Visit-to-visit variability in systolic blood pressure is a novel risk factor for the growth of intracranial aneurysms.

BACKGROUND: Although rupture of unruptured intracranial aneurysms (UIAs) is closely associated with UIA growth during follow-up, few studies have investigated how UIAs grow during observation. Hypertension appears to affect the formation of intracranial aneurysms. However, few studies have investigated the association of blood pressure variability with UIA growth. Visit-to-visit variability (VVV) in systolic blood pressure (SBP) is a newly defined concept which appears to be a good predictor of stroke. With this factor in mind, here we conducted a prospective analysis of the results of 2 years of observation of UIAs by magnetic resonance angiography (MRA) and sought to identify risk factors for UIA growth and rupture. METHODS: From December 2006 through June 2010, two hundred patients with 212 UIAs were followed for 2 years. Patient ages ranged from 31 to 91 years. Putative risk factors for the growth of UIAs were evaluated. Subjects were divided into two groups: a UIA growth group consisting of patients whose UIAs increased by 1 mm or more in size or who developed subarachnoid hemorrhage (SAH), and an unchanged group. Brachial blood pressure values were recorded at the time of diagnosis and during follow-up in the outpatient clinic. All blood pressure values were then averaged, and the VVV of SBP was defined as the standard deviation (SD) of a minimum of 5 blood pressure measurements at outpatient visits. RESULTS: UIA growth occurred in 20 patients and SAH occurred in 1 patient. Current smoking tended to be more prevalent in the UIA growth group (p < 0.01). Five of the 12 patients with multiple UIAs showed UIA growth within 2 years and multiplicity was a significant risk factor for UIA growth (p < 0.01). The mean baseline size in the UIA growth group was larger than that in the unchanged group (p = 0.01) and 7 of the 18 patients with large UIAs, categorized as having an initial diameter of 7 mm or more, had an increase in UIA size over the 2 years (p < 0.01). On multivariable logistic regression analysis, current smoking, multiplicity, and UIA size ≥7 mm were significant risk factors for UIA growth. Although no significant difference was seen between the UIA growth and unchanged groups in office SBP during the observation period, VVV in SBP was significantly higher in the UIA growth group than in the unchanged group, and it was significantly and independently associated with UIA growth. CONCLUSIONS: VVV in SBP is a novel risk factor for the growth of UIAs and may be a key factor for the prevention of UIA rupture. Future research is needed to confirm that SBP stability prevents UIA rupture.

Usefulness of intraoperative computed tomography for the evacuation of lobar hemorrhage.

There is a lot of debate on the treatment method for spontaneous intracerebral hemorrhage (ICH). Intraoperative computed tomography (iCT) provides excellent images of cerebrovascular lesions. In this paper, we describe the surgical procedure and the efficacy of iCT during lobar hemorrhage evacuations and subsequent patient outcomes. Fifty-eight patients with lobar hemorrhage were treated using iCT. We performed preoperative cerebral angiography and/or three-dimensional (3D) CT angiography to detect abnormal vessels and identify the spatial relationships between the cerebrovascular structures and the hematoma. After administration of local anesthesia, an enlarged burr-hole was created just above the hematoma. Microsurgical evacuation of the hematoma was performed, and an iCT image was obtained to assess real-time 3D information on residual hematoma or unexpected rebleeding. Mean hematoma volume, evacuation rate, and duration of the surgery were 42 mL, 93 %, and 89 min respectively. Postoperative rebleeding occurred in 1 case. The median Glasgow Coma Scale score upon admission was 12. At discharge, most patients (60 %) had good functional outcomes defined by modified Rankin Scale scores of 0-3. Postoperative neurological findings and consciousness levels showed early improvement. Safe, accurate, and effective evacuation of lobar hemorrhage was possible with iCT as an image-guided intraoperative navigation tool.

Use of preoperative 3D CT/MR fusion images and intraoperative CT to detect lesions that spread onto the brain surface.

OBJECTIVE: Preoperative 3D CT/MR fusion images were prepared for preoperative evaluations and intraoperative assistance for the following lesions: arteriovenous -malformations (AVMs), meningiomas, and metastatic tumors that spread onto the brain surface. METHOD: We prepared 3D CT/MR fusion images for 4 AVMs, 13 meningiomas, and 7 metastatic tumors, and demonstrate representative cases. Data acquired from 16-slice multidetector CT and 1.5-T MRI were used. The volume rendering technique was used. During operations, mobile 16-slice multidetector CT was used to update information. RESULTS: Even after opening the dura mater, the relationship between a brain surface lesion and the surrounding structures on the preoperative 3D fusion images corresponded to the patient's operation field. Updated information via intraoperative CT was useful because operation fields might change owing to the brain shift. These images made extirpations of lesions easier and less invasive. CONCLUSION: Not only the preoperative 3D information, but also intraoperative CT information are beneficial for smooth and safe operations.

Deep cerebral microbleeds are negatively associated with HDL-C in elderly first-time ischemic stroke patients.

BACKGROUND: Cerebral microbleeds (CMBs) detected on T2*-weighted MRI gradient-echo have been associated with increased risk of cerebral infarction. We evaluated risk factors for these lesions in a cohort of first-time ischemic stroke patients. METHODS: Presence of CMBs in consecutive first-time ischemic stroke patients was evaluated. The location of CMBs was classified by cerebral region as strictly lobar (lobar CMBs) and deep or infratentorial (deep CMBs). Logistic regression analysis was performed to determine the contribution of lipid profile to the presence of CMBs. RESULTS: One hundred and sixteen patients with a mean age of 70±10years were recruited. CMBs were present in 74 patients. The deep CMBs group had significantly lower HDL-C levels than those without CMBs. In univariable analysis, advanced periventricular hyperintensity grade (PVH>2) and decreased HDL-C were significantly associated with the deep but not the lobar CMB group. On logistic regression analysis, HDL-C (beta=-0.06, p=0.002) and PVH grade >2 (beta=3.40, p=0.005) were independent determinants of deep CMBs. CONCLUSIONS: Low HDL-C may be a risk factor of deep CMBs, including advanced PVH status, in elderly patients with acute ischemic stroke. Management of HDL-C levels might be a therapeutic target for the prevention of recurrence of stroke.

Predictive value of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio for the prevention of stroke recurrence in Japanese patients treated with rosuvastatin.

BACKGROUND: HMG-CoA-reductase (statin) therapy to reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with coronary heart disease can substantially improve outcomes; however, the benefits of statins in stroke patients, particularly for secondary stroke prevention, remain poorly understood. Moreover, the degree of decrease in LDL-C that is required to prevent the recurrence of stroke is unknown. OBJECTIVE: To determine whether the on-treatment LDL-C/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) is a predictive marker of stroke recurrence in patients with acute ischaemic stroke, and whether medical management of the LDL-C/HDL-C ratio would be of strategic significance for stroke prevention. METHODS: A total of 137 dyslipidaemic patients who had suffered acute ischaemic stroke were enrolled and treated with rosuvastatin 2.5 mg within 24 hours of onset. Blood pressure and serum lipids were assessed at baseline and after 1 month of treatment with rosuvastatin. Fatal and non-fatal stroke events were recorded during a follow-up period of 36 months. We used univariate and multivariate analyses, as well as Kaplan-Meier analysis, to assess the predictive value of various parameters and to identify factors independently associated with stroke recurrence. RESULTS: During a mean follow-up of 34.9 ± 0.8 months, there were ten cases of stroke recurrence. Age, chronic kidney disease (CKD) at baseline, and an on-treatment LDL-C/HDL-C ratio >2 after 1 month of rosuvastatin treatment were predictors of stroke recurrence in univariate analyses. Stepwise regression analysis showed that CKD (standardized adjusted odds ratio [OR] 6.55; 95% confidence interval [CI] 1.12, 36.43; p = 0.030) and on-treatment LDL-C/HDL-C ratio >2 (standardized adjusted OR 9.70; 95% CI 1.70, 55.33; p = 0.011) were independent risk factors for stroke recurrence. Post hoc analysis indicated that more intensive lipid control, to an LDL-C/HDL-C ratio ≤1.5, may reduce the risk of stroke recurrence. CONCLUSION: These results suggest that the use of statin therapy to achieve an on-treatment LDL-C/HDL-C ratio ≤2 is a suitable treatment strategy in patients having suffered acute ischaemic stroke. Further studies are required to confirm the clinical benefits of reducing the on-treatment LDL-C/HDL-C ratio to ≤1.5.

Genetic predisposition to neurological symptoms in lacunar infarction.

OBJECTIVE: Lacunar infarction is a unique stroke entity with characteristic symptoms. However, it is often silent clinically. The possible genetic predisposition to symptoms of lacunar infarction was investigated. METHODS: One-hundred and fifty-one patients with lacunar stroke were consecutively recruited. Lacunar stroke was diagnosed based on both neurological symptoms and lacunar lesion(s), demonstrated by MRI, that were responsible for the symptoms. One-hundred and fifty control subjects with MRI-proven lacunar lesions without neurological symptoms served as controls. There was no significant difference in age, sex and prevalence of known risk factors between cases and controls. Insertion and deletion polymorphisms of the angiotensin-converting enzyme gene (ACE), M235T substitution of the angiotensinogen gene (AGT), and A1133C substitution of type 1 receptor of the angiotensin II gene were determined. RESULTS: The frequency of ACE D allele was significantly higher in symptomatic patients compared with asymptomatic subjects (0.44 vs. 0.36, p < 0.05). The genotype distribution of AGT was significantly different between symptomatic and asymptomatic patients (chi(2) = 6.6, p = 0.037). Multiple logistic regression analysis revealed that ACE gene and AGT genotypes were independently associated with the neurological manifestation of lacunar infarction. In subjects with 1 lacuna, the odds ratio of the ACE DD genotype for symptomatic manifestation was 4.98 (95% CI 1.25-19.9). In subjects with 4 or more lacunae, the odds ratio of the ACE II genotype for symptomatic manifestation was 0.24 (95% CI 0.10-0.56). Furthermore, the ACE gene polymorphism was significantly different between symptomatic patients with a single lacuna and asymptomatic subjects with 4 or more multiple lacunar infarctions (chi(2) = 10.6, p = 0.005). CONCLUSION: These findings suggest that 2 subtypes of lacunar infarction, single symptomatic lacuna and multiple asymptomatic lacunae, may possess different genetic backgrounds. Subjects with the ACE DD genotype could be more predisposed to be symptomatic in first-ever lacunar stroke, while the ACE II genotype may convey resistance to symptoms even after multiple lacunar strokes. Polymorphism of genes of the renin-angiotensin system could be involved in the manifestation of neurological symptoms of lacunar infarction.

Glutamine transport at the blood-brain and blood-cerebrospinal fluid barriers.

Glutamine has multiple physiological and pathophysiological roles in the brain. Because of their position at the interface between blood and brain, the cerebral capillaries and the choroid plexuses that form the blood-brain barriers (BBB) and blood-cerebrospinal fluid (CSF) barriers, have the potential to influence brain glutamine concentrations. Despite this, there has been a paucity of data on the mechanisms and polarity of glutamine transport at these barrier tissues. In situ brain perfusion in the rat, indicates that blood to brain L-[14C]glutamine transport at the blood-brain barrier is primarily mediated by a pH-dependent, Na(+)-dependent, System N transporter, but that blood to choroid plexus transport is primarily via a pH-independent System N transporter and a Na(+)-independent carrier that is not System L. Transport studies in isolated rat choroid plexuses and primary cultures of choroid plexus epithelial cells indicate that epithelial L-[14C]glutamine transport is polarized (apical uptake>basolateral) and that uptake at the apical membrane is mediated by pH dependent System N transporters (identified as SN1 and SN2 by polymerase chain reaction) and the Na(+)-independent System L. Blood-brain barrier System N transport is markedly effected by cerebral ischemia and may be a good marker of endothelial cell dysfunction. The multiple glutamine transporters at the blood-brain and blood-CSF barriers may have role in meeting the metabolic needs of the brain and the barrier tissues themselves. However, it is likely that the main role of these transporters is removing glutamine, and thus nitrogen, from the brain.