Association between excessive supraventricular ectopy and subclinical cerebrovascular disease: a population-based study.

BACKGROUND AND PURPOSE: The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle-aged to older cohort with neither apparent stroke nor atrial fibrillation. METHODS: We conducted a cross-sectional population-based study of 462 men (mean age, 68.1 years) who underwent 24-h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. RESULTS: A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable-adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06-2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02-2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86-2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. CONCLUSIONS: The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke.

Brain proton magnetic resonance spectroscopy and brain atrophy in myotonic dystrophy.

OBJECTIVES: To evaluate by magnetic resonance spectroscopy the age-related cerebral alterations present in myotonic dystrophy (MD) and to compare these results with those obtained by magnetic resonance imaging. DESIGN: Twenty-one patients (aged 16-63 years) with MD were compared with 16 age-matched healthy control subjects. RESULTS: In magnetic resonance spectroscopy, the mean (+/- SD) ratio of N-acetylaspartate to creatine and phosphocreatine in the patients with MD (1.09 +/- 0.32) was significantly lower than that in the control subjects (1.93 +/- 0.43) (P<.001). The mean ratio of N-acetylaspartate to choline-containing compounds in the patients with MD (1.70 +/- 0.44) was also significantly lower than that in the control subjects (2.75 +/- 0.53) (P<.001). These changes could be observed already in the younger patients. In magnetic resonance imaging, the mean brain area was significantly decreased and the mean ventricular space was significantly increased in patients with MD compared with the control subjects. Although we have confirmed brain atrophy in patients with MD in previous reports, a regression analysis indicated that the brain shrinks progressively with age in patients with this disorder and in control subjects, resulting in overlapping values for younger subjects. CONCLUSION: Magnetic resonance spectroscopy indicates that the cerebral abnormalities in patients with MD may be present at an early stage, when the results of magnetic resonance imaging studies are still equivocal.

Three-dimensional redox image of the normal gerbil brain.

Regional differences in the redox ratio were studied in the gerbil brain. Brains were frozen using an in situ funnel-freezing method, and sliced coronally for scanning of mitochondrial redox imaging. The relative local redox ratio of nicotinamide-adenosine dinucleotide to its reduced form was calculated from fluorescence signals of intrinsic fluorochromes, i.e. reduced nicotinamide-adenosine dinucleotide and flavoproteins, using a high resolution fluorometer developed in our laboratory. Twelve consecutive coronal images were obtained from each of 10 gerbils. The mean value of the regional redox ratio in both the cerebral and cerebellar gray matter were found to be significantly lower than that in the cerebral and cerebellar white matter (P < 0.01, Mann-Whitney test). Local differences in the redox ratio were also found among subregions of gray matter. The redox ratio in the globus pallidus was significantly higher than values in other subregions of gray matter (P < 0.01, Mann-Whitney test) We postulate that a high concentration of the reduced form of pyridine nucleotide is maintained to provide redox energy for rapid turnover of ATP in the areas of high energy consumption.

Cortical and subcortical vestibular response to caloric stimulation detected by functional magnetic resonance imaging.

The posterior insula, central sulcus, and inferior parietal lobule including the intraparietal sulcus have been considered the vestibular cortex based on functional brain mapping in humans as well as experiments in lower primates. The same regions receive optokinetic, visual, and proprioceptive projections. We examined the cortical and subcortical projection of vestibular activity with visual and proprioceptive input eliminated during caloric stimulation (CS), using functional magnetic resonance imaging (fMRI). Single-shot gradient-echo echoplanar image (EPI) volumes were sensitive to BOLD contrast in oblique orientation. We adopted a pharmacokinetic model for analysis of imaging data from 10 subjects as a group. The insular gyrus, intraparietal sulcus, superior temporal gyrus, hippocampus, cingulate gyrus, and thalamus showed activation by CS. Cortical and subcortical activation during CS in the present study was observed within regions less precisely delineated by other methods. As intraparietal sulcus activation showed right hemispheric dominance, this region may have an oculomotor projection as well as the vestibular input.

Stereopsis-processing regions in the human parieto-occipital cortex.

We performed fMRI on the human parieto-occipital cortex in order to identify the neural processing regions of stereopsis. Visual stimulation for stereopsis was performed with a random-dot stereogram displayed in the image guides of a new binocular visual stimulation device that we developed. Interestingly, regions from the dorsal portion of the occipital lobe to the superior parietal lobule were activated by binocular disparity, while the inferior parietal lobule was not activated. Moreover, these regions were shown as dominant in the right hemisphere. Functional brain mapping revealed that the processing regions of stereopsis were dorsally located in parieto-occipital cortex, and that the superior parietal lobule is an important region for neural processing of human stereopsis.

Rupture of previously unruptured giant carotid aneurysm after superficial temporal-middle cerebral artery bypass and internal carotid occlusion.

A 51-year-old woman with an unruptured giant aneurysm of the internal carotid artery was treated by gradual occlusion of the internal carotid artery in the neck combined with a superficial temporal artery to middle cerebral artery bypass graft. Visual field defects improved after the operation, and thrombosis of the aneurysm was confirmed by angiography and computed tomography. Nevertheless, a fatal hemorrhage occurred 34 days after the final turn of the Selverstone clamp. The possible mechanism of rupture of the apparently thrombosed aneurysm is discussed. There is a risk of rupture of the aneurysm as long as the aneurysmal lumen remains after proximal ligation, no matter how small it may be.

Focal brain ischemia model in rats. An experimental study.

Using 74 male rats, anatomical variations of branching of the proximal segment of the middle cerebral artery were studied. In 36 rats (28 Sprague-Dawley rats and eight spontaneously hypertensive rats), the middle cerebral artery and/or its branches were occluded at various sites. Occlusion of the middle cerebral artery at the lateral border of the olfactory tract with or without simultaneous ligation of the ipsilateral common carotid artery rarely caused cerebral infarction in Sprague-Dawley rats. Occlusion of the olfactory branch in addition to the trunk of the middle cerebral artery caused large infarction of the pallium in five of eight Sprague-Dawley rats. Occlusion of the middle cerebral artery at the medial border of the olfactory tract caused infarction in the pallium and/or basal ganglia in five of six rats, and neurologic deficits were severe and persistent. Occlusion of the middle cerebral artery at the lateral border of the olfactory tract in spontaneously hypertensive rats caused large infarction with severe neurologic deficits in all eight animals. Possible factors responsible for such diverse differences and the relative value of each group as an experimental model of focal cerebral ischemia in rats were discussed.

Effects of the calcium antagonist nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats.

We studied the efficacy of preischemic and postischemic systemic treatment with a new calcium antagonist nilvadipine in a permanent focal cerebral ischemia model of spontaneously hypertensive rats. Rats that underwent microsurgical middle cerebral artery occlusion were blindly assigned to a single intraperitoneal injection of nilvadipine (0.32 mg/kg) or the same amount of polyethylene glycol either 15 minutes before, immediately after, 1 hour after, or 3 hours after occlusion of the left middle cerebral artery. Neurologic conditions of rats were closely examined, and rats were killed 24 hours later. Removed brains were sliced coronally, stained with triphenyltetrazolium chloride, and the size of infarct was determined. Although no neurologic improvements were observed in the treated rats, the area of infarcts was significantly reduced in the groups treated before, immediately after, and 1 hour after occlusion of the middle cerebral artery. Treatment started 3 hours after occlusion was ineffective.

Effects of a novel calcium antagonist, KB-2796, on neurologic outcome and size of experimental cerebral infarction in rats.

Effects of a novel calcium 2+ antagonist, KB-2796, on neurologic outcome and size of infarction were studied in the rat model of focal cerebral ischemia. Neurologic deficits were examined from 1 to 24 hours after occlusion of the middle cerebral artery and size of infarction was measured at 24 hours postocclusion. When KB-2796 (10 mg/kg, IP) was given immediately after, or 1 hour after, middle cerebral artery occlusion, marked improvement in neurologic score was seen 1 to 3 hours postocclusion. When given immediately after middle cerebral artery occlusion, size of infarction was also markedly smaller when compared with the control rat. The present study suggests that the calcium 2+ antagonist KB-2796 has brain-protective effects against ischemia even with its administration after induction of ischemia.

Proton magnetic resonance spectroscopy with dementia.

To provide new insights into metabolic changes in the brain of patients with dementia, we performed in vivo localized proton magnetic resonance spectroscopy in nine patients with primary degenerative dementia and in three patients with normal-pressure hydrocephalus. We compared the results with those in 26 healthy volunteers. Measurements of regional cerebral blood flow were performed in seven patients by means of single photon emission computed tomography with amphetamine I 123 as a tracer. The magnetic resonance spectra constantly showed three major peaks corresponding to N-acetylaspartate (NAA), creatine and phosphocreatine (Cr), and choline-containing compounds. There were no age-related changes in the mean area ratio of NAA to Cr in neurologically normal volunteers. The NAA/Cr ratio was significantly reduced in patients with primary degenerative dementia. The reduction of the NAA/Cr ratio was observed even in dementia patients with no significant brain atrophy or reduction in regional cerebral blood flow. No significant reduction of the NAA/Cr ratio was seen in patients with normal-pressure hydrocephalus. The NAA/Cr ratio might reflect the number and/or activity of neuronal cells in the brain. Proton magnetic resonance spectroscopy may well provide a useful tool for early detection of, and further pathophysiological study of, primary degenerative dementia.

Acute focal cerebral ischemia in rats studied by diffusion-weighted magnetic resonance imaging--an experimental study.

BACKGROUND: Temporary occlusion of the cerebral artery is occasionally repeated during neurosurgical operations, but the safety of such a procedure remains to be studied further. METHOD: We studied early changes and reversibility of focal cerebral ischemia and the cumulative effects of repeated ischemic insults in rats using magnetic resonance imaging (MRI). RESULTS: Diffusion-weighted magnetic resonance images (DWI) and determination of signal intensity ratio (SIR) proved to be a valuable measure of studying early changes and reversibility of transient focal cerebral ischemia and cumulative adverse effects of repeated ischemic insults. DWIs showed marked intensity changes shortly after focal cerebral ischemia, while T2-weighted images failed to show hyperintensities until 2.5 hours after the onset of permanent ischemia. The critical period of ischemia in this model was 60 minutes. However, 20 minutes ischemia, when repeated twice with 60 minutes reperfusion in between, showed irreversible damage. CONCLUSION: Repeated insults of focal regional cerebral ischemia may cause irreversible tissue damage even if each ischemic period is less than the critical one.

Speech arrest caused by meningioma--two case reports.

Parasagittal or falx meningioma occasionally causes paroxysmal speech disturbance. A 22-year-old and a 46-year-old female harboring meningiomas suffered recurrent episodes of supplementary motor seizures. Magnetic resonance imaging showed the meningioma compressing the left supplementary motor area. Seizures did not recur after total removal of the tumors.

Shock syndrome induced by bromocriptine test in a patient with prolactinoma--case report.

A 72-year-old male developed shock syndrome after a single dose of bromocriptine. He had undergone uncomplicated subtotal removal of an invasive prolactinoma in our department. The patient had normal ranges of pituitary hormones apart from hyperprolactinemia (167.7 ng/ml) after surgery. An acute suppression test with bromocriptine (2.5 mg per os) was done in the supine position 6 days following surgery. Three and a half hours after bromocriptine administration, he suddenly complained of anterior chest discomfort in bed. Cyanosis and profuse diaphoresis were noted. His blood pressure was 80/60 mmHg. Electrocardiography revealed sporadic premature contractions and slight depression in the ST segments. He recovered in about 10 hours after a rapid infusion of corticosteroid and lactic Ringer solution, and was discharged without sequelae. This is a very rare complication of bromocriptine, but the cardiovascular function of patients taking bromocriptine for therapeutic and diagnostic purpose should be monitored carefully.

[Hydrocephalus after aneurysmal subarachnoid hemorrhage].

Diagnosis of hydrocephalus after aneurysmal subarachnoid hemorrhage has been facilitated by CT, but the true incidence and pathogenesis of the condition remain to be clarified. Extent of ventricular dilatation does not necessarily correlate with clinical symptoms and the indication of shunting operation is by no means definite. Consecutive 117 patients with ruptured aneurysm were retrospectively studied for possible factor(s) for development of hydrocephalus in the chronic stage. The incidence of chronic hydrocephalus was found to be high in those patients with aneurysm of the anterior communicating artery, those harboring acute hydrocephalus, those admitted with higher clinical grades, those showing thick clots and gyral enhancement on initial CT, and those who received tranexamic acid in excess of 30 g.

[Central retinal vein occlusion after embolization for spontaneous carotid cavernous sinus fistula].

A patient with spontaneous carotid-cavernous sinus fistula, who developed central retinal vein occlusion (CRVO) after interventional surgery, was reported. A 78-year-old woman was admitted with symptoms of right abducens palsy and conjunctival injection. Digital subtraction angiography (DSA) revealed bilateral carotid cavernous sinus fistulas supplied by dural branches of the carotid arteries. After embolization of the feeding arteries and the right cavernous sinus using PVA and platinum coils respectively, her symptom improved gradually. Six months after the embolization, she was readmitted because of blurred vision and abducens palsy on the left side. Engorgements of the cavernous sinuses and draining veins, and the shunt flow of the fistula were much less on DSA than those seen previously, but ophthalmologic studies showed an impending central retinal vein occlusion (CRVO) in her left eye. Prognosis of CRVO is generally poor. We discussed the mechanism of CRVO occurring after interventional surgery for CCF and the tactics for preventing it, and early detection of its development.

[Functional MRI of the human brain responses to olfactory stimulation].

Image artifacts such as signal loss or distortion due to intravoxel phase dispersion at the skull base are problematic in analysis by functional MRI (fMRI). Since the olfactory center of the brain is located in the medial temporal and basal frontal areas, it is a challenge to try to detect the Blood Oxygenation Level Dependent (BOLD) effect during fMRI at olfactory stimulation. We examined 20 normal volunteers with a 1.5-T MR system, employing multishot, interleaved echo-planar imaging (EPI). Olfactory stimulation was performed with 2-methyl-1, 3-cyclo-pentanedione, a caramel-like fragrance, by presenting it for 20 seconds with two cycles of rest-stimulus paradigm. Sites of functional activation were identified by correlation analysis with a threshold of p < 0.01. Most commonly activated areas were the orbitofrontal and primary olfactory cortices. Mild activation was also observed in the cingulate gyrus, lateral temporal cortex, cerebellum, parietal and occipital lobes. These results indicate that olfactory stimulation participates in the emotion and behavior processes. Interestingly, broad activation in the "silent" area of the frontal and temporal lobe was also observed in some cases. Multishot EPI was a useful method to evaluate brain activation at the basal level on fMRI.

[Mitochondrial redox change in gerbil hippocampus before and after transient ischemia].

To investigate the basis of neuronal vulnerability we studied mitochondrial redox changes in gerbil hippocampus before and after 5 minutes forebrain ischemia. The brain was frozen by in situ funnel freezing method, and grinned off coronally until exposure of hippocampus. Relative value of regional redox ratio (NAD+/NADH) was obtained from fluorescence signals of intrinsic fluorochromes, i.e., NADH (PN) and flavoproteins (Fp), using a high resolution fluorometer. We calculated a modified redox ratio MRR = FP/(Fp + PN). Each point is displayed in gray scales ranged 16 degrees corresponding to the MRR value of the point; black represents a low MRR value (reduced) and white represents a high value (oxidized). Pyramidal cell layers and the granule cell layers were seen as linear areas of high MRR. The stratum radiatum and stratum orience of the CA 1 subfield showed low MRR compared with other hippocampal regions. During ischemic period, MRR in all subfield of hippocampus had decreased but the decrease was more severe in CA 1 region than in another. Just after recirculation, MRR decreased transiently in dentate and CA 3 areas but was fully recovered in all hippocampal areas with the exception of CA 1 region, where the MRR decreased again 12 hours after recirculation. These results suggest that CA 1 area suffers more pronounced hyoxic condition (state V) than other less vulnerable regions during 5 minutes ischemia. The irreversible reduction of MRR in CA 1 area may result from continuing mitochondrial dysfunction, and this may cause lasting energy shortage in CA 1 neurons that eventually results in slowly progressive cell death.

In vivo detection of amyloid ß deposition using ¹9F magnetic resonance imaging with a ¹9F-containing curcumin derivative in a mouse model of Alzheimer's disease.

Amyloid ß (Aß) deposition in the brain is considered the initiating event in the progression of Alzheimer's disease (AD). Amyloid imaging is widely studied in diagnosing AD and evaluating the disease stage, with considerable advances achieved in recent years. We have developed a novel ¹9F-containing curcumin derivative (named FMeC1) as a potential imaging agent. This compound can exist in equilibrium between keto and enol tautomers, with the enol form able to bind Aß aggregates while the keto form cannot. This study investigated whether FMeC1 is suitable as a ¹9F magnetic resonance imaging (MRI) probe to detect Aß deposition in the Tg2576 mouse, a model of AD. In ¹9F nuclear magnetic resonance (NMR) spectra obtained from the whole head, a delayed decreased rate of F ¹9F signal was observed in Tg2576 mice that were peripherally injected with FMeC1 in comparison to wild-type mice. Furthermore, ¹9F MRI displayed remarkable levels of ¹9F signal in the brain of Tg2576 mice after the injection of FMeC1. Histological analysis of FMeC1-injected mouse brain showed penetration of the compound across the blood-brain barrier and binding to Aß plaques in peripherally injected Tg2576 mice. Moreover, the distribution of Aß deposits in Tg2576 mice was in accordance with the region of the brain in which the ¹9F signal was imaged. FMeC1 also exhibited an affinity for senile plaques in human brain sections. These findings suggest the usefulness of FMeC1 as a ¹9F MRI probe for the detection of amyloid deposition in the brain. Furthermore, the properties of FMeC1 could form the basis for further novel amyloid imaging probes.