctions.

BACKGROUND: Perfusion-weighted imaging (PWI) is rarely used to evaluate cases of posterior circulation infarctions. We evaluated clinical outcomes, diffusion-weighted imaging (DWI) patterns and angiographic findings in patients experiencing medullary infarctions according to PWI results. METHODS: Data from consecutive patients with acute ischemic lesions primarily involving the medulla were analyzed. All patients underwent MRI including DWI, PWI and MR angiography. The patients were grouped according to the presence or absence of a perfusion delay in the medulla and/or inferior cerebellum. RESULTS: Among 35 patients, all but 1 had a PWI of interpretable quality. Of these 34 patients, 18 had a normal perfusion status, while 16 had perfusion defects in the medulla and/or inferior cerebellum. The abnormal PWI group had poor clinical outcomes at 7 days and 1 month after the onset of symptoms. There was no difference in DWI patterns between these 2 groups. The angiographic findings demonstrated that a stenosis of >or=50% or an occlusion of the ipsilesional vertebral artery was frequently observed in the abnormal PWI group (p = 0.001). Multivariate analysis revealed that abnormal PWI and DWI patterns were independently associated with poor early and late outcomes following medullary infarctions. CONCLUSIONS: PWI may be a feasible modality for assessing the perfusion status of the posterior circulation and predicting clinical outcomes following medullary infarctions.

Brain microangiopathy and macroangiopathy share common risk factors and biomarkers.

AIMS: Besides carotid or cardiac embolism, stroke can occur via microangiopathy (small arterial disease [SAD]) and macroangiopathy (intracranial atherosclerotic stroke [ICAS]) of the intracranial vasculature. There have been efforts to identify risk factors specific to microangiopathy and macroangiopathy, including vascular risk factors, and protein and genetic biomarkers. We hypothesized that despite the anatomic and pathophysiological differences between microvessels and macrovessels, microangiopathy and macroangiopathy share common risk factors during disease progression. METHODS: Among 714 patients with acute infarctions within middle cerebral artery territory, 126 with SAD and 116 with ICAS were included in this study. Subclinical microangiopathy (degree of leukoaraiosis) and macroangiopathy (number of tandem stenosis) was graded in each patient. Inflammatory biomarkers (C-reactive protein, E-selectin, and LpPLA2), endothelial dysfunction (asymmetric dimethylarginine, urinary albumin-to-creatinine ratio, endostatin, and homocysteine), atherogenesis (lipoprotein(a), adiponectin, and resistin), and renal function (creatinine clearance and estimated glomerular filtration rate) were assessed. RESULTS: Compared with the patients with isolated SAD, those with isolated ICAS were younger, were current smokers, and showed higher apoB levels (p < 0.05 in all cases). However, with the progression of subclinical microangiopathy, asymptomatic macroangiopathy worsened and vice versa. No significant differences in risk factors were observed between advanced SAD and ICAS. Decreased renal function was independently associated with progression of microangiopathy and macroangiopathy. Markers of endothelial dysfunction, but not the other markers, were significantly related to creatinine clearance level. CONCLUSIONS: Mild to moderate loss of renal function is strongly associated with both intracranial microangiopathy and macroangiopathy. Endothelial dysfunction may be associated with this relationship.

An Approach to Working Up Cases of Embolic Stroke of Undetermined Source.

BACKGROUND: From a therapeutic viewpoint, it is important to differentiate the underlying causes of embolism in patients with cryptogenic stroke, such as aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. We investigated the clinical and radiological characteristics of these 3 common causes of cryptogenic embolism to develop models for decision making in etiologic workups. METHODS AND RESULTS: A total of 321 consecutive patients with acute infarcts from cryptogenic embolism were included. Patients were divided into 3 groups-aortic arch atheroma (n=40), patent foramen ovale (n=153), and paroxysmal atrial fibrillation (n=128)-based on extensive cardiologic workups. We used a multinomial logistic regression analysis to detect the clinical and diffusion-weighted imaging factors associated with the probability of aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. Clinical and radiological features differed among the groups. The patent foramen ovale group had a healthy vascular risk factor profile and showed posterior circulation involvement compared with other groups (P<0.01). In contrast, paroxysmal atrial fibrillation-related strokes had higher initial National Institutes of Health Stroke Scale (NIHSS) scores and larger lesions than the other groups (P<0.001). The aortic arch atheroma group had clinical features similar to those of the paroxysmal atrial fibrillation group but showed small lesions scattered in multiple vascular territories (P<0.001). Multivariate regression analysis revealed that age, initial NIHSS score, lesion size (≥20 mm), multiple (≥3) lesions, and involvement of posterior circulation or multiple vascular territories differentiated the 3 groups (pseudo, R(2)=0.656). The prediction ability of this model was validated in the external validation cohort (n=117, area under the curve 0.78). CONCLUSIONS: Our data indicate that patients with cryptogenic embolic stroke show distinct clinical and radiological features depending on the underlying causes.

Association of Left Atrial Enlargement with Cortical Infarction in Subjects with Patent Foramen Ovale.

BACKGROUND AND PURPOSE: Left atrial dysfunction has been reported in patients with patent foramen ovale (PFO). Here we investigated the role of left atrial dysfunction in the development of embolic stroke in patients with PFO. METHODS: We identified consecutive patients with embolic stroke of undetermined sources except for PFO (PFO+ESUS). Healthy subjects with PFO served as controls (PFO+control). A stratified analysis by 10-year age group and an age- and sex- matching analysis were performed to compare echocardiographic markers between groups. In the PFO+ESUS group, infarct patterns of PFO-related stroke were determined (cortical vs. cortico-subcortical) and analyzed in correlation with left atrial function parameters. RESULTS: A total of 118 patients and 231 controls were included. The left atrial volume indices (LAVIs) of the PFO+ESUS patients were higher than those of the PFO+controls in age groups of 40-49, 50-59, and 60-69 years (P<0.001, P=0.003, and P=0.027, respectively), and in the age- and sex-matched analysis (P=0.001). In the PFO+ESUS patients, a higher (>28 mL/m2) LAVI was more associated with the cortical infarct pattern (P=0.043 for an acute infarction and P=0.024 for a chronic infarction, both adjusted for age and shunt amount). The degree of right-to-left shunting was not associated with infarct patterns, but with the posterior location of acute infarcts (P=0.028). CONCLUSIONS: Left atrial enlargement was associated with embolic stroke in subjects with PFO. Left atrial physiology might contribute to the development of PFO-related stroke and need to be taken into consideration for optimal prevention of PFO-related stroke.

Patent Foramen Ovale and Stroke-Current Status.

Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.

Comparison of Enoxaparin and Warfarin for Secondary Prevention of Cancer-Associated Stroke.

Background. The aim of this study was to determine which anticoagulant is superior for secondary prevention of cancer-associated stroke, using changes in D-dimer levels as a biomarker for recurrent thromboembolic events. Methods. We conducted a retrospective, single center observational study including patients with cancer-associated stroke who were treated with either enoxaparin or warfarin. Blood samples for measuring the initial and follow-up D-dimer levels were collected at admission and a median of 8 days after admission, respectively. Multiple logistic regression analysis was conducted to evaluate the factors that influenced D-dimer levels after treatment. Results. Although the initial D-dimer levels did not differ between the two groups, the follow-up levels were dramatically decreased in patients treated with enoxaparin, while they did not change with use of warfarin (3.88 µg/mL versus 17.42 µg/mL, p = 0.026). On multiple logistic regression analysis, use of warfarin (OR 12.95; p = 0.001) and the presence of systemic metastasis (OR 18.73; p = 0.017) were independently associated with elevated D-dimer levels (≥10 µg/mL) after treatment. Conclusion. In cancer-associated stroke patients, treatment with enoxaparin may be more effective than treatment with warfarin for lowering the D-dimer levels. Future prospective studies are warranted to show that enoxaparin is better than warfarin for secondary prevention in cancer-associated stroke.

Adult Moyamoya Disease: A Burden of Intracranial Stenosis in East Asians?

BACKGROUND: Both Moyamoya disease (MMD) and intracranial atherosclerotic stenosis (ICAS) are more prevalent in Asians than in Westerners. We hypothesized that a substantial proportion of patients with adult-onset MMD were misclassified as having ICAS, which may in part explain the high prevalence of intracranial atherosclerotic stroke in Asians. METHOD: We analyzed 352 consecutive patients with ischemic events within the MCA distribution and relevant intracranial arterial stenosis, but no demonstrable carotid or cardiac embolism sources. Conventional angiography was performed in 249 (70.7%) patients, and the remains underwent MRA. The occurrence of the c.14429G>A (p.Arg4810Lys) variant in ring finger protein 213 (RNF213) was analyzed. This gene was recently identified as a susceptibility gene for MMD in East Asians. RESULTS: The p.Arg4810Lys variant was observed in half of patients with intracranial stenosis (176 of 352, 50.0%), in no healthy control subjects (n = 51), and in 3.2% of stroke control subjects (4 of 124 patients with other etiologies). The presence of basal collaterals, bilateral involvement on angiography, and absence of diabetes were independently associated with the presence of the RNF213 variant. Among 131 patients who met all three diagnostic criteria and were diagnosed with MMD, three-fourths (75.6%) had this variant. However, a significant proportion of patients who met two criteria (57.7%), one criterion (28.6%), or no criteria (20.0%) also had this variant. Some of them developed typical angiographic findings of MMD on follow-up angiography. CONCLUSIONS: Careful consideration of MMD is needed when diagnosing ICAS because differential therapeutic strategies are required for these diseases and due to the limitations of the current diagnostic criteria for MMD.

Antioxidant effects of statins in patients with atherosclerotic cerebrovascular disease.

BACKGROUND AND PURPOSE: Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropic and low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that high-dose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke after statin use. This study evaluated changes in oxidative stress markers after short-term use of a high-dose statin in patients with atherosclerotic stroke. METHODS: Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and 1 month after dosing, and the serum levels of four oxidative stress markers-malondialdehyde (MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-were evaluated to determine the oxidation of MDA and lipids, proteins, and DNA, respectively, at both of those time points. RESULTS: The baseline levels and the degrees of reduction after statin use differed among the oxidative stress markers measured. MDA and PCO levels were associated with infarct volumes on diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin use decreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While the reduction in MDA levels after statin use was not associated with changes in cholesterol, that in oxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05). CONCLUSIONS: The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidative stress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidation via lipid-lowering-dependent and -independent mechanisms, but not against protein or DNA oxidation in atherosclerotic stroke patients.

Differential risk factors for lacunar stroke depending on the MRI (white and red) subtypes of microangiopathy.

BACKGROUND: Leukoaraiosis and cerebral microbleeds (CMB), which represent cerebral microangiopathy, commonly coexist in patients with acute lacunar stroke. Since they may have different impacts on stroke prognosis and treatment, it is important to know the factors associated with leukoaraiosis-predominant vs. CMB-predominant microangiopathies. METHODS: We prospectively recruited 226 patients with acute lacunar infarction and divided them into four groups according to the Fazekas' score and the presence of CMB: mild, red (predominant CMB), white (predominant leukoaraiosis) and severe microangiopathy groups. For comparison, we also evaluated 50 patients with intracerebral hemorrhage (ICH). We evaluated the clinical and laboratory findings of microangiopathy subtypes in patients with acute lacunar stroke and then compared them with those of primary ICH. RESULTS: The risk factor profile was different among the groups. Patients with acute lacunar infarct but mild microangiopathy were younger, predominantly male, less hypertensive, and more frequently had smoking and heavy alcohol habits than other groups. The risk factor profile of red microangiopathy was similar to that of ICH but differed from that of white microangiopathy. The subjects in the white microangiopathy group were older and more frequently had diabetes than those in the red microangiopathy or ICH group. After adjustments for other factors, age [odds ratio (OR) 1.13; 95% confidence interval (CI) 1.08-1.18; p<0.001] and diabetes (OR 2.28; 95% CI 1.02-5.13; p = 0.045) were independently associated with white microangiopathy, and age (OR 1.05; 95% CI 1.01-1.08; p = 0.010) was independent predictor for red microangiopathy compared to mild microangiopathy. CONCLUSION: Patients with acute lacunar infarction have a different risk factor profile depending on microangiopathic findings. Our results indicate that diabetes may be an one of determinants of white (leukoaraiosis-predominant) microangiopathy, whereas smoking and alcohol habits in relatively young people may be a determinants of mild microangiopahic changes in patients with lacunar infarction.

Dual therapy with cidofovir and mirtazapine for progressive multifocal leukoencephalopathy in a sarcoidosis patient.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease caused by JC virus (JCV) reactivation in immunocompromised patients. The disease course of PML is often progressive, fatal and at present, there are few reports on successful treatment outcomes. CASE REPORT: A 45-year-old man with systemic sarcoidosis presented with rapidly progressive dementia and right hemiparesis. The patient was diagnosed with PML as confirmed via brain biopsy and JCV PCR. With a combination treatment of cidofovir and mirtazapine, there was significant improvement of neurological symptoms without measurable functional deficit. CONCLUSION: This case suggests that dual therapy with cidofovir and mirtazapine might be an effective treatment option in PML patients with sarcoidosis.