Positional relationship between recurrent intracerebral hemorrhage/lacunar infarction and previously detected microbleeds.

BACKGROUND AND PURPOSE: Although MBs, ICH, and LI are secondary to cerebral microangiopathy, it remains unclear whether the location of subsequent ICH/LI corresponds to the previous location of MBs. We performed this study to clarify the positional relationship between recurrent ICH/LI and previously detected MBs. MATERIALS AND METHODS: We evaluated patients with recurrent ICH/LI who had MBs, as shown on prior T2*-weighted MR imaging. We assessed retrospectively whether the location of recurrent ICH/LI corresponded to that of the prior MB. Patients with ICH were divided into the deep ICH group and the lobar ICH group, and the positional relationship between hematoma and previously detected MBs was evaluated. RESULTS: A total of 55 patients, including 34 with recurrent ICH and 21 with recurrent LI were evaluated. Although the location of the LI corresponded to prior MBs in only 1 patient (4.8%), the location of ICH corresponded to prior locations of MBs in 21 patients (61.8%) (OR, 32.3; 95% CI, 3.86-270.3; P < .001). Among the patients with ICH, the correspondence ratio was higher in the deep ICH group (19 of 24 patients, 79.2%) than in the lobar ICH group (2 of 10 patients, 20%) (OR, 15.2; 95% CI, 2.42-95.3; P < .002). CONCLUSIONS: The close positional association between recurrent ICH and prior MBs suggests that MBs represent hemorrhage-prone microangiopathy. In addition, different correspondence ratios between the deep ICH group and the lobar ICH group may be attributable to their different pathogenesis.

Association between cerebral microbleeds on T2*-weighted MR images and recurrent hemorrhagic stroke in patients treated with warfarin following ischemic stroke.

BACKGROUND AND PURPOSE: Although accumulating evidence suggests the presence of microbleeds as a risk factor for intracerebral hemorrhage (ICH), little is known about its significance in anticoagulated patients. The aim of this study was to determine whether the presence of microbleeds is associated with recurrent hemorrhagic stroke in patients who had received warfarin following atrial fibrillation-associated cardioembolic infarction. MATERIALS AND METHODS: A total of 87 consecutive patients with acute recurrent stroke, including 15 patients with ICH and 72 patients with cerebral infarction, were enrolled in this study. International normalized ratios (INRs), vascular risk factors, and imaging characteristics, including microbleeds on T2*-weighted MR images and white matter hyperintensity (WMH) on T2-weighted MR images, were compared in the 2 groups. RESULTS: Microbleeds were noted more frequently in patients with ICH than in patients with cerebral infarction (86.7% versus 38.9%, P = .0007). The number of microbleeds was larger in patients with ICH than in patients with cerebral infarction (mean, 8.4 versus 2.1; P = .0001). INR was higher in patients with ICH than in patients with cerebral infarction (mean, 2.2 versus 1.4; P < .0001). The frequency of hypertension was higher in patients with ICH than in patients with cerebral infarction (86.7% versus 45.8%, P = .0039). Multivariate analysis revealed that the presence of cerebral microbleeds (odds ratio, 7.383; 95% confidence interval, 1.052-51.830) was associated with ICH independent of increased INR and hypertension. CONCLUSION: The presence of cerebral microbleeds may be an independent risk factor for warfarin-related ICH, but more study is needed because of strong confounding associations with elevated INR and hypertension.

Diffuse cerebral white matter T2-weighted hyperintensity: a new finding of general paresis.

General paresis (parenchymatous neurosyphilis) is a rare disease, and in recent years the number of papers published on the magnetic resonance imaging findings has been limited. The findings are as follows: cerebral atrophy; mesiotemporal T2 hyperintensity; ventriculomegaly; pathological T2 hypointensity of the globus pallidus, putamen, the head of the caudate nucleus and thalamus. We present a new finding, diffuse cerebral white matter T2 hyperintensity, observed in a patient with general paresis with a 5-year history of progressive dementia.

Diffusion tensor imaging of cerebral white matter in patients with myotonic dystrophy.

PURPOSE: To determine whether myotonic dystrophy (MyD) patients have diffusion tensor abnormalities suggestive of microstructural changes in normal-appearing white matter (NAWM). MATERIAL AND METHODS: Conventional and diffusion tensor magnetic resonance images of the brain were obtained in 19 MyD patients and 19 age-matched normal control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in white matter lesions (WMLs) and NAWM in MyD patients and in the white matter of normal control subjects. Differences between WML and NAWM values and between MyD patient and control subject values were analyzed statistically. RESULTS: Significantly lower FA and higher MD values were found in all regions of interest in the NAWM of MyD patients than in the white matter of control subjects (P<0.01), as well as significantly lower FA and higher MD values in WMLs than in NAWM of MyD patients (P < 0.05). There was no significant correlation of mean FA or MD values in NAWM with patient age, age at onset, or duration of illness (P>0.1). CONCLUSION: Diffusion tensor imaging analysis suggests the presence of diffuse microstructural changes in NAWM of MyD patients that may play an important role in the development of disability.

Characteristic MRI findings in multiple system atrophy: comparison of the three subtypes.

We reviewed MRI findings in 29 patients with probable multiple system atrophy (MSA) to see whether there were common and or less common neuroradiological findings in the various clinical subtypes. We divided the patients into three clinical subtypes according to initial and predominant symptoms: 14 with olivopontocerebellar atrophy (OPCA), eight with the Shy-Drager syndrome (SDS) and seven with striatonigral degeneration (SND). The patients showed atrophy of the brain stem and cerebellum, high signal on T2-weighted images of the base of the pons and middle cerebellar peduncles, high and low signal on T2-weighted images of the putamen and atrophy of frontal and parietal lobes. The degree of atrophy of the middle cerebellar peduncle and cerebellum was greater in OPCA patients and a high-signal lateral rim to the putamen more frequent in SND. However, all findings were observed in all subtypes, and the degrees of atrophy of the putamen and pons and the frequency of high signal in the base of the pons were similar in the subtypes. We also found atrophy of the cerebral hemispheres, especially the frontal and parietal lobes, but its degree was not significantly different in the various subtypes. Our findings suggest that, although MSA can be divided clinically into three subtypes, most of the features on MRI are common and overlap in the subtypes, independently of the clinical presentation.

Correlation between grade III placenta and plasma antithrombin III activity in full term pregnancy.

We evaluated whether the presence of a grade III placenta correlates with blood hypercoagulability in pregnancy between 37 and 39 weeks of gestation. The placenta was graded by ultrasound in 155 healthy full-term women and the plasma levels of antithrombin III (AT III) activity, thrombin-antithrombin complex (TAT) and D-dimer were correlated with each placental grade. AT III activity levels tended to decrease with advancing placental grade from I to III (p < 0.05). D-dimer showed the same tendency while TAT did not. The incidence of reduced AT III activity levels (<70%) in women with a grade III placenta was about twice those in women with a grade II or I placenta, and that of AT III <80% was 3-fold greater. We concluded that the presence of a grade III placenta in full-term pregnancies correlates with blood hypercoagulability.

Abnormal signals on proton density-weighted MRI of the superior cerebellar peduncle in progressive supranuclear palsy.

OBJECTIVE: To assess MRI signal abnormalities of the superior cerebellar peduncle (SCP) in progressive supranuclear palsy (PSP) patients. MATERIAL AND METHODS: Signal changes were examined on proton density-weighted images (PDWI) and on T2-weighted images (T2WI) of SCP in 9 PSP patients, and findings were compared to those in 20 Parkinson's disease patients and 20 age-matched control subjects. RESULTS: We observed effacement or lack of clarity of the low signal on PDWI in SCP in 4 of 9 PSP patients, but not in any of the Parkinson's disease patients or control subjects. These signal changes were not observed on T2WI. CONCLUSIONS: The signal changes on PDWI may be a specific finding reflecting demyelination and gliosis of SCP in PSP. Our findings suggest that evaluation of SCP on PDWI may be helpful in the diagnosis of PSP patients.

Fetal circulatory responses to maternal blood loss.

We examined the fetal circulatory responses to maternal blood loss in pregnant women during the third trimester. Seven healthy women with placenta previa and singleton pregnancies underwent phlebotomies in an autologous donation program. Four hundred milliliters of blood was collected within 15 min at 34 and 35 weeks of gestation. Continuous electric recordings of fetal heart rate were performed during the first blood collection, and the maternal uterine artery (UtA), umbilical artery (UmA) and fetal middle cerebral artery (MCA) Doppler velocity waveforms were recorded before, immediately after and 24 h after the second collection in each patient. The average fetal heart rate, maternal UtA and UmA pulsatility indices did not change measurably during or after maternal blood collections. However, the average fetal MCA pulsatility index decreased significantly 24 h after maternal blood loss. The observation of a decrease in fetal MCA pulsatility index may indicate delayed fetal asphyxia following mild maternal hemorrhage.

Apparent diffusion coefficient measurements in progressive supranuclear palsy.

We measured the apparent diffusion coefficient (ADC), using diffusion-weighted imaging (DWI) and signal intensity on T2-weighted MRI in the cerebral white matter of patients with progressive supranuclear palsy (PSP) and age-matched normal subjects. In PSP, ADC in the prefrontal and precentral white matter was significantly higher than in controls. There was no significant difference in signal intensity on T2-weighted images. The ADC did correlate with signal intensity. The distribution of the elevation of ADC may be the consequence of underlying pathological changes, such as neurofibrillary tangles or glial fibrillary tangles in the cortex. Our findings suggest that ADC measurement might be useful for demonstrating subtle neuropathological changes.

Serial diffusion-weighted imaging in MELAS.

Clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) resemble those of cerebral infarcts, but the pathogenesis of infarct-like lesions is not fully understood. To characterise these infarct-like lesions, we studied two patients with MELAS using diffusion-weighted (DWI) MRI before and after stroke-like episodes and measured the apparent diffusion coefficient (ADC) in the new infarct-like lesions. These gave high signal on DWI and had much higher ADC than normal-appearing regions. The ADC remained high even 30 days after a stroke-like episode then decreased in lesions, with or without abnormality as shown by conventional MRI. We speculate that early elevation of ADC in the acute or subacute phase reflects vasogenic rather than cytotoxic edema. The ADC of the lesions, which disappeared almost completely with clinical improvement, returned to normal levels, which may reflect tissue recovery without severe damage. To our knowledge, this is the first study of DWI in MELAS.

Native and acid-denatured L-lactate dehydrogenase are different in the lysosomal proteinases involving in their overall degradation.

When native and (LDH) acid-denatured lactate dehydrogenase were incubated with total lysosomal enzymes in vitro, amino acids from their degradation were produced at various acidic pH. The pH profile in the overall degradation of native LDH was markedly different from that of acid-denatured LDH. Disappearance of the 35-kDa subunit of native LDH was markedly suppressed by a low level of cystatin alpha as well as by a general cysteine proteinase inhibitor, N-(L3-trans-carboxyoxirane-2-carbonyl)-L-leucine-3-methylbutylamid e (E-64-c). On the other hand, the degradation of acid-denatured LDH was only slightly suppressed by these inhibitors. It was concluded that at least a part of the proteinases involved in the overall degradation of native LDH is different from the proteinases involved in the degradation of acid-denatured form and a role of a cystatin alpha-sensitive cysteine proteinase is critical in the lysosomal degradation of native LDH, but not in that of acid-denatured form.

Suppression of autophagy by ethionine administration in male rat liver in vivo.

The administration of ethionine to male rats decreased the liver adenosine triphosphate (ATP) levels to about 20% of that in control rats and prevented leupeptin-induced intralysosomal accumulation of cytosolic proteins, including lactate dehydrogenase sequestered into lysosomes by autophagy, and leupeptin-induced increase of lysosomal density. These actions of ethionine were reversed by the subsequent administration of adenine plus methionine. All these findings show that the administration of ethionine to male rats suppresses the autophagic sequestration of intracellular proteins into lysosomes, probably due to ethionine-induced ATP depletion.

[Orthostatic transient unresponsiveness in an elderly patient with severe cerebral arteriosclerosis under antihypertensive medication].

An 80-year-old man who had was administered antihypertensive medication showed repeated transient unresponsiveness during standing and/or walking. Neurological examination showed no focal neurological signs except mild dementia. Head-up tilting examination induced unresponsiveness and a decrease of systolic blood pressure from 111 mmHg to 86 mmHg. This unresponsiveness disappeared 3 minutes later when the blood pressure recovered to 102/64 mmHg. Cerebral angiography demonstrated occlusion in the right internal carotid artery and the right vertebral artery. Severe stenosis was observed at the left internal carotid artery and the left vertebral artery. Discontinuance of the antihypertensive medication reduced the frequency of orthostatic transient unresponsiveness. Elastic stockings in the lower extremities completely prevented the attack; head-up tilting did not induce hypotension with elastic stockings. The transient unresponsiveness in the present case was probably correlated to hemodynamic failure under the condition of severe cerebral arteriosclerosis.

Prenatal diagnosis of acute massive fetomaternal hemorrhage.

We present here 2 cases of acute and 2 cases of chronic massive fetomaternal hemorrhage. A sinusoidal fetal heart rate pattern may indicate chronic fetomaternal hemorrhage, but, when increased variability is observed in fetal monitoring, maternal hemoglobin F should be measured to exclude acute fetomaternal hemorrhage.

[An autopsy case of elderly idiopathic enlargement of the right atrium].

We report an autopsy case of an 88-year-old man with idiopathic enlargement of the right atrium which is considered to be the oldest case reported. The patient was given a diagnosis of atrial fibrillation at the age of 75 years, when he developed congestive heart failure. Bradycardia associated with partial atrial standstill was detected and, the patient underwent implantation of a pacemaker at age 77. An echocardiogram revealed marked enlargement of the right atrium and moderate enlargement of the left atrium. Thus, idiopathic enlargement of the right atrium was diagnosed. He had recurrent congestive heart failure before admission to our hospital because of malnutrition and anemia. Although he was treated with high calorie intravenous infusion and blood transfusion, he died of pneumonia and heart failure. Postmortem examination revealed that the heart weighed 430 g, and there was marked dilatation of the right atrium which had an extremely thin wall. The annular circumference of the tricuspid valve was markedly dilated, 170 mm, resulting in tricuspid regurgitation. The left atrium was moderately dilated and the right and left ventricles were slightly dilated. Histologically, the free wall of the right atrium was totally replaced by fibrous tissue and atrioventricular valves did not reveal any rheumatic changes. These pathological findings were compatible with idiopathic enlargement of the right atrium. There has been no previous case report of idiopathic enlargement of the right atrium in a patient aged 80 years of age or over.

Purification by column chromatographies of beta-amyloid precursor proteins and their association with other 95 kDa protein in rat brain.

Beta-amyloid precursor proteins (APPs) in the subcellular fractions of the homogenate of rat brain were detected immunologically. They were found to be localized in both the cytosol and microsome fractions in generally equal amounts. APPs were purified from the cytosol fraction of rat brain by column chromatography in a DEAE-anion-exchanger, Blue-Sepharose, Ni-charged chelating Sepharose, and Sephacryl S-300 columns. They migrated at about 400 kDa or above in a final gel filtration column with trypsin inhibitor activity. They gave two broad protein bands of 80 and 100 kDa and several other protein bands in sodium dodecyl sulfate-polyacryl amide gel electrophoresis (SDS-PAGE). The 80 and 100 kDa bands were highly concentrated during purification. They gave the same amino terminal sequence and were identified as rat APPs without an amino terminal signal sequence. These results suggest that rat brain APPs form a complex with themselves or with other proteins and contain APP isoforms including a serine protease inhibitor domain, APP770 or APP751, or both. An antibody produced by a rabbit immunized with the final preparation of APPs reacted with a 95 kDa protein band which migrated between the 80 and 100 kDa bands of APPs in SDS-PAGE, but it did not react with the bands of APPs. The 80 and 100 kDa APP bands were coprecipitated with a 95 kDa antigen protein band by reacting this antibody with the partially purified APPs. We conclude that APPs in the rat brain are associated directly or indirectly with another protein to yield the 95 kDa band demonstrated by SDS-PAGE.

Detection of Norwalk-like virus genes in the caecum contents of pigs.

Norwalk-like virus genes were detected by RT-PCR in the caecum contents of pigs. Positive PCR products were produced from four out of 1,117 samples by nested PCR using human SRSV primers. Nucleotide sequences between 4,561 and 4,852 numbered according to the Norwalk virus genomic RNA in the RNA polymerase region were determined. Between the Norwalk virus sequence and the sequences detected in pigs, there was 58.2% to 59.9% sequence homology. The swine sequences were located on genogroup II of human SRSVs, but formed a subgroup in the phylogenetic tree of caliciviruses.

Degradation of serum albumin by rat liver and kidney lysosomes.

Lysosomes were isolated from the livers and from the kidneys of rats treated or not treated with the cysteine proteinase inhibitor leupeptin, and the levels of the intralysosomal serum albumin of the leupeptin-treated rats were compared with those of the saline-treated control rats. Leupeptin caused an intralysosomal accumulation of albumin in vivo because of its potent inhibition of lysosomal protein degradation. In fact, the lysosomes isolated from the livers and kidneys of leupeptin-treated rats almost completely lost their ability to degrade rat albumin in vitro. These findings show that the lysosomes are subcellular sites of the degradation of unlabeled serum albumin in these tissues. They also suggest that cysteine proteinases sensitive to leupeptin are involved in the lysosomal degradation of albumin. Albumin was degraded by total lysosomal enzymes in vitro. It was also degraded by the lysosomal extract being devoid of cathepsins H and J, prepared from rat kidney. The degradation of albumin by total lysosomal enzymes in vitro was greatly suppressed by a cysteine proteinase inhibitor, cystatin alpha, with no inhibition of cathepsins B and L. It was slightly suppressed by N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-prol ine (CA-074), a selective inhibitor of cathepsin B, and by pepstatin, an inhibitor of cathepsin D, whereas it was markedly suppressed by a combination of cystatin alpha and either CA-074 or pepstatin. These and associated findings show that cystatin alpha-sensitive cysteine proteinase(s), which is distinct from cathepsins B, H, L, and J, and cathepsins B and D are involved in the lysosomal degradation of albumin.

ATP increases extracellular dopamine level through stimulation of P2Y purinoceptors in the rat striatum.

The effect of ATP on release of dopamine (DA) from rat striatum was studied using in vivo microdialysis. ATP increased the striatal extracellular levels of DA dose-dependently. These analogs produced an increase in DA according to this order of potency: 2-methylthio ATP > ATP > or = alpha,beta-methylene ATP > ADP > AMP > adenosine. Adenosine 5'-[beta, gamma imido]-triphosphate had a more prolonged effect on the increase in DA level than ATP. The ATP-induced increase in DA was inhibited by adding suramin, a nonselective P2 purinoceptor antagonist, and reactive blue 2, a P2Y purinoceptor antagonist, but not inhibited by xanthine amine congener, an adenosine receptor antagonist. Pertussis toxin reduced the increase in DA produced by ATP, which suggests that the P2 purinoceptor may be coupled with a G-protein in the rat striatum. Results suggest that P2Y purinoceptors may involve an ATP-induced increase in DA. The ATP-induced release of DA was tetrodotoxin-sensitive, Ca(2+)-dependent and was abolished by omega-conotoxin GVIA, indicating that the opening of voltage-sensitive Na+ channel and the Ca2+ influx through the N-type voltage-dependent calcium channel are both required for the ATP-induced increase in DA. The ATP-induced increase in DA is presumably due to the release of DA via the stimulation of P2Y purinoceptors in the rat striatum.