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.

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.

Magnetic resonance spectroscopic determination of a neuronal and axonal marker in white matter predicts reversibility of deficits in secondary normal pressure hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms. However, neuroimaging has failed to predict when shunting will be effective. OBJECTIVE: To investigate whether 1H (proton) magnetic resonance (MR) spectroscopy could predict functional outcome in patients after shunting. METHODS: Neurological state including Hasegawa's dementia scale, gait, continence, and the modified Rankin scale were evaluated in 21 patients with secondary NPH who underwent ventriculo-peritoneal shunting. Outcomes were measured postoperatively at one and 12 months and were classified as excellent, fair, or poor. MR spectra were obtained from left hemispheric white matter. RESULTS: Significant preoperative differences in N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) were noted between patients with excellent and poor outcome at one month (p = 0.0014 and 0.0036, respectively). Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score, and modified Rankin scale to better one month outcome. Predictive value, sensitivity, and specificity for excellent outcome following shunting were 95.2%, 100%, and 87.5%. Multiple regression analysis indicated that NAA/Cho had the best predictive value for one year outcome (p = 0.0032); predictive value, sensitivity, and specificity were 89.5%, 90.0%, and 88.9%. CONCLUSIONS: MR spectroscopy predicted long term post-shunting outcomes in patients with secondary NPH, and it would be a useful assessment tool before lumbar drainage.

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.

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.

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.

[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.

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.

Poor recovery of mitochondrial redox state in CA1 after transient forebrain ischemia in gerbils.

BACKGROUND AND PURPOSE: Several investigations have detected evidence of apoptosis in delayed neuronal death, but controversy prevails regarding this point. Recent studies have implicated mitochondria in apoptotic events. To explore relationships between delayed neuronal death and dysfunction of the respiratory chain, we analyzed mitochondrial redox changes in the gerbil hippocampus. METHODS: We assessed the mitochondrial redox state in gerbil hippocampus before, during, and at various time points after 5 minutes of forebrain ischemia. The redox state was examined with a low-temperature fluorometer. Fluorescence signals of flavoprotein and NADH were measured, and their fluorescence ratio was calculated as a mitochondrial redox ratio (MRR) equal to flavoprotein/(flavoprotein+NADH). RESULTS: Ischemia increased NADH and decreased flavoprotein signals in all hippocampal areas, but reduction in MRR was greater in CA1 than in other areas of the hippocampus. Immediately after recirculation, MRR recovery was delayed in the CA1 and the dentate gyrus, and the reduction in MRR persisted in CA1. CONCLUSIONS: These results suggest that during ischemia CA1 experiences more pronounced hypoxia (state V) than less vulnerable regions. Persistent MRR reduction in CA1 is attributed to dysfunction of the electron transport system, and this phenomenon may be importantly involved in apoptosis.

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.

Metastatic adenocarcinoma presenting as a homogeneously high density mass on CT.

We report a case of metastatic adenocarcinoma to the brain that appeared as a homogeneously hyperdense mass on CT. The lesion was initially diagnosed as an intracerebral hematoma. On serial CT scans, the high density lesion progressively enlarged. Pathology showed coagulation necrosis without hemorrhage or calcification. Analysis of the tumor revealed elevation of the protein content relative to the normal brain. We conclude that the high CT attenuation was due to the elevated protein content.

[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.

[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.

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.

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.

A method to estimate the ratio of absorption coefficients of two wavelengths using phase-modulated near infrared light spectroscopy.

Near infrared spectroscopy is a very useful tool for monitoring the oxygen saturation of living tissue noninvasively. We can calculate the hemoglobin oxygen saturation within tissue, using the ratio of the absorption coefficients (mua) at two different wave lengths of light. Biological tissue has a very high effective scattering factor (mu's), which elongates an optical path length and makes it difficult to compute the mua by the conventional method using continuous light. Phase-modulated spectroscopy (PMS) measures the path length which is a complex function of the mua and mu's. To obtain the ratio for mua, we have to eliminate the effects of the mu's from the obtained value by the PMS method. In this report, we present a theory and an experimental result which show that the inverse of the squared ratio of two phase angle differences at two different separations obtained by two different light wavelengths provides a good estimate of the ratio at these wavelengths.

Nilvadipine, a new calcium channel blocker, reduces ischemic brain injury in rats.

The effects of nilvadipine, a dihydropyridine type calcium channel blocker, on cerebral infarction induced by focal brain ischemia was studied in rats. The area of infarction was measured 24 hr after occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats using triphenyltetrazolium chloride. Nilvadipine, given immediately after MCA occlusion, reduced the area of infarction significantly at doses of 0.32 mg/kg (i.p.) and 3.2, 10 and 32 mg/kg (p.o.). Nicardipine suppressed the area of infarction at a dose of 32 mg/kg (p.o.). The results suggest that nilvadipine is effective against ischemic brain injury.

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.