Ischemic Brain Changes Research Articles

The Role of Transcranial Grayscale and Doppler Ultrasound Examination in Diagnosis of Neonatal Hypoxic-Ischemic Encephalopathy

Objectives To evaluate role of transcranial grayscale ultrasound (TC-GSUS) and transcranial color Doppler (TCD) in diagnosis of neonatal Hypoxic-ischemic encephalopathy (HIE). Materials & Methods 26 neonates with suspected HIE underwent sonographic examinations using SonoScape SSI-6000 ultrasound device that is equipped by L743 linear array probe with frequency 5-10 MHz. TC-GSUS was performed at levels of anterior, mastoid and posterior fontanelles and at level of temporal window. TCD was performed using Color-coded Doppler study of the intracerebral vessels to assess brain perfusion and detect ischemic brain changes. Resistance index (RI) was considered abnormal in preterm neonates if it was <0.54 or > 0.86 and if it was <0.52 or > 0.8 for term neonates. Results According to cranial biometry, TC-GSUS has negative and positive rates for HIE of 7.7% and 92.3%, respectively. Using TC-GSUS periventricular leukomalacia, intraventricular hemorrhage, brain edema and hydrocephalus were detected in 17, 19, 14 and 16 patients, respectively. According to RI of intracranial vessels, TCD excluded HIE in 11 patients and assured diagnosis of HIE in 15 patients. TC-GSUS can diagnose HIE in neonates with sensitivity, specificity and accuracy rates of 87.5%, 30% and 65.4%, respectively. ROC curve analysis defined abnormally high RI of intracranial arteries as the significant specific predictor for the presence of NHIE and as the significant sensitive predictor for HIE severity grade. Regression analysis defined high RI of internal carotid artery (ICA) as the most specific predictor for presence of HIE, while high RI of anterior cerebral artery (ACA) was the most sensitive predictor for high grade HIE. Conclusion TCD can diagnose HIE in neonates with high sensitivity and specificity and abnormal RI of ICA and ACA could be used as accurate diagnostic tests. Whenever, TCD was unavailable, TC-GSUS could diagnose HIE with accuracy rate of 65.4% versus TCD.

Assessment of Brain Computed Tomography as a Practical Way to Predict Neurological Outcomes in Post-Cardiac Arrest Survivors

Objective: To evaluate whether a visual inspection of ischemic changes in brain computed tomography (CT) images, which is very practical in clinical settings, could predict neurological outcomes in post-cardiac arrest survivors. Materials and Methods: The authors retrospectively reviewed medical records and brain CT images of 62 patients who remained comatose after surviving cardiac arrest and had undergone a CT scan within 24 hours to seven days. Neurological outcomes at one month were assessed using the Cerebral Performance Category (CPC). The CPC scores of 1-2 and 3-5 referred to good and poor neurological outcomes, respectively. Findings from the inspection of the images were graded into grade 1 for absence of acute ischemic change, grade 2 for decreased attenuation of the grey matter in some brain region(s), and grade 3 for diffused loss of grey-white matter differentiation or apparent brain swelling. An experienced neurologist and a consensus group of four pre-clerkship medical students, blinded to the neurological outcomes, evaluated the grade of ischemic changes in CT images. Results: Positive correlations were observed between CPC and CT grading by both the neurologist (ρ=0.76, 95% CI 0.63 to 0.90, p<0.001) and medical students (ρ=0.57, 95% CI 0.38 to 0.77, p<0.001). The CT grading of 2 or more by the neurologist could predict poor neurological outcomes with specificity of 1.00, sensitivity of 0.89, and receiver operating characteristic (ROC) AUC of 0.94 (95% CI 0.89 to 1.00). The evaluation by medical students showed an ROC AUC of 0.80 (95% CI 0.64 to 0.96). Conclusion: The simple visual inspection of ischemic changes in brain CT images showed a high diagnostic accuracy and could be a practical method for predicting neurological outcomes in post-cardiac arrest survivors. Keywords: Cardiac arrest; Post-cardiac arrest ischemic brain injury; Neurological outcomes; Computerized tomography

Phagocytosis converts infiltrated monocytes to microglia-like phenotype in experimental brain ischemia

BackgroundMonocyte-derived macrophages (MDMs) and microglia elicit neural inflammation and clear debris for subsequent tissue repair and remodeling. The role of infiltrating MDMs in the injured brain, however, has been controversial due to overlapping antigen expression with microglia. In this study, we define the origin and function of MDMs in cerebral ischemia.MethodsUsing adoptive transfer of GFP+ splenocytes into adult asplenic mice subjected to transient middle cerebral artery occlusion, we compared the role of CD11b+/CD45+/NK1.1−/Ly6G− MDMs and microglia in the ischemic brain. The phagocytic activities of MDMs and microglia were measured by the uptake of fluorescent beads both in vivo with mice infused with GFP+ splenocytes and ex vivo with cultures of isolated brain immune cells.ResultsStroke induced an infiltration of MDMs [GFP+] into the ipsilateral hemisphere at acute (3 days) and sub-acute phases (7 days) of post-stroke. At 7 days, the infiltrating MDMs contained both CD45High and CD45Low subsets. The CD45High MDMs in the injured hemisphere exhibited a significantly higher proliferation capacity (Ki-67 expression levels) as well as higher expression levels of CD11c when compared to CD45Low MDMs. The CD45High and CD45Low MDM subsets in the injured hemisphere were approximately equal populations, indicating that CD45High MDMs infiltrating the ischemic brain changes their phenotype to CD45Low microglia-like phenotype. Studies with fluorescent beads reveal high levels of MDM phagocytic activity in the post-stroke brain, but this phagocytic activity was exclusive to post-ischemic brain tissue and was not detected in circulating monocytes. By contrast, CD45Low microglia-like cells had low levels of phagocytic activity when compared to CD45High cells. Both in vivo and ex vivo studies also show that the phagocytic activity in CD45High MDMs is associated with an increase in the CD45Low/CD45High ratio, indicating that phagocytosis promotes MDM phenotype conversion.ConclusionsThis study demonstrates that MDMs are the predominant phagocytes in the post-ischemic brain, with the CD45High subset having the highest phagocytic activity levels. Upon phagocytosis, CD45High MDMs in the post-ischemic brain adopt a CD45Low phenotype that is microglia-like. Together, these studies reveal key roles for MDMs and their phagocytic function in tissue repair and remodeling following cerebral ischemia.

Contrast-enhanced encephalopathy and massive cerebral edema after endovascular coiling of cerebral aneurysm. A case report

Contrast-induced encephalopathy (CIEP) is a rare complication after endovascular therapy. The etiology of CIEP is still a matter of debate. We present a rare occurrence of CIEP in a known hypertensive and type 2 diabetic patient after endovascular coiling of cerebral aneurysm with oculomotor nerve palsy. A 68-year old female presented with seven days history of headache and left ptosis or blepharoptosis with mild mydriasis. The headaches were localized mainly at the left side of the nose, orbit, and upper forehead while the left ptosis was associated with blurred vision. Computed tomography angiography revealed an aneurysm in between the C4 segment of the left internal carotid artery (ICA) and the bifurcation of the left posterior communicating artery. Digital subtraction angiography further confirmed the aneurysm. We used the transarterial approach to assess the aneurysm and subsequent coiling. Iohexol (Omnipaque) contrast agent was used during the endovascular procedure. The patient’s condition deteriorated into acute confusion state with cardinal symptomology of CIEP immediately after the operation. Computed tomography scan revealed cortical contrast enhancement in the vascular territory of the ICA as well as edema. Her symptomatology resolved 48 hours after treated with anticonvulsants, intracranial pressure reduction and hydration. Chronic hypertension as well as type 2 diabetics may be critical predisposing factors to CIEP. CIEP should be suspected in patients presenting with acute confusion state after endovascular therapy. Massive edema with ischemic brain changes in white matter of the brain before endovascular procedure should rise suspicion of CIEP.

Ischaemic brain changes associated with catheter-based diagnostic cerebral angiography: a diffusion-weighted imaging study.

PurposeThis study aims to evaluate the incidence of clinically silent embolic cerebral infarctions and associated risk factors following diagnostic cerebral angiography with diffusion-weighted imaging (DWI).Material and methodsA total of 71 cerebral digital subtraction angiograms (42 male, 29 female, average age: 56.0 ± 15.0) obtained using nonionic contrast material were prospectively evaluated. To assess embolic events, before and after (1-3 days) angiography, DWI was performed. The risk factors for embolic ischemic brain changes such as the patient’s age and sex, atherosclerotic vessel wall disease, type of indication for catheter angiography, the number and size of the catheters, anatomic variants, selective/nonselective catheterization, contrast media volume, and time of procedure were determined. Fisher’s exact tests and Student t-tests were used for the statistical analyses of outcomes.ResultsThirteen new silent ischemic lesions were identified in 7 out of 71 patients who underwent diagnostic cerebral angiography. Embolic cerebral lesions were often 6-10mm in diameter. According to the findings in this study, there was a strong correlation between diffusion abnormality and patient age, which was considered risk factors (p < 0.05). However, there were no significant correlations between other risk factors and the lesions’ appearance (p > 0.05).ConclusionsIn elderly patients, the angiographic procedures should be performed meticulously and DWI in all patients obtained routinely, even if the regular neurological examination shows they are healthy. In this way, the presence of microemboli and clinical results can be evaluated.

Cognitive function dynamics in comorbid patients after angioreconstructive interventions

Angioreconstructive interventions are generally known to be of prophylactic value for cerebrovascular diseases (CVD). At the same time, their prognosis in comorbid patients, particularly in those with type 2 diabetes (T2D), have been insufficiently covered.Objective: to study the impact of T2D on cognitive functions after carotid angioplasty with stenting (CAS)Patients and methods. CAS was performed in 99 patients with chronic CVD. Group 1 consisted of 51 patients (median age, 64.5 years) without carbohydrate metabolism disorders. Group 2 included 48 patients (median age, 64 years) with T2D. Over time, all the patients underwent clinical, neurological, and neuropsychological examinations, general clinical and biochemical blood tests, duplex scanning of the brachiocephalic arteries, and magnetic resonance imaging (MRI) of the brain. Blood flow in the middle cerebral artery was monitored to assess the embolic and hemodynamic situation during a CAS procedure.Results and discussion. The baseline frequency of neurocognitive impairment was almost the same (75%) in both groups; however, the impairment was more obvious in patients with T2D. Re-examination in Group 1 patients immediately after intervention revealed slight positive cognitive changes, while the patients with T2D showed a decrease in the indicators of mental functions. The improved ability to abstract and increase the level of generalization of functions appeared in T2D patients only 2 months after intervention. Post-CAS MRI revealed ipsilateral acute ischemic foci (AIF) in the brain substance in 11 (22%) patients of Group 1 and in 24 (50%) with concomitant T2D. Comparison of neuroimaging data with cognitive function assessments for the entire group of the examinees established deterioration in the cognitive status in patients with new ischemic brain changes detected after intervention.Conclusion. CVD concurrent with T2D usually contributes to deterioration in the cognitive status. Angioreconstructive interventions, in particular CAS, are frequently accompanied by the identification of AIF (including «silent» ones) that can cause a transient deterioration in cognitive functions. When planning angioreconstructive interventions in patients with T2D, the question arises of predicting such risks and possible neuroprotective methods.

Evaluation of frequency-selective non-linear blending technique on brain CT in postoperative children with Moyamoya disease

ObjectiveTo evaluate whether a frequency-selective non-linear blending (BC) technique can improve tissue contrast and infarct detection on non-enhanced brain CT (NECT) in postoperative Moyamoya (MMD) patients. Materials and methodsFrom January 2010 to December 2017, 33 children (13boys and 20girls; mean age 9.1±3.4 years) with MMD postoperatively underwent NECT followed by diffusion MRI. We compared the contrast-to-noise ratio (CNR) between gray matter (GM) and white matter (WM) in NECT and BC images and the CNR between the infarct lesion and adjacent normal-appearing brain in NECT and BC images using a paired t-test. We assessed image noise, GM-WM differentiation, artifacts, and overall quality using a Wilcoxon signed rank test. A McNemar two-tailed test was conducted to compare the diagnostic accuracy of infarct detection. ResultsThe CNR between GM and WM and the CNR of the infarct was better in BC images than in NECT images (3.9±1.0 vs. 1.8±0.6, P<0.001 and 3.6±0.3 vs. 1.9±0.2, P<0.001), with no difference in overall image quality observed. The sensitivity and specificity of infarct detection were 55.0% and 76.9% using NECT, and 70.0% and 69.2% using BC technique. The diagnostic accuracy of NECT and BC technique was 63.6% (21/33) and 69.7% (23/33), respectively. ConclusionThis study showed that the BC technique improved CNR and maintained image quality. This technique may also be used to identify ischemic brain changes in postoperative MMD patients by improving the CNR of the infarct lesion.

Dose reduction in perfusion CT in stroke patients by lowering scan frequency does not affect automatically calculated infarct core volumes

Background and purposeCT Perfusion technique (CTP) is a quantitative, easily performed, accepted and reliable method for detection of ischemic brain changes. Based on calculated parameters, the size of ischemic penumbra and irreversibly damaged infarct core can be determined which helps guide treatment decisions. However, due to the dynamic nature of the CTP study, it is dose intensive. This study determines the consequences of retrospectively reducing the number of scans in the dynamic acquisition by half on the volume of the automatically calculated infarct core (non-viable tissue) and penumbra (tissue at risk) volumes. Our hypothesis was that equivalent volumetric information could be obtained at a substantial dose savings. Materials and methodsFifty one consecutive patients with occlusion of M1 and/or M2 segment of the middle cerebral artery and ischemic stroke proven by follow-up MRI were included. CTP scans were first analyzed in a standard fashion and automatically generated volumes measured in milliliters were recorded in a database. A second analysis was conducted after removing every second data acquisition from the sequential CTP scans. Automatic volume measurements were repeated, recorded and compared to the initial values obtained using the full dataset. ResultsThe two CTP protocols were statistically equivalent pertaining to automatic infarct core volume calculation but a case-by-case analysis revealed substantial overestimation in some cases. ConclusionReduction of radiation exposure in CTP without objective loss of accuracy of automatically calculated infarct core volume is feasible but might lead to clinically relevant infarct core overestimation in individual cases.

Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort.

ObjectiveThe effect of serum autoantibodies on the brain of systemic lupus erythematosus (SLE) patients remains unclear. We investigated whether serum autoantibodies, individually and assessed in groups, are associated with specific brain-MRI abnormalities or whether these structural changes are associated with other SLE-related or traditional cardiovascular disease risk factors.MethodsAll patients underwent brain 3Tesla-MRI. White matter hyperintensities (WMHs), ischemic lesions, inflammatory-like lesions and cerebral atrophy were scored. Serum autoantibodies analyzed included lupus anticoagulant (LAC), anticardiolipine (aCL) IgG and IgM (first 3 also grouped into antiphospholipid autoantibodies (aPL)), anti-dsDNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm (the latter 5 grouped into SLE-related autoantibodies). Associations were assessed using logistic regression analysis adjusted for potential confounders. Furthermore, a sensitivity analysis including anti-Beta2 glycoprotein-1 antibodies (anti-β2GP1) in the aPL group was performed and the potential modification role of the neuropsychiatric clinical status in the model was assessed.Results325 patients (mean age 42 years (SD 14), 89% female) were included. The following MRI-brain abnormalities were found: WMHs (71%), lacunar infarcts (21%), gliosis (11%), micro-hemorrhages (5%), large hemorrhages (2%), inflammatory-like lesions (6%) and atrophy (14%). No associations were found between individual or total SLE-related autoantibodies and inflammatory-like lesions. A higher number of positive aPL was associated with lacunar infarcts (OR 1.37 (95%CI 1.02–1.99) and gliosis (OR 2.15 (1.37–3.37)). LAC was associated with lacunar infarcts in white matter (OR 3.38 (1.32–8.68)) and atrophy (OR 2.49 (1.01–6.15)), and aCL IgG with gliosis (OR 2.71 (1.05–7.02)). Among other variables, SLE patients with hypertension presented a higher chance for WMHs (OR 5.61 (2.52–12.48)) and lacunar infarcts in WM (OR 2.52 (1.10–5.74)) and basal ganglia (OR 8.34 (2.19–31.70)), while cumulative SLE-damage was correlated with lacunar infarcts in WM (OR 1.43 (1.07–1.90)), basal ganglia (OR 1.72 (1.18–2.51)) and cerebellum (OR 1.79 (1.33–2.41)). These associations were confirmed in the sensitivity analysis.ConclusionsBrain abnormalities in SLE represent different underlying pathogenic mechanisms. aPL are associated with ischemic brain changes in SLE, while the presence of SLE-related serum autoantibodies is not related to inflammatory-like lesions. Hypertension and cumulative SLE-damage associate with ischemic MRI-brain changes in SLE, suggesting the importance of accelerated atherosclerosis in this process.

Association Between Endogenous Testosterone and Cerebrovascular Disease in the ARIC Study (Atherosclerosis Risk in Communities).

Epidemiological studies in men suggest a relationship between endogenous testosterone and ischemic vascular events. We hypothesized that low testosterone is independently associated with ischemic stroke and ischemic brain changes. In 1558 male participants (mean [SD] age, 63.1 [5.6] years; body mass index, 28.2 [4.3] kg/m2) from visit 4 (1996-1998) of the ARIC study (Atherosclerosis Risk in Communities) without cardiovascular disease, stroke, and previous testosterone therapy, we measured plasma total testosterone by liquid chromatography mass spectrometry using morning samples and divided levels into tertiles (median [25th-75th percentile], 377.6 [288.4-480.1] ng/dL). General linear models, for cross-sectional analyses, and proportional hazards regression, for time-to-event analysis, examined the association of testosterone with participant characteristics and incident stroke through 2011. Linear and logistic regression models examined the association of testosterone with percentage white matter hyperintensities and prevalent infarcts in participants (n=257) who underwent brain magnetic resonance imaging at visit 5 (2011-2013). Analyses were adjusted for age, race, and ARIC center, body mass index, waist circumference, smoking status, diabetes mellitus, hypertension, low-density lipoprotein, and high-density lipoprotein. Lower testosterone was significantly associated with higher body mass index, greater waist circumference, diabetes mellitus, hypertension, lower high-density lipoprotein, and never smoking. After adjustment, no association of testosterone with incident stroke was found (hazard ratios [95% confidence intervals] for tertile 1 or 3 versus 2, 1.47 [0.83-2.61], 1.15 [0.62-2.14]; median follow-up, 14.1 years), nor with percentage white matter hyperintensities, cortical infarcts, or subcortical infarcts. After controlling for atherosclerotic risk factors, there was no association between endogenous testosterone and incident clinical stroke or ischemic brain changes in community-dwelling men.

Migraine and cerebral blood flow in the general population.

Observations that migraine increases risk of cardiovascular disease and ischemic brain changes may suggest sustained vascular differences between migraineurs and controls. In a population-based setting, we compared cerebral blood flow between migraineurs in the attack-free period and controls. Between 2006 and 2008, 2642 participants, aged 45-65, from the Rotterdam Study completed a migraine questionnaire and had complete usable MRI data. Participants were classified into controls (N = 2033), probable migraine (N = 153), or migraine (N = 456). Using 2D phase contrast MRI, we performed a cross-sectional analysis of the effect of migraine on total cerebral blood flow (tCBF), parenchymal cerebral blood flow (pCBF), and blood flow in each intracranial arterial using linear regression. Additionally, we performed stratified analysis of subtypes of migraine. Compared with controls, migraineurs had higher pCBF (1.07 ml/min/100 ml, 95% CI 0.08; 2.05). In particular, migraineurs had significantly higher blood flow in the basilar artery (4.70 ml/min, 95% CI 0.77; 8.62). Migraineurs in the attack-free period have higher pCBF, particularly basilar artery flow, compared to controls, supporting the notion of sustained vascular differences between these groups outside of migraine attacks.

Paroxysmal Nocturnal Hemoglobinuria and Magnetic Resonance Imaging

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and complex disease characterized by a severe prothrombotic state caused by a complement system mediated hemolysis. The introduction of the anti-C5 antibody, Eculizumab, has been conducted in many Hematology units worldwide to adopt new diagnostic tools to evaluate new and old PNH patients in order to consider the adequacy of the adoption of this new drug in each case.Magnetic Resonance Imaging (MRI) allows a more adequate and profitable approach in PNH that other radiology techniques used for this purpose. In the last four years Hematology and Radiology units in our Hospital have collaborate in the clinical evaluation of PNH patients performing MRI (cranioencephalic, thoracic and/or abdominal) in acute complications of PNH patients (9 patients) or as a programmed protocoled evaluation previous to consider Eculizumab treatment (14 patients).The protocoled evaluation consists in thoracic and abdominal MRI evaluations in all cases, and cranioencephalic MRI (with independence of the presence of neurological symptoms) in 9 cases. The PNH patients were examined with 1.5 Teslas magnet for cranioencephalic,thoracic and abdominal MRI and with 3.0 Teslas magnet for some cranioencephalic MRI (Achieva Magnets; Philips Healthcare, Best, The Netherlands).Different protocols designed for the study of this pathology, using morphological sequences with different empowerment, functional sequences and angiographic studies after administration of intravenous contrast (gadobutrol) have been used. In the abdominal explorations had been performed calculations of T2 * for the quantification of deposit of iron in liver and kidney.The first group of patients (incidental studies in acute/chronic situations) included Classical and with other bone marrow failure syndrome (BMFS) Parker's types. The second group (protocoled studies previous consideration of Eculizumab therapy) consisted on 11 Classical Parker's type patients with active hemolysis (LDH increased 3-13 times over normal levels) and elevated PNH clone (73-99% negative GPI granulocytes by FLAER cytometry); and 3 with BMFS Parker's type patients (LDH increased 2-6 times over normal levels) with lower PNH clone (43-50% negative GPI granulocytes by FLAER cytometry). Thrombosis was found in four cases, one in the inferior cava and and three arterial (two cerebral and one in descendent aorta). In three patients this finding implied to initiate Eculizumab therapy. Minor ischemic brain changes were displayed by three patients. None of the eighteen patients explored with thoracic MRI, displayed pulmonary hypertension signs despite the elevation of pro-BNP in eight of them. Iron overload in the liver and/or kidneys were very frequent. The finding of a reversal of the normal cortical and medullary intensities on T1 and T2 weighted images of both kidneys was evident in the majority of patients with severe PNH types. Interestingly, one patient with a chronic PNH severe form displayed no renal iron cortical after two years on Eculizumab therapy. This finding was also evident in patients with active hemolysis in the past but with very low PNH clones and clinical remission of the disease.Many other incidental discoveries includes cholelithiasis, splenomegaly, kidney arterial vessel constriction, vascular anomalies, kidney and vesical stones, adrenal adenoma, atheromatosis at different levels, Tornwaldt cyst, hamartoma, hemangiomas and abnormal bone marrow signal.MRI is the best imaging technique to diagnose thrombosis in PNH patients and to control evolution. Moreover, in the cerebrovascular setting allows a more fine and precise diagnosis of the minor pathologic thrombotic changes. MRI is the only imaging technique that permits to evaluate the iron overload that in some PNH cases could be underestimated and needs quelation therapy. In our opinion all new patients with classical severe hemolytic PNH must be evaluated prospectively with MRI. The collaboration of the Radiology team with the Hematologist is fundamental to acquire expertise in this rare disease. Disclosures:Pastrana:Alexion Pharmaceuticals: Speakers Bureau. Ojeda:Alexion Pharmaceuticals: Consultancy, Speakers Bureau.

Cerebral microbleeds detected on T2-weighted gradient echo magnetic resonance and its clinical significance

To explore the diagnostic value of T2-weighted gradient-echo magnetic resonance imaging (MRI) in cerebral microbleeds (CMBs) and its clinical significance. The distribution of CMBs and follow-up observations were performed by routine T1WI, T2WI and T2-weighted gradient echo sequence in 634 patients clinically suspected for stroke. In 149 patients, a total of 1140 CMBs occurred predominantly in cortex-subcortical area (n = 471, 41.31%), basal ganglia (n = 289, 25.35%), thalamus (n = 199, 17.45%), brain stem (n = 90, 7.89%) and cerebellum (n = 91, 7.98%). Among them, 137 patients had various degrees of ischemic brain changes, displayed iso-intensity or hypo-intensity on T1WI, hyper-intensity on T2WI and FLAIR in basal ganglia, white matter around sided ventricle and brain stem. There were 23 patients with cerebral infarction and 5 with CMBs after hemorrhagic brain stroke. And 12 of them had new hemorrhagic stroke in 2-6 months. T2-weighted gradient echo MRI has obvious advantages in the detection of CMBs. The presence of CMBs suggests a risk of cerebral hemorrhage.

Cognitive function and retinal and ischemic brain changes

To examine the association between retinopathy and cognitive decline or brain lesions and volumes in older women. This study included 511 women aged 65 and older who were simultaneously enrolled in the Women's Health Initiative Memory Study and the Sight Examination Study. In this analysis, we examined the link between retinopathy, assessed using fundus photography (2000-2002), cognitive performance over time assessed by the modified Mini-Mental State Examination (3MSE) (1996-2007), and white matter hyperintensities and lacunar infarcts in the basal ganglia. Presence of retinopathy was associated with poorer 3MSE scores (mean difference = 1.01, SE: 0.43) (p = 0.019) over a 10-year follow-up period and greater ischemic volumes in the total brain (47% larger, p = 0.04) and the parietal lobe (68% larger, p = 0.01) but not with measures of regional brain atrophy. The correspondence we found between retinopathy and cognitive impairment, along with larger ischemic lesion volumes, strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes. Retinopathy may be useful as a clinical tool if it can be shown to be an early marker related to neurologic outcomes.

EFFECT OF MORPHINE WITHDRAWAL SYNDROME ON CEREBRAL ISCHEMIA OUTCOME IN RATS

Objective(s) Opioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes. Materials and Methods Addiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA). Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke. Results Morphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05) at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05). Conclusion Our data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

Diffusion- andT2-Weighted Increases in Magnetic Resonance Images of Immature Brain during Hypoxia–Ischemia: Transient Reversal Posthypoxia

Hypoxic–ischemic changes in brain are detected earlier with diffusion-weighted (DW) than withT2-weighted magnetic resonance (MR) imaging techniques in adults, whereas the response in immature brain is not known. We investigated MR imaging changes prior to, during, and/or after 2 h of hypoxia–ischemia (right carotid artery occlusion+2 h of hypoxia) in 7-day-old rats anesthetized with isoflurane. In general, within the first 45 min of hypoxia–ischemia there were no changes in the DW orT2-weighted images. By the second hour of hypoxia–ischemia there were marked areas of increased intensity inboththeT2and the DW images, with cortex and striatum being affected prior to thalamus and hippocampus. The area of DW exceeded that ofT2hyperintensities. In the first hour after hypoxia–ischemia there was a transient recovery of hyperintensities on bothT2and DW images. Between 24 and 72 h the hyperintense area on DW images decreased, whereas that onT2-weighted images increased. The distribution of pathological damage assessed histologically correlated with the areas of hyperintensity on the MR images. In contrast to adult brain, early hypoxic–ischemic injury in immature brain is detected as an increase in intensity in both diffusion-and T2-weighted images, indicating a unique alteration in brain water dynamics in this neonatal model of hypoxia–ischemia. These imaging changes and alterations in brain water can rapidly but transiently reverse upon the start of normoxia and reperfusion, suggestive of secondary energy failure or delayed neuronal death.

PATHOLOGY AND PATHOGENETIC MECHANISMS IN NEUROTUBERCULOSIS

The mechanisms and the changes described herein typically begin with a dense basal meningeal exudate often resulting from a "Rich focus" along the basal surface of the cerebrum or ventricular ependyma. In the interpeduncular fossa, when the exudate is copious, among other structures the proximal parts of the optic nerves and of the internal carotid arteries are seen surrounded and compressed by the exudate. This exudate is made up of small and large mononuclear cells, including epithelioid cells, which also act as macrophages and may fuse to form Langhans' giant cells. Further extension of this exudate along small proliferating blood vessels into the brain substance constitutes a border zone encephalitis with the development of focal and diffuse ischemic brain changes due to vasculitis. Entrapment and occasional arteritic occlusion of larger arteries, such as the middle cerebral in the Sylvian fissures, results in infarction. Blockage of the basal subarachnoid cisterns around the midbrain and pons by the dense basal exudate or narrowing of aqueduct and third ventricle by a small tuberculoma causes consequent hydrocephalus. Development of many or one large focal granuloma (i.e., tuberculoma) occurs in the cerebrum, cerebellum, and/or brain stem. Similar pathogenetic mechanisms produce tuberculous spinal meningitis myeloradiculopathy that may be secondary to or occur before cranial tuberculous meningitis. More extensive damage to the white matter may occur together with the infrequent onset of perivascular demyelination on the basis of a hypersensitivity reaction to tuberculoprotein (i.e., "allergic tuberculous encephalopathy"). Finally, there may be a part played by NO in the production of the vascular and perivascular inflammatory central nervous system changes and a role for the the potential beneficial action of corticosteroids, especially in cases of tuberculous encephalopathy.

慢性腎透析と脳血管障害

Recently, the age of patients receiving chronic hemodialysis has markedly increased and diabetic nephropathy in aged subjects is often induced by dialysis. Consequently, many aspects of the patterns and features of cerebrovascular diseases complicated by dialysis are changing.1. Cerebral hemorrhage in chronic dialysis patients are more frequent and more severer than in non-dialysis subjects or the general population. Subcortical hemorrhage, is more frequently seen in dialytics, the cause of which is unknown. However, in aged persons, amyloid degeneration of the cerebral arteries is common, so cerebral hemorrhage due to amyloid angiopathy must be cautiously checked, although we have no clinical method of detecting amyloid angiopathy in daily practices.The incidence of cerebral hemorrhage in dialytics has decreased in recent years, perhaps due to effective control of hypertension and improvement of dialysis techniques, but the frequency of cerebral infarction may increase again. Pathogenesis of cerebral hemorrhage in dialytics is discussed.2. In a cranial MRI study on 71 dialysis patients without cerebrovascular signs and symptoms, ischemic changes were classified into cerebral white matter lesions, lacunes and brain stem infarctions.a) Ischemic brain changes on MRI were found in 38 subjects (53.5%), but cerebral hemorrhage was found in only 1 patient (1.4%). In the remaining 32 (45.1%), there were no abnormal images. Ischemic lesions on MRI were found more than half of the dialysis subjects and increased with advancing age; above 70 years of age, practically all patients showed ischemic changes on MRI imaging. The frequency of brainstem lesions showed no age-difference. Lacunes were reduced after middle-age, while cerebral white matter lesions increased linearly with advancing age. Although asymptomatic cerebral lesions were found in many of dialysis patients, whether they were really “asymptomatic” or not, is an important issue. Psychiatric evaluations are needed in dialysis patients, because depression or other psychiatric manifestations are not rare in these subjects.3. Six dialysis patients with cerebral hemorrhage or cerebral infarction verified on MRI and/or at autopsy are presented. A 47-year-old male patient with autosomal dominant polycystic kidney disease (PKD) showed a massive cerebral hemorrhage in the putaminal region. Intracranial aneurysms were not found in this patient. Genetic relationship in autosomal dominant PKD is discussed, especially in relation to collagen genes.4. Incidental cerebral aneurysms were found in 88 subjects aged sixty years or more among 1, 200 non-selected routine autopsies. Rupture occurred in 17% of all aneurysms, while fatal ruptures were found in 78% of aneurysms more than 6mm in diameter. MRI imaging is necessary in cases of dialysis to find silent cerebral aneurysms, the rupture of which may often be fatal.5. Subdural hematoma (SDH) are not rare in dialysis patients. We must remain alert to this disorder, because SDH is apt to be misinterpreted in dialysis patients.6. We propose that a liason of therapists including internal medicine, neurology, neurosurgery or orthopedics should be organized for prevention and management of cerebrovascular lesions in chronic dialysis.

Rethinking Vascular Dementia (Part 2 of 2)

Vascular dementia is growing in importance, so is the confusion surrounding it. Vascular dementia may be regarded as a syndrome of cognitive impairment resulting from vascular diseases, especially ischemic brain changes. It may be related to many different vascular mechanisms, types of brain changes and risk factors. However, currently no precise knowledge exists regarding the extent to which these factors cause, contribute or only coincide with the cognitive loss. The resulting imprecision in definition and diagnosis breeds confusion regarding prevention, treatment and incidence of the syndrome. In addition, the changing patterns of age of the population, risk factors and types of stroke complicate the clinical picture. Instead of comfortable categorization, the emphasis needs to be shifted to identifying and understanding the interactive vascular factors that contribute to cognitive impairment. This may open avenues in the search for modifiable and treatable vascular components.

Rethinking Vascular Dementia (Part 1 of 2)

Vascular dementia is growing in importance, so is the confusion surrounding it. Vascular dementia may be regarded as a syndrome of cognitive impairment resulting from vascular diseases, especially ischemic brain changes. It may be related to many different vascular mechanisms, types of brain changes and risk factors. However, currently no precise knowledge exists regarding the extent to which these factors cause, contribute or only coincide with the cognitive loss. The resulting imprecision in definition and diagnosis breeds confusion regarding prevention, treatment and incidence of the syndrome. In addition, the changing patterns of age of the population, risk factors and types of stroke complicate the clinical picture. Instead of comfortable categorization, the emphasis needs to be shifted to identifying and understanding the interactive vascular factors that contribute to cognitive impairment. This may open avenues in the search for modifiable and treatable vascular components.