Small Cerebral Infarction Research Articles

Ｖａｓｃｕｌａｒ ｄｅｐｒｅｓｓｉｏｎを呈したｒａｄｉａｔｉｏｎ ｉｎｄｕｃｅｄ ａｒｔｅｒｉａｌ ｉｎｊｕｒｙによる総頚動脈閉塞症の１例

A 71-year-old woman was admitted to our hospital with depression that had begun 1 month prior to admisson. Eight years before, she had received radiation therapy (total 60 Gy) for laryngeal cancer. Neurological examination on the admission was normal, but self-rating depression scale (SDS) score showed severe depression. Magnetic resonance imagings demonstrated a small old cerebral infarction in the right cingulate gyrus and multiple lacunar infarctions in subcortical regions. Angiography revealed complete occlusion of the right common carotid artery (CCA) and severe stenotic lesions of the left CCA. Positron emission tomography (PET) showed a decrease of cerebral blood flow (CBF) in the bilateral cerebral hemispheres. The patient underwent a reconstructive surgery for the right CCA. There was no adhesion of skin and subcutaneous tissue, and after arteriotomy the atheromatous plaque was easily removed. After the operation, she was relieved of depression and her SDS score remarkably improved. Postoperative angiography showed the recanalization of the right CCA, and PET revealed an increase of CBF of bilateral cerebral hemispheres. Vascular depression (VD) is a mood disorder caused by cerebrovascular disease, especially cerebral infarctions. In this case, the depression improved remarkably after the carotid endarterectomy, which resulted in an increase of CBF. This case suggests that there may be CBF-dependent and surgically treatable VD in patients with major depressive disorder.

The pathology of ischemic-vascular dementia: An update

In Western memory clinic-based series, ischemic-vascular dementia (IVD) is seen in 8–10% of cognitively impaired elderly subjects. Its prevalence in autopsy series ranges from 0.03% to 58% with reasonable values of 4–10%, while in Japan, IVD is seen in 22–35% and mixed-type dementia (MTD) (Alzheimer disease/AD+IVD) in 6–11%. In a large Viennese autopsy series, “pure” IVD was observed in 9.4% of demented elderly and in 2.9% of those clinically diagnosed as possible/probable AD MTD was observed in 3.1% and 1.3% respectively. The major morphological types of IVD are multi-infarct encephalopathy (MIE), small vessel infarct type-strategic infarct dementia (SID), subcortical arteriosclerotic leukoencephalopathy (Binswanger), multilacunar state, mixed cortico-subcortical type, granular cortical atrophy, and post-ischemic encephalopathy. In contrast to previous suggestions that IVD is mainly the result of large hemispheral infarcts or losses of over 100 ml of brain tissue, recent data indicate that cognitive decline is commonly associated with widespread small ischemic or vascular lesions (microinfarcts, lacunes) throughout the brain with predominant involvement of the basal ganglia, white matter, and hippocampus. The lesion pattern of “pure” IVD, which is related to arteriolosclerosis and hypertensive microangiopathy, differs from that in mixed-type dementia, more often showing large infarcts. Although recent studies suggest that concomitant small cerebral infarcts do not significantly influence the overall rate of cognitive decline in AD patients or may be important for mental decline in early AD, both mild AD pathology and microvascular cerebral lesions appear to be common and may interact in “unmasking” or promoting dementia.

Mechanisms of acute cerebral infarctions in patients with middle cerebral artery stenosis: a diffusion-weighted imaging and microemboli monitoring study.

Although most therapeutic efforts and experimental stroke models focus on the concept of complete occlusion of the middle cerebral artery as a result of embolism from the carotid artery or cardiac chamber, relatively little is known about the stroke mechanism of intrinsic middle cerebral artery stenosis. Differences in stroke pathophysiology may require different strategies for prevention and treatment. We prospectively studied 30 consecutive acute ischemic stroke patients with middle cerebral artery stenosis detected by transcranial Doppler and magnetic resonance angiography. Patients underwent microembolic signal monitoring by transcranial Doppler and diffusion-weighted magnetic resonance imaging. Characteristics of acute infarct on diffusion-weighted magnetic resonance imaging were categorized according to the number (single or multiple infarcts) and the pattern of cerebral infarcts (cortical, border zone, or perforating artery territory infarcts). The data of microembolic signals and diffusion-weighted magnetic resonance imaging were assessed blindly and independently by separate observers. Diffusion-weighted magnetic resonance imaging showed that 15 patients (50%) had single acute cerebral infarcts and 15 patients had multiple acute cerebral infarcts. Among patients with multiple acute infarcts, unilateral, deep, chainlike border zone infarcts were the most common pattern (11 patients, 73%), and for single infarcts, penetrating artery infarcts were the most common (10 patients, 67%). Microembolic signals were detected in 10 patients (33%). The median number of microembolic signals per 30 minutes was 15 (range, 3-102). Microembolic signals were found in 9 patients with multiple infarcts and in 1 patient with a single infarct (p = 0.002, chi(2)). The number of microembolic signals predicted the number of acute infarcts on diffusion-weighted magnetic resonance imaging (linear regression, adjusted R(2) =0.475, p < 0.001). Common stroke mechanisms in patients with middle cerebral artery stenosis are the occlusion of a single penetrating artery to produce a small subcortical lacuna-like infarct and an artery-to-artery embolism with impaired clearance of emboli that produces multiple small cerebral infarcts, especially along the border zone region.

Magnetic resonance imaging findings and postoperative neurologic dysfunction in elderly patients undergoing coronary artery bypass grafting

Background. Small cerebral infarctions are common in elderly patients, but the association between the magnetic resonance imaging finding and neurologic dysfunction after coronary artery bypass grafting has not been evaluated. Methods. We determined, prospectively, whether varying degrees of abnormal findings on magnetic resonance images of the brain increased the incidence of preoperative cognitive decline, postoperative neuropsychological dysfunction, and stroke in 421 elderly patients (≥ 60 years) undergoing coronary artery bypass grafting. Results. Control patients (almost normal or leukoaraiosis, n = 212) had rates of postoperative neuropsychological dysfunction (7%) and stroke (1.4%); the small infarctions group (some small infarctions, n = 126) had rates of 13% and 5.6%, respectively; whereas patients with multiple infarctions (multiple small infarctions or broad infarctions, n = 83) had rates of 20% and 8.4%, respectively ( p = 0.004, p = 0.013). In the group with multiple infarctions, 49 patients (59%) were asymptomatic and 21 patients (25%) had cognitive decline. Stepwise logistic regression analysis demonstrated that the significant predictors of multiple small infarctions or large infarctions were history of cerebrovascular disease, renal insufficiency, cognitive decline, and cerebral arteriosclerosis. Conclusions. Multiple infarctions significantly increase the risk of neurologic dysfunction after coronary artery bypass grafting. Routine screening for preoperative cognitive decline should be performed to detect underlying ischemic cerebral disease in elderly patients.

Age of menarche in contemporary British teenagers: survey of girls born between 1982 and 1986

<h3>Background</h3> ‘Silent’ cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). <h3>Objective</h3> To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact...

The Strategy for Internal Carotid Stenosis with Thrombus

We report 3 cases of internal carotid artery (ICA) stenosis with thrombus. The initial symptom is transient ischemic attack (TIA) in 1 case, and cerebral infarction due to artery-to-artery embolism in 2 cases.We started anticoagulation and antiplatelet therapy after the angiography on admission in all cases. Carotid endarterectomy (CEA) was performed in 1 case after confirming the disappearance of the thrombus 1 month after the initial attack, although small cerebral embolic infarction happened during this period. In the other cases, percutaneous transluminal angioplasty (PTA) and stenting was performed using the protective technique about 2 weeks after the initial attack without embolic complication. Postoperative angiography showed sufficient dilatation. It seemed that PTA/stenting using the protection system was one of the alternatives for ICA stenosis with thrombus.

Small concomitant vascular lesions do not influence rates of cognitive decline in patients with Alzheimer disease.

To determine the relation between concomitant small cerebral infarction and clinical progression of Alzheimer disease (AD). A retrospective clinicopathologic study of patients with AD. We searched the databases of the University of California, San Diego, Alzheimer's Disease Research Center, La Jolla, for patients with an autopsy diagnosis of definite AD with or without a concomitant small cerebral infarction. Clinical and neuropsychologic data obtained during longitudinal follow-up were available for 201 subjects with AD neuropathologic features and 36 with AD and concomitant cerebral infarcts (volume, < 10 cm(3)). The rates of cognitive decline on the Mini-Mental State Examination and the Dementia Rating Scale were each calculated and compared between the 2 groups. The age at death was significantly (P = .05) higher and the Braak stage was lower in patients with mixed AD and infarct pathological features compared with those with AD pathological features only. The rate of cognitive decline over time was not significantly (P > or = .20 for all) different between the 2 groups. There was a trend for the presence of a cerebral infarct to be associated with more severe clinical dementia (P =.08) as measured by the Dementia Rating Scale, but no such trend for the Mini-Mental State Examination. This clinicopathologic correlation study suggests that concomitant small cerebral infarcts with a total volume of less than 10 cm(3) do not significantly influence the overall rate of global cognitive decline in patients with AD. Arch Neurol. 2000;57:1474-1479

A new model of cerebral microthrombosis in rats and the neuroprotective effect of a Rho-kinase inhibitor.

The aim of this study was to develop a new model of stroke based on endothelial damage and thrombotic occlusion in a perforating artery, leading to small cerebral infarcts and neurological deficits in rats. Moreover, the neuroprotective efficacy of fasudil, a rho-kinase inhibitor, was investigated in this model. Fifty-six male Sprague-Dawley rats were used in the present study. Rats were anesthetized with sodium pentobarbital, and 100 microg of sodium laurate was injected into the left internal carotid artery on days 1 and 3. The thrombus induction and consequent of ischemic brain damage were examined by histopathological analyses and neurological deficit scoring in a posture reflex test. To investigate the neuroprotective effects of fasudil, 1 or 10 mg/kg was administered intraperitoneally 5 minutes after the first injection of sodium laurate and once daily thereafter on the following 2 days. One hour after the injection of sodium laurate, microscopic examination of phosphotungstic acid hematoxylin-stained sections (n=5) revealed that microthrombi containing fibrin strands obstructed the perforating arteries in the ipsilateral hemisphere. Under a transmission electron microscope (n=6), endothelial cells appeared exfoliated and the vascular lumen was obstructed by a thrombus composed of degranulated platelets, fibrin, leukocytes, and erythrocytes. No evidence of endothelial cell damage or thrombus could be found in the ipsilateral side of the pial artery (middle cerebral artery). Twenty-four hours after the second injection of sodium laurate (day 4), 13 of 15 rats (86.6%) showed mild to severe neurological deficits. Multiple small cerebral infarcts were observed in the hippocampus, cortex, and thalamus. Treatment with fasudil (1 and 10 mg/kg, n=15 each) resulted in a significant improvement in neurological deficits. Fasudil also significantly reduced the area of cerebral infarction. We present a new model of stroke in rats, in which the perforating arteries are selectively occluded by microthrombi. This model is useful to investigate the pathophysiology and treatment of small cerebral infarction, which is caused by perforating arterial occlusive diseases such as lacunar infarcts. Fasudil may be beneficial in the treatment of acute ischemic stroke.

Cerebral infarctions: evaluation with single-axis versus trace diffusion-weighted MR imaging.

Our purpose was to determine the usefulness of single-axis diffusion-weighted imaging versus trace diffusion-weighted imaging in the evaluation of cerebral infarctions. Twenty-six patients harboring 34 infarctions were examined using single-axis and trace diffusion-weighted imaging within 48 hr of the onset of symptoms. Two neuroradiologists who were not aware of the clinical findings reviewed all images obtained with both techniques and noted the following: type of infarction (small [<15 mm] versus territorial), location of infarction, presence of infarction (seen only on single-axis images, seen only on trace images, seen on both), lesion conspicuity (better on single-axis images, better on trace images, or equal on both), and lesion size (larger on single-axis images, larger on trace images, or equal on both). Differences in opinion were resolved by consensus. Of the 18 small and 16 territorial infarctions, all were identified on both single-axis and trace imaging. Lesion conspicuity was judged to be slightly better on trace images for both types of infarctions. Lesion size was judged to be larger on single-axis images for territorial infarctions. Both single-axis and trace diffusion-weighted imaging showed all small and territorial cerebral infarctions. Both types of infarctions were slightly larger on single-axis images but this did not affect correct interpretation in any case. The single-axis technique provided sufficient information for the diagnosis of cerebral infarction in our clinical settings.

A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion

Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic–ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.

Targeted inhibition of intrinsic coagulation limits cerebral injury in stroke without increasing intracerebral hemorrhage.

Agents that restore vascular patency in stroke also increase the risk of intracerebral hemorrhage (ICH). As Factor IXa is a key intermediary in the intrinsic pathway of coagulation, targeted inhibition of Factor IXa-dependent coagulation might inhibit microvascular thrombosis in stroke without impairing extrinsic hemostatic mechanisms that limit ICH. A competitive inhibitor of native Factor IXa for assembly into the intrinsic Factor X activation complex, Factor IXai, was prepared by covalent modification of the Factor IXa active site. In a modified cephalin clotting time assay, in vivo administration of Factor IXai caused a dose-dependent increase in time to clot formation (3.6-fold increase at the 300 micrograms/kg dose compared with vehicle-treated control animals, P < 0.05). Mice given Factor IXai and subjected to middle cerebral artery occlusion and reperfusion demonstrated reduced microvascular fibrin accumulation by immunoblotting and immunostaining, reduced 111In-labeled platelet deposition (42% decrease, P < 0.05), increased cerebral perfusion (2.6-fold increase in ipsilateral blood flow by laser doppler, P < 0.05), and smaller cerebral infarcts than vehicle-treated controls (70% reduction, P < 0.05) based on triphenyl tetrazolium chloride staining of serial cerebral sections. At therapeutically effective doses, Factor IXai was not associated with increased ICH, as opposed to tissue plasminogen activator (tPA) or heparin, both of which significantly increased ICH. Factor IXai was cerebroprotective even when given after the onset of stroke, indicating that microvascular thrombosis continues to evolve (and may be inhibited) even after primary occlusion of a major cerebrovascular tributary.

Alcohol and Stroke: A Community Case-Control Study in Asturias, Spain

The relationship between alcohol consumption and stroke is uncertain. Heavy alcohol consumption has been associated with an increased risk of stroke, while light drinking appears to be protective. However, the evidence is not uniform. We sought to examine the relationship between alcohol consumption and stroke, according to stroke type. We performed a population-based case-control study from September 1990 to December 1991. The study comprised 467 incident cases of stroke and 477 controls aged between 40 and 85. Case was defined following WHO criteria and control was randomly selected from the study base population. Alcohol exposure was obtained by medical interview. We found that consumption of less than 30 g./day of alcohol was protective against all stroke types combined, the multivariated adjusted odds ratio (OR) was 0.58 (95% confidence interval [CI], 0.41–0.83). Moderate alcohol drinking is also protective against all cerebral infarction combined (OR = 0.53; 95% CI, 0.35–0.80) and cortical infarction (OR = 0.40; 95% CI, 0.18–0.86). Drinking up to 30 g/day of alcohol has a borderline protective effect on deep cerebral infarction (OR = 0.40; 95% CI, 0.16–1.02) and has no effect on intracerebral hemorrhage (OR = 0.88; 95% CI, 0.44–1.74). Heavy alcohol drinking, over 140 g/day, is a risk factor for all stroke types combined (OR = 3.2; 95% CI, 1.1–9.7), all cerebral infarction combined (OR = 5.0; 95% CI, 1.5–16.3), small deep cerebral infarction (OR = 9.7; 95% CI, 2.6–36.7), intracerebral hemorrhage (OR = 6.2; 95% CI, 1.3–24.0), and is marginally associated with superficial cerebral infarction (OR = 4.6; 95% CI, 1.0–20.6). The relationship between alcohol and stroke depends on the alcohol dose and the pathology of the disease. Atherosclerosis of the large and medium cerebral arteries is found mainly in superficial cerebral infarction, and this type of stroke shows a J-shaped relationship with alcohol similar to that found in coronary heart disease, suggesting that they are similar diseases. On the other hand, arteriosclerosis of the penetrating arteries has been found in deep cerebral infarction and intracerebral hemorrhage, while atherosclerosis is not prominent. This may explain why alcohol does not have a protective effect on cerebral hemorrhage whereas heavy drinking is a strong risk factor in these two types of stroke.

Effects of Hyperglycemia on Small Cerebral Infarctions in Awake Rabbits

This study concerns the effects of hyperglycemia on small infarctions in the rabbit brain. Small ischemic foci were produced in both normoglycemic (6 mM) and hyperglycemic (25 mM) rabbits, by injecting small plastic beads into the left heart ventricle under short-acting anaesthesia. 2-deoxy-D-[14C]glucose (2-DG) autoradiography was used to trace ischemic regions in which glucose uptake was increased, either shortly after, or six hours after, the embolization (in awake rabbits). A lesion was characterized by a 2-DG activity > 120%. The obtained freeze-dried sections were inspected for infarcts (with lost tissue structure and increased transparency to light).In the short experiments (< 1 hour), lesions could be detected throughout the brains, indicating hypoxic regions with enhanced glycolysis. In some foci, mostly located in the basal ganglia (the region containing the largest lesions), a central dip could be seen in the 2-DG accumulation, suggesting a poor glucose supply to the ischemic core. The lesions in the basal ganglia of rabbits that were made hyperglycemic were smaller and did not show such dips. No infarcts could be found in the tissue sections.In the long experiments (6 hours), both infarcts and lesions could be found. The impact of hyperglycemia on the infarction process in different brain regions was evaluated by measuring the infarct volumes, and by evaluating the fraction of infarcts - number of infarcts found in freeze-dried sections/number of foci (both lesions and infarcts) found in the 2-DG autoradiograms. Hyperglycemia reduced the fraction of infarcts in the cortex, and reduced the size of infarcted areas in the brain stem. In summary, this study shows that the impact of hyperglycemia on the ischemic outcome depends on where in the brain the ischemic focus is located. This adds interesting information as to what is known about the general effects of glucose on cerebral ischemia.

SEVERITY OF ATHEROSCLEROSIS IN BRAIN, CAROTID ARTERY AND ASCENDING AORTA

Introduction: Coronary heart disease is a known risk factor for systemic atherosclerosis. Cerebral ischemic disorders and carotid stenosis tend to impair the cerebral autoreguration mechanism, which may cause hypoperfusion during cardiopulmonary bypass (CPB) [1]. Advanced atheromatous disease of the ascending aorta is a major risk factor for perioperative stroke [2]. We studied whether varying degrees of the total atherosclerotic score of brain, carotid artey and ascending aorta predicted postoperative neurological dysfunction in patients undergoing coronary artery bypass grafting (CABG). Methods: 138 patients underwent preoperative magnetic imaging and angiography (MRI, MRA) to detect small cerebral infarctions (grade: 0-4) and carotid artery stenosis (grade: 0-3). The degree of atherosclerosis of the ascending aorta (grade: 1-3) was identified by intraoperative epiaortic ultrasonography. Patients underwent the Hasegawa-dementia scale (full score 30) [3] as a neuropsychological (NP) test in the preoperative period (baseline), and on the first and seventh days postoperatively. The presence of stroke was confirmed by a staff neurologist using preoperative MRI and postoperative MRI and CT. Patients were divided into 3 groups according to total atherosclerotic score: GroupL, low score <or=to 4 (n=100); GroupI, intermediate score = 5 (n=25) and GroupH, high score >or=to 6 (n=13). The incidence of NP dysfunction and stroke after CPB were compared among the 3 groups. Data were analyzed by Chi squared test and ANOVA. P<0.05 was required for significance. Results: Multiple small infarctions, carotid stenosis and severe aortic atherosclerosis were found to be predictive risk factors for postoperative NP dysfunction. The incidence of NP dysfunction after CPB was significantly higher in GroupH than in the other two groups in postoperativedays 1 and 7 (p<0.001, P<0.001, Table 1). No stroke occurred in 113 patients with aortic grade 1 or 2, while the intraoperative stroke rate was 8.0% (2/25) for grade 3 (p=0.003).Table 1Conclusions: The incidence of NP dysfunction after CPB was demonstrated to increase in patients who had a higher total atherosclerotic score. Perioperative evaluation of atherosclerotic disease in the brain, carotid artery and aorta is useful for applying preventive measure of postoperative neurological dysfunction after CABG.

Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice.

Intravenous tissue plasminogen activator (tPA) is used to treat acute stroke because of its thrombolytic activity and its ability to restore circulation to the brain. However, this protease also promotes neurodegeneration after intracerebral injection of excitotoxins such as glutamate, and neuronal damage after a cerebral infarct is thought to be mediated by excitotoxins. To investigate the effects of tPA on cerebral viability during ischemia/reperfusion, we occluded the middle cerebral artery in wild-type and tPA-deficient mice with an intravascular filament. This procedure allowed us to examine the role of tPA in ischemia, independent of its effect as a thrombolytic agent. tPA-deficient mice exhibited approximately 50% smaller cerebral infarcts than wild-type mice. Intravenous injection of tPA into tPA-/- or wild-type mice produced larger infarcts, indicating that tPA can increase stroke-induced injury. Since tPA promotes desirable (thrombolytic) as well as undesirable (neurotoxic) outcomes during stroke, future therapies should be aimed at countering the excitotoxic damage of tPA to afford even better neuroprotection after an acute cerebral infarct.

Utility of Diffusion-weighted MR Imaging in Acute Stage of Small Cerebral Infarction

Utility of Diffusion-weighted MR Imaging in Acute Stage of Small Cerebral Infarction

Diffusion-weighted magnetic resonance imaging in the diagnosis of cerebral infarct

Forty-one patients demonstrating clinical symptoms for cerebral infarction were investigated by magnetic resonance imaging with diffusion-weighted echo-planar imaging (DWI) and T2-weighted imaging (T2WI). In 8 patients only DWI showed the cerebral lesions clearly. One patient with positive DWI and T2WI suffered from HSV encephalitis. DWI is superior to T2WI in assessment of small cortical infarcts and cerebral infarction in patients with preexisting vascular lesions. DWI is not specific, so other causes like cerebral hematoma and encephalitis have to be considered.

Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a mendelian condition causing stroke and vascular dementia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited condition whose key features include recurrent subcortical ischemic events, migraine attacks and vascular dementia in association with diffuse white-matter abnormalities seen on neuroimaging. Pathologic examination shows multiple small deep cerebral infarcts, a leukoencephalopathy and a nonatherosclerotic nonamyloid angiopathy involving mainly the media of small cerebral arteries. To progress in understanding the pathophysiological mechanisms of this condition, we undertook the identification of the mutated gene. We mapped the CADASIL gene on chromosome 19p13.1. More than 120 families have been referred to our lab. Genetic linkage analysis of 33 of these families allowed us to reduce the size of the genetic interval to less than 1 cM and to demonstrate the genetic homogeneity of this condition. In the absence of any candidate gene, we undertook positional cloning of this gene. We identified, within the CADASIL critical region, the human Notch3 gene, whose sequence analysis revealed deleterious mutations in CADASIL families co-segregating with the affected phenotype. These data establish that this gene causes CADASIL. Identification of the CADASIL gene will provide a valuable diagnostic tool for clinicians and could be used to estimate the prevalence of this underdiagnosed condition. It should help in the understanding of pathophysiological mechanisms of CADASIL and vascular dementia.

A randomised controlled trial of feedback to general practitioners of their prophylactic aspirin prescribing

<h3>Background</h3> ‘Silent’ cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). <h3>Objective</h3> To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact...

Dietary sodium chloride and potassium have effects on the pathophysiology of hypertension in humans and animals

A diet high in NaCl can raise blood pressure in susceptible people and animals, probably by similar mechanisms. The possibly harmful effects of a high-NaCl diet are not unexpected because both prehistoric humans and mammals evolved in a low-NaCl environment. Evolutionary forces molded mammals to adapt well to a low sodium intake; modern high NaCl intakes go against this adaptation. A high-NaCl diet can cause premature mortality by raising blood pressure in susceptible people. We have new evidence that in hypertension, a high-NaCl diet can cause a great increase in mortality even though it does not cause a further blood pressure rise, partially because of multiple small cerebral infarcts. Recent evidence also indicates that a high-potassium diet reduces the rise of blood pressure caused by a high-NaCl diet, whereas a low-normal potassium intake encourages an NaCl-induced blood pressure rise. The combination of a tendency by the kidneys to retain NaCl together with a high NaCl intake can produce a blood pressure rise. This combination tends to cause NaCl retention, which can trigger blood pressure rises in susceptible humans and animals. Such blood pressure rises can augment renal NaCl excretion and regain the previous NaCl balance. In Dahl salt-sensitive rats several renal abnormalities encourage sodium retention. By analogy, renal "abnormalities" are probably present in people susceptible to hypertension.