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.

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.

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.

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.

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis.

BACKGROUND: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. METHODS: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. RESULTS: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. CONCLUSIONS: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

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.

Large cerebral infarction during praziquantel therapy in neurocysticercosis.

BACKGROUND: Large cerebral infarction is a rare complication of neurocysticercosis. Endarteritis by inflammation of the leptomeninges is known to be its cause. CASE DESCRIPTION: A 59-year-old man with known neurocysticercosis developed a large cerebral infarction during praziquantel therapy. A follow-up MRI obtained immediately after his cerebral infarction demonstrated notable decrease in the size of the cysts and more prominent enhancement around the peripheral margins of the cysts and the major vessels in comparison with the initial MRI. Cerebral angiography disclosed occlusions and narrowing of both internal carotid arteries at the supraclinoid portions, where multiple cysts were found on the MRI. CONCLUSIONS: Findings in our patient strongly suggest that a secondary inflammation reaction caused by the destruction of the cysts might have enhanced the process of endarteritis. The possible deleterious effects of praziquantel therapy should be considered in the treatment of patients with subarachnoid cysticerci.