Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Stroke recurrence patterns are predicted by the subtypes and mechanisms of the past, non-cardiogenic stroke.

BACKGROUND AND PURPOSE: The association between past stroke subtypes and recurrent stroke subtypes in non-cardiogenic stroke remains unknown. METHODS: Patients with ischaemic stroke who had a past history of large-artery disease (LAD) or small-artery disease (SAD) subtypes were assessed. LAD was subdivided into intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS). LAD stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombotic occlusion and local branch occlusion, while SAD was subdivided into lacunar infarction (LI) and branch atheromatous disease (BAD) on the basis of magnetic resonance imaging findings. The relationship between past and current strokes was analyzed. RESULTS: Among the 202 patients enrolled, the LAD group (n = 111) had 64 and 47 patients with ICAS and ECAS, and the SAD group (n = 91) had 63 and 28 patients with LI and BAD, respectively, at the time of past stroke. Patients with LAD developed LAD-associated strokes most often (n = 99, 89.2%), and patients with SAD developed SAD most often (n = 69, 75.8%; P < 0.001). Patients with ICAS were more likely to develop ICAS later (n = 46, 79.3%), whereas those with ECAS developed ECAS more often (n = 31, 75.6%; P < 0.001). Patients with ICAS presenting with artery-to-artery embolism more often developed artery-to-artery embolism later (n = 26, 72.2%), whereas those with local branch occlusion developed recurrent local branch occlusion most often (n = 10, 66.7%, P = 0.005). In the SAD group, patients with BAD developed LAD more frequently than the LI group (n = 11, 39.3% vs. n = 9, 14.3%, P = 0.022). CONCLUSIONS: The subtypes and mechanisms of recurrent stroke are significantly influenced by those of the past stroke.

Paradoxical embolism as a cause of silent brain infarctions in healthy subjects: the ICONS study (Identification of the Cause of Silent Cerebral Infarction in Healthy Subjects).

BACKGROUND: In healthy elderly people, silent brain infarctions (SBIs) have been recognized as common lesions. In this study, we evaluated the association between SBI located outside the perforating artery territory (PAT) and paradoxical embolism detected by agitated saline transcranial Doppler (TCD) monitoring in healthy subjects. METHODS: This was a prospective observational study undertaken by a university health promotion center for healthy subjects and by a university stroke center for acute stroke patients. We defined SBI as evidence on fluid-attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) of one or more infarcts, without history of corresponding stroke or transient ischaemic attack. We also evaluated in all subjects the neuroimaging indicator of microangiopathy leukoaraiosis (LA). This study is registered with ClinicalTrials.gov, number NCT01429948. RESULTS: Amongst 1103 consecutive healthy adults who underwent MRI, 347 (31%) had one or more SBIs located outside the PAT, suggesting embolism. Amongst them, 253 subjects underwent agitated saline TCD monitoring and 128 (51%) had right-to-left shunts (RLS). The prevalence of RLS was similar to cryptogenic embolic stroke (62.0%, P = 0.056), but higher than in patients with other stroke subtypes (36.2%, P = 0.021). Amongst subjects with SBI, absence of LA was the only factor associated with RLS (OR 1.78; 95% CI 1.01-3.14; P = 0.046). CONCLUSION: Our results suggest that paradoxical embolism may play an important role in the development of SBI outside the PAT in apparently healthy adults.

Routine cardiac evaluation in patients with ischaemic stroke and absence of known atrial fibrillation or coronary heart disease: transthoracic echocardiography vs. multidetector cardiac computed tomography.

BACKGROUND AND PURPOSE: Cardiac evaluation is routinely conducted in patients with ischaemic stroke because embolisms originating from the heart are an important cause of stroke. We compared the prevalence of cardioaortic sources of cerebral embolism (CSCE) in patients with ischaemic stroke detected by transthoracic echocardiography (TTE) and/or multidetector cardiac computed tomography (MDCT). Additionaly, we investigated the frequency and severity of asymptomatic coronary artery disease (CAD) in patients who underwent MDCT. METHODS: We prospectively recruited patients with non-atrial fibrillation-related stroke who had no history of cardiac disease. Patients underwent cardiac evaluation using TTE alone (N=243, during the early phase of this study--TTE period), TTE and MDCT (N=62, midphase--transitional period) and MDCT alone (N=138, late phase--MDCT period). CSCE were defined according to the original and revised TOAST classifications. CAD was defined as 50% or more stenosis of the coronary artery. RESULTS: Patients' characteristics did not differ amongst groups; however, CSCE were more frequently detected in the MDCT period than in the TTE period (18.1% vs. 6.6%, P<0.001). In the transitional period, there were 16 patients (25.8%) who were found to be CSCE by MDCT but not TTE, whilst three patients (4.8%) were found to be CSCE by TTE but not MDCT (P=0.004). Amongst the patients who underwent MDCT, 72 (36.0%) had asymptomatic CAD, invasive coronary angiography was needed in 21 (10.5%) and 10 (5.0%) patients finally underwent coronary intervention. CONCLUSION: Multidetector cardiac computed tomography proved to be complementary to TTE for the identification of CSCE and can detect asymptomatic CAD, one of the major causes of vascular death in patients with stroke, in patients with non-atrial fibrillation-related stroke.

Characteristics of stroke mechanisms in patients with medullary infarction.

BACKGROUND: Few studies have focused on the mechanisms underlying medullary infarctions. Our aim in this study was to investigate stroke mechanisms in patients with medullary infarctions and to determine the clinical, radiological and laboratory characteristics of these patients with different underlying stroke etiologies. METHODS: Consecutive patients with medullary infarction were analysed. Stroke mechanisms were classified as large artery disease (LAD), cardiogenic embolism (CE), small vessel disease (SVD), arterial dissection or undetermined etiology. Clinical, radiological and laboratory factors were analysed according to the location of the lesion and stroke mechanisms. RESULTS: A total of 77 patients were enrolled in this study. Amongst them, 53 (68.8%) patients had lateral medullary infarction (LMI), 22 (28.6%) had medial medullary infarction (MMI), and the remaining 2 (2.6%) had hemimedullary infarction. In both LMI and MMI patients, LAD was the most frequently encountered stroke mechanism. Arterial dissection was the second most common cause followed by SVD and CE in patients with LMI, whereas SVD was more frequently observed (P < 0.001) and dissection and CE were less prevalent (P < 0.001 and P = 0.024, respectively) in MMI than in LMI. Regarding differences amongst stroke etiologies, patients with dissection were younger and had a significantly lower incidence of metabolic syndrome (P = 0.002 and P = 0.009, respectively) than patients with LAD and SVD. Patients in the LAD (19/34, 60%) and dissection groups (12/14, 75%) had abnormal perfusion-weighted MRI (PWI) findings, whereas all patients with SVD (9/9) had normal PWI findings (P < 0.001). CONCLUSIONS: Stroke mechanisms in medullary infarction differ between LMI and MMI. Clinical and radiological characteristics, especially PWI features, are helpful in discriminating the etiologies of stroke in these patients.

Identification of oxidized serum albumin in the cerebrospinal fluid of ischaemic stroke patients.

BACKGROUND AND PURPOSE: Extensive evidence has shown that oxidative stress mediates neuronal death in animal models of hypoxic-ischaemia. Brain biomarkers of oxidative stress need to be identified in order to better understand and treat brain damage in human stroke patients. The present study was conducted to identify potential target proteins of oxidative stress in the cerebrospinal fluid (CSF) of stroke patients with acute ischaemic brain injury. METHODS: We performed two-dimensional polyacrylamide gel electrophoresis to separate protein samples obtained from the CSF of control and stroke patients. To determine protein oxidation levels, oxyblot was then used to detect protein carbonyls that were determined by formation of a stable 2,4-dinitrophenylhydrazine (DNP) product using an anti-DNP antibody. RESULTS: We found that oxidation of serum albumin was increased in the CSF from stroke patients as well as rats who underwent permanent middle cerebral artery occlusion (6.5%, 23%, respectively). In stroke patients, oxidized albumin levels correlated to neurologic indications. CONCLUSIONS: The present study suggests that oxidized albumin in CSF can be utilized as an oxidative stress marker in human stroke patients.

Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts.

OBJECTIVES: The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction. METHODS: Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The "dominant" VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature. RESULTS: The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98). CONCLUSIONS: Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts.

Impact of posterior communicating artery on basilar artery steno-occlusive disease.

BACKGROUND: Acute brainstem infarction with basilar artery (BA) occlusive disease is the most fatal type of all ischaemic strokes. This report investigates the prognostic impact of the posterior communicating artery (PcoA) and whether its anatomy is a safeguard or not. METHODS: Consecutive patients who had acute brainstem infarction with at least 50% stenosis of BA upon CT angiography (CTA) were studied. The configuration of PcoA was divided into two groups upon CTA: "textbook" group (invisible PcoA with good P1 and P2 segment) and "fetal-variant of PcoA" group (only visible PcoA with absent P1 segment). Baseline demographics, radiological findings and stroke mechanisms were analysed. A multiple regression analysis was performed to predict clinical outcome at 30 days (modified Rankin disability Scale (mRS

Impact of collateral flow on tissue fate in acute ischaemic stroke.

BACKGROUND: Collaterals may sustain penumbra prior to recanalisation yet the influence of baseline collateral flow on infarct growth following endovascular therapy remains unknown. METHODS: Consecutive patients underwent serial diffusion and perfusion MRI before and after endovascular therapy for acute cerebral ischaemia. We assessed the relationship between MRI diffusion and perfusion lesion indices, angiographic collateral grade and infarct growth. Tmax perfusion lesion maps were generated and diffusion-perfusion mismatch regions were divided into Tmax >or=4 s (severe delay) and Tmax >or=2 but <4 s (mild delay). RESULTS: Among 44 patients, collateral grade was poor in 7 (15.9%), intermediate in 20 (45.5%) and good in 17 (38.6%) patients. Although diffusion-perfusion mismatch volume was not different depending on the collateral grade, patients with good collaterals had larger areas of milder perfusion delay than those with poor collaterals (p = 0.005). Among 32 patients who underwent day 3-5 post-treatment MRIs, the degree of pretreatment collateral circulation (r = -0.476, p = 0.006) and volume of diffusion-perfusion mismatch (r = 0.371, p = 0.037) were correlated with infarct growth. Greatest infarct growth occurred in patients with both non-recanalisation and poor collaterals. Multiple regression analysis revealed that pretreatment collateral grade was independently associated with infarct growth. CONCLUSION: Our data suggest that angiographic collateral grade and penumbral volume interactively shape tissue fate in patients undergoing endovascular recanalisation therapy. These angiographic and MRI parameters provide complementary information about residual blood flow that may help guide treatment decision making in acute cerebral ischaemia.

Risk Factors.

Studies investigating risk factors for intracranial atherosclerosis (ICAS) have been infrequent. However, due to recent availability of non-invasive vascular imaging techniques that can assess intracranial cerebral arteries, there are a growing number of studies on risk factors for ICAS. Conventional vascular risk factors such as hypertension, diabetes, hypercholesterolemia and cigarette smoking are risk factors for ICAS. However, it remains uncertain whether there is a difference in risk factors between ICAS and extracranial atherosclerosis (ECAS). It also remains unclear why ICAS is more common in Asians and Blacks than in Caucasians. Although we reviewed available evidences on these differences, the review was limited because studies were heterogeneous in the definition of risk factors, diagnostic method, and characteristics of study subjects (hospitalized vs. community) or cerebral vessels (symptomatic vs. asymptomatic). Nevertheless, it seems that hypercholesterolemia is more closely associated with ECAS than ICAS. The difference in hypercholesterolemia prevalence is one of the main reasons for racial differences in the location of cerebral atherosclerosis. Intracranial arteries contain higher antioxidant level than extracranial arteries and may be more vulnerable to risk factors that deplete antioxidants (e.g., metabolic syndrome and diabetes mellitus). Intracranial arteries may be more vulnerable to factors associated with hemodynamic stress (e.g., advanced, salt-retaining hypertension and arterial tortuosity) because of a smaller diameter, thinner media and adventitia, and fewer elastic medial fibers than extracranial arteries. Additionally, non-atherosclerotic arterial diseases (e.g., moyamoya disease) that commonly occur in the intracranial arteries of East Asians may contaminate the reports of ICAS cases. Various genes, including RNF 213, might also explain racial differences in atherosclerotic location. Prospective, well-designed risk factor and genetic studies should be performed in a homogeneous group of patients with diverse ethnicities. These efforts are essential in the prevention of atherosclerotic diseases based on adequate knowledge of the risk factors and pathogenesis.

Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells.

Although estrogen is known to exert beneficial effects on Alzheimer's disease, its underlying cellular mechanisms have not been clear. In this study we investigated whether or not neuroprotective effects of estrogen are mediated by estrogen receptors (ERs). Treatment of estrogen (1.8 nM) reduced beta-amyloid (Abeta)-induced death of ER-expressing W4 cells. This effect of estrogen was blocked by a specific ER blocker ICI 182,780. When estrogen was treated to HT22 cells, which lack functional ERs, Abeta-induced cell death was not affected. Transfection of HT22 cells with human ERalpha, but not ERbeta, restored protective action of estrogen against Abeta. Hoechst staining revealed that estrogen protected ERalpha-expressing cells by blocking Abeta-induced apoptosis. These results indicate that estrogen blocks Abeta-induced cell death via ERalpha-dependent pathways.

Pure motor hemiplegia with conjugate lateral gaze palsy in pontine lacunar infarction.

The combination of pure motor hemiplegia and horizontal gaze palsy is a rare but identifiable lacunar syndrome. Among horizontal gaze palsies, one-and-a-half syndrome and abducens nerve palsy are reported to be associated with pure motor hemiplegia in pontine lacunar infarction. Although conjugate lateral gaze palsy is also hypothesized, pure motor hemiplegia with conjugate lateral gaze palsy has never been reported. We present a 75-year-old man who showed right hemiparesis and impaired left horizontal conjugate eyeball movement. Both the findings of the brain CT scan and those of the MRI study were consistent with a small infarction in the left midpontine tegmentum. Magnetic resonance angiography revealed no stenotic narrowing of the vertebrobasilar artery. Radiological findings suggested that pure motor hemiplegia with conjugate lateral gaze palsy, in our patient, might have been produced by the occlusion of a single penetrating branch of the basilar artery.

Sympathetic skin response and cardiovascular autonomic function tests in Parkinson's disease.

Autonomic dysfunction commonly occurs in Parkinson's disease, but the pathogenesis of autonomic dysregulation remains uncertain. Autonomic functions regulating the cardiovascular system have been investigated in Parkinson's disease, but those involving the extremities has not been well demonstrated. To compare autonomic dysfunctions of the cardiovascular system with those of the extremities, we performed sympathetic skin response (SSR) and cardiovascular autonomic function tests (CAFT)-30 : 15 ratio, E : I ratio, Valsalva ratio, isometric exercise test (IET)--in 37 patients with Parkinson's disease and 33 age- and sex-matched healthy controls. The patients were asked to stop antiparkinsonian medications for at least 12 hours prior to the tests. SSR was measured at the right hand and foot after electrical stimulation of the right median and posterior tibial nerves. Absent SSR at either one or both extremities and CAFT beyond normal ranges were regarded as abnormal. Abnormal SSR was observed in 59% of patients, while abnormal CAFT were found in the range of 32%-81%. Patients with abnormal SSR showed more frequent and severe CAFT abnormalities than did patients with normal SSR. Among the CAFT, IET was well correlated with the SSR. The results suggest that parkinsonian sympathetic dysfunction involving either the cardiovascular system or the extremities may have the same pathophysiology.

Branch occlusive disease: clinical and magnetic resonance angiography findings.

BACKGROUND: We evaluated the clinicoradiologic characteristics of patients with branch occlusive disease (BOD)-type intracranial atherosclerotic stroke (ICAS) compared with those of patients with non-BOD-type ICAS or with small artery disease (SAD). METHODS: We analyzed 201 consecutive patients with acute infarcts within the middle cerebral artery (MCA) distribution but no demonstrable carotid or cardiac embolism sources. According to the diffusion-weighted imaging (DWI) distribution and the presence of ipsilateral MCA stenosis, of any degree, on magnetic resonance angiography (3-T MRI), we divided patients into 3 groups: 1) BOD: subcortical infarcts with MCA stenosis (n = 46); 2) non-BOD: infarcts beyond the subcortical area with MCA stenosis (n = 52); and 3) SAD (n = 103). We compared risk factors, degree of stenoses and distribution, and radiologic features of microangiopathy (leukoaraiosis and cerebral microbleeds) among the groups. RESULTS: Risk factor profiles were similar among the groups, except that hypertension and current smoking were more prevalent in the non-BOD than in the BOD group (p = 0.032 and 0.045). The relevant MCA had more severe and focal stenosis in the non-BOD than in the BOD group (stenosis of ≥70%; 76.9% vs 28.3%; p < 0.001), but the degree of nonrelevant stenosis was similar across the groups. Although clinical features, DWI lesion patterns, and microangiopathy findings were similar between the BOD and SAD groups, nonrelevant stenosis was more prevalent in the BOD than in the SAD group (p < 0.01). CONCLUSIONS: BOD is prevalent (47% of ICAS) and shares common characteristics with non-BOD-type ICAS, although its clinicoradiologic features may resemble those of SAD. The morphologic characteristics of stenosis and risk factors may associate with a stroke phenotype in patients with ICAS.

Elevated serum lipoprotein(a) as a potential predictor for combined intracranial and extracranial artery stenosis in patients with ischemic stroke.

OBJECTIVES: Despite compelling evidence of lipoprotein(a) [Lp(a)] as a risk factor for ischemic stroke, its underlying mechanism remains unclear. Our aim is to investigate whether serum Lp(a) level is associated with the extent and location of cerebral steno-occlusive lesions, and with large artery atherosclerotic (LAA) stroke in Korean patients. METHODS: We analyzed data prospectively collected over a 3-year period on consecutive patients with stroke or TIA. Based on an angiographic study, a total of 1012 patients were classified into four subtypes: non-cerebral stenosis (n=654), intracranial stenosis (n=198), extracranial carotid stenosis (n=86), and combined intracranial and extracranial carotid stenosis (n=74). Independent associations of Lp(a) levels with the extent and location of cerebral stenosis were evaluated, and Lp(a) levels of subtypes by the TOAST criteria were compared. RESULTS: Lp(a) levels of LAA stroke were significantly higher than those of the other four stroke mechanisms. Patients with more advanced intracranial (p=0.001) and extracranial carotid stenoses (p=0.001) tended to have higher Lp(a) levels. In multiple regression analysis, the third Lp(a) quartile was the strongest risk factor for isolated intracranial (OR 3.36, 95% CI 1.77-6.37) or extracranial stenosis (OR 4.82, 95% CI 1.96-11.88), whereas the fourth Lp(a) quartile was the most powerful predictor for combined intracranial and extracranial carotid stenosis (OR 4.98, 95% CI 1.92-12.91). CONCLUSIONS: Our results indicate that greatly elevated Lp(a) levels are associated with LAA stroke and extensive burden of cervicocerebral steno-occlusive lesions, which might offer indirect evidence of proatherothrombogenic role of Lp(a) in ischemic stroke.

Association of serum lipid indices with large artery atherosclerotic stroke.

BACKGROUND: Low-density lipoprotein cholesterol (LDL) is the primary lipid target for vascular risk reduction in stroke patients, but emerging data suggest that other lipid indices may better predict vascular hazard. We evaluated the relationship between several measures of the classically obtained serum lipid panel and the occurrence of large artery atherosclerotic stroke. METHODS: Data prospectively collected over a 4-year period on subjects admitted with ischemic stroke or TIA to a university medical center were analyzed. Independent associations of fasting serum lipid indices with large artery atherosclerotic (LAA) stroke mechanism were evaluated. RESULTS: Of 1,049 patients, 247 (23.5%) were classified with LAA, 224 (21.4%) were classified with small vessel disease (SVD), and 578 (55%) were non-LAA, non-SVD subtype. Lipid levels were similar between LAA and SVD patients. Total cholesterol, triglycerides, LDL, non-high-density lipoprotein cholesterol (HDL), and triglyceride:HDL ratio were significantly higher in LAA vs non-LAA, non-SVD patients. After adjustment for age, hypertension, diabetes, smoking, body mass index, and premorbid statin use, significant odds ratios (ORs) for LAA compared with all other ischemic stroke subtypes for patients in the uppermost lipid quartiles (vs lowest) were triglycerides (OR 2.69, 95% CI 1.44 to 5.02) and non-HDL (OR 2.39, 95% CI 1.40 to 4.11). LDL was not associated with LAA. CONCLUSIONS: Compared with all other ischemic stroke subtypes, elevated levels of serum triglycerides and non-high-density lipoprotein, but not low-density lipoprotein (LDL), are associated with large artery atherosclerotic stroke. These non-LDL lipid measures may have utility in delineating atherosclerotic stroke risk.

Determinants of the distribution and severity of hypoperfusion in patients with ischemic stroke.

BACKGROUND: In acute cerebral ischemia, two variables characterize the extent of hypoperfusion: the volume of hypoperfused tissue and the intensity of hypoperfusion within these regions. We evaluated the determinants of the intensity of hypoperfusion within oligemic regions among patients who were eligible for recanalization therapy for acute ischemic stroke. METHODS: We analyzed data, including pretreatment diffusion-weighted imaging (DWI) and perfusion-weighted imaging, on 119 patients with acute middle cerebral artery infarctions. The intensity of hypoperfusion within oligemic regions was characterized by the hypoperfusion intensity ratio (HIR), defined as the volume of tissue with severe hypoperfusion (Tmax > or = 8 seconds) divided by the volume of tissue with any hypoperfusion (Tmax > or = 2 seconds). Based on the DWI data, we divided the patients into four stroke phenotypes: large cortical, small (< 1 cm diameter) cortical, border-zone, and deep pattern. RESULTS: The mean (SD) volume of severe hypoperfusion was 54.6 (52.5) mL, and that of any hypoperfusion was 140.8 (81.3) mL. The HIR ranged widely, from 0.002 to 0.974, with a median of 0.35 (interquartile range 0.13-0.60). The volume of any hypoperfusion did not predict the intensity of hypoperfusion within the affected region (r = 0.10, p = 0.284). Angiographic collateral flow grade was associated with HIRs (p value for trend = 0.019) and differed among DWI lesion patterns. In multivariate analysis, diastolic pressure on admission (odds ratio 0.959, 95% CI 0.922-0.998) and DWI pattern of deep infarcts (odds ratio 18.004 compared with large cortical pattern, 95% CI 1.855-173.807) were independently associated with a low HIR. CONCLUSIONS: The intensity of hypoperfusion within an oligemic field is largely independent of the size of the oligemia region. Predictors of lesser intensity of hypoperfusion are lower diastolic blood pressure and presence of a deep diffusion-weighted imaging lesion pattern.

Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy.

We evaluated the feasibility and safety of therapy with mesenchymal stem cells (MSCs) through consecutively intra-arterial and three repeated intravenous injections and compared the long-term prognosis between MSC-treated (n=11) and control multiple system atrophy (MSA) patients (n=18). The MSC-treated patients showed significantly greater improvement on the unified MSA rating scale (UMSARS) than the control patients at all visits throughout the 12-month study period. Orthostasis in UMSARS I items and cerebellar dysfunction-related items of UMSARS II items were significantly different in favor of MSC treatment compared to controls. Serial positron emission tomography scan in the MSC-treated group showed that increased fluorodeoxyglucose uptake from baseline was noted in cerebellum and frontal white matters. No serious adverse effects related to MSC therapy occurred. This study demonstrated that MSC therapy in patients with MSA was safe and delayed the progression of neurological deficits with achievement of functional improvement in the follow-up period.

Adiponectin levels in patients with intracranial atherosclerosis.

BACKGROUND: Adiponectin is a protein secreted by adipose cells that improves insulin sensitivity and possesses antiatherogenic properties. In this study, we investigated the relationship between adiponectin levels and ischemic stroke subtype. METHODS: Using clinical, imaging, and laboratory data, 231 consecutive patients admitted to a university medical center over a 2-year period with acute cerebral infarcts were categorized into four subtypes: intracranial atherosclerosis (n = 67), extracranial atherosclerosis (n = 61), small arterial occlusion (n = 63), and cardioembolic (n = 40). Clinical features, risk factors including the presence of metabolic syndrome, and levels of s-adiponectin were compared between groups. RESULTS: Patients with more severe metabolic abnormalities were more likely to have lower s-adiponectin levels (p = 0.002). S-adiponectin levels differed by stroke subtype: highest in the cardioembolic group and lowest in the intracranial atherosclerosis group (8.42 +/- 5.07 vs 5.60 +/- 2.79 microg/mL, p = 0.01). Extracranial atherosclerosis (6.45 +/- 4.10 microg/mL) and small arterial occlusion (6.07 +/- 3.44 microg/mL) groups were intermediate. Patients with advanced intracranial atherosclerosis (> or =1 additional lesion outside the symptomatic arterial territory) had lower s-adiponectin levels than those with isolated intracranial atherosclerosis (4.95 +/- 2.63 vs 6.13 +/- 2.84 microg/mL, p = 0.003). In multiple regression analysis, s-adiponectin levels, but not metabolic syndrome, were independently associated with intracranial atherosclerosis. CONCLUSIONS: Symptomatic intracranial atherosclerosis is associated with lower s-adiponectin levels vs other ischemic stroke subtypes.