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Background: Circulating endothelial cells (CECs) are a novel and valuable marker of endothelial damage in a variety of vascular disorders. There is limited information as to CEC counts and the time course of CECs in subtypes of stroke., Methods: We studied 49 patients with stroke (18 with atherothrombotic infarction in the territory of the middle cerebral artery, 16 with cardioembolic stroke, and 15 with lacunar stroke). We also included 16 healthy controls and 64 disease controls. CECs were isolated and enumerated with lectin-augmented CD146-driven immunomagnetic isolation. Neurologic deficit was assessed with the European Stroke Scale (ESS) and the National Institutes of Health Stroke Scale (NIHSS). Recovery was assessed with the modified Rankin scale (mRS)., Results: Healthy controls had low numbers of CECs (median, 8 cells/mL; mean, 9 cells/mL; range, 0-16 cells/mL; n = 16). Patients with stroke had markedly elevated numbers of CECs at presentation. Patients with atherothrombotic infarction had 32 cells per milliliter (mean, 42 cells/mL; range, 24-116 cells/mL; n = 18; P < .001 when compared to controls). Patients with lacunar stroke had 68 cells per milliliter (mean, 68 cells/mL; range, 8-144 cells/mL; n = 15; P < .001 when compared to controls). Patients with cardioembolic stroke had 46 cells per milliter (mean, 54 cells/mL; range, 24-116 cells/mL; n = 16; P < .001 when compared to healthy controls). There was a tendency towards higher numbers of CECs in lacunar stroke. The number of CECs peaked at day 7 in patients with atherothrombotic infarction and came back to normal at day 90. In contrast, CECs in patients with acute lacunar stroke and cardioembolic stroke decreased progressively until day 90., Conclusions: CECs are markers of endothelial damage and/or repair in stroke. Differences during the course of disease are likely to reflect different pathophysiology., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Increased blood-brain barrier (BBB) permeability for ammonia is considered to be an integral part of the pathophysiology of hepatic encephalopathy (HE) in patients with liver cirrhosis. Increased glutamate-/glutamine-signal intensity in magnetic resonance spectroscopic studies of the brain in cirrhotic patients was explained as a consequence of increased cerebral ammonia uptake. As similar spectroscopic alterations are present in patients with liver fibrosis, we hypothesized that BBB permeability for ammonia is already increased in liver fibrosis, and thereby contributing to the development of HE. To test this hypothesis, cerebral perfusion and ammonia metabolism were examined through positron emission tomography with (15)O-water, respectively, (13)N-ammonia in patients with Ishak grades 2 and 4 fibrosis, cirrhosis, and healthy controls. There were neither global nor regional differences of cerebral blood flow, the rate constant of unidirectional transport of ammonia from blood into brain tissue, the permeability surface area product of the BBB for ammonia, the net metabolic clearance rate constant of ammonia from blood into glutamine in brain, or the metabolic rate of ammonia. The hypothesis that increased permeability of the BBB for ammonia in patients with liver fibrosis contributes to the later development of HE could not be supported by this study.

Introduction: The aim of our study was to evaluate the safety and efficacy of intra-arterial (IA) thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute stroke due to occlusion in the anterior or posterior circulation., Methods: We retrospectively analyzed the clinical and radiological data of 88 consecutive patients with acute ischemic stroke who underwent emergency cerebral angiography for the purpose of subsequent IA thrombolysis. The neurological deficit on admission and discharge was graded using the National Institutes of Health Stroke Scale (NIHSS) score. Baseline computer tomography (CT) scans were examined for any signs indicative of cerebral ischemia. The angiographic findings were classified according to the Thrombolysis in Myocardial Infarction (TIMI) score for myocardial infarction. Follow-up CT scans were examined for hemorrhagic complication., Results: Of the 88 patients who underwent IA thrombolysis, 63 presented with complete or partial arterial occlusion in the suspected perfusion area. In these 63 patients, the median NIHSS score dropped from 15 points on admission to 10 points at discharge. The recanalization rate was 52.6% for partial and complete reperfusion. In-hospital mortality was 20.6% (9.1% for carotid, 44.4% for basilar territory occlusion). Intracerebral bleeding (ICB) occurred in 38.6% of the patients with occlusion in the anterior circulation, resulting in these patients presenting a worse clinical outcome than those without ICB. Only minor extracranial bleedings occurred in 20.6% of patients. Patients with ICB had a significantly higher frequency of ischemic signs on the baseline CT scan., Conclusion: Occlusion of a cerebral artery is present in about 75% of the patients eligible for thrombolytic therapy. Intra-arterial thrombolysis using rt-PA in patients with acute ischemic stroke can achieve re-vascularization, although ICB remains the major risk factor affecting its efficacy.

Background/aims: Bradykinesia is one of the first symptoms of hepatic encephalopathy (HE). Recently it has been suggested that bradykinesia in HE is due to disturbances in movement initiation. Areas involved in self-initiated movement are the motor- and premotor cortex, the supplementary motor cortex, the motor areas of the cingulate gyrus, and part of the frontomesial- and parietal cortex. The present study aimed to test the hypothesis that bradykinesia in HE is due to a functional disturbance of these areas., Methods: Fourteen cirrhotics with grade 0-I HE were examined. Patients with alcoholic cirrhosis or concomitant cerebral disorder were excluded. Patients underwent a 3-dimensional computer-assisted movement analysis for forearm pronation and supination, hand tapping and finger tapping and a (18)F-fluorodesoxy-glucose-PET-examination during rest, analysed with statistical parametric mapping (SPM99)., Results: The frequency of finger- and hand tapping was significantly correlated to the glucose metabolism of the motor area of the cingulate gyrus and frontomedial, frontodorsal and parietal cortical areas known to be activated with self-initiated movements. A decrease of movement frequency was associated with a reduction of glucose metabolism within these areas., Conclusions: These data support the hypothesis that bradykinesia in cirrhotics with HE is caused by an alteration of movement initiation.

Twelve patients with ICA stenosis underwent dynamic perfusion computed tomography (CT) and positron emission tomography (PET) studies at rest and after acetazolamide challenge. Cerebral blood flow (CBF) maps on perfusion CT resulted from a deconvolution of parenchymal time-concentration curves by an arterial input function (AIF) in the anterior cerebral artery as well as in both anterior choroidal arteries. CBF was measured by [(15)O]H(2)O PET using multilinear least-squares minimization procedure based on the one-compartment model. In corresponding transaxial PET scans, CBF values were extracted using standardized ROIs. The baseline perfusion CT-CBF values were lower in perfusion CT than in PET (P>0.05). CBF values obtained by perfusion CT were significantly correlated with those measured by PET before (P<0.05) and after (P<0.01) acetazolamide challenge. Nevertheless, the cerebrovascular reserve capacity was overestimated (P=0.05) using perfusion CT measurements. The AIF selection relative to the side of carotid stenosis did not significantly affect calculated perfusion CT-CBF values. In conclusion, the perfusion CT-CBF measurements correlate significantly with the PET-CBF measurements in chronic carotid stenotic disease and contribute useful information to the evaluation of the altered cerebral hemodynamics.

Deficits in attention and arousal play a major role in the clinical presentation of hepatic encephalopathy. Attention deficits are also the main components of minimal hepatic encephalopathy. The present paper summarizes some findings about attentional and memory dysfunction in hepatic encephalopathy, with reference to basic knowledge about normal attention and memory function and their cerebral representation.

The clinical presentation of acute liver failure and hepatic encephalopathy (HE) in patients with cirrhosis differs significantly. The most serious neurological complication of acute liver failure is the development of devastating brain oedema. Therefore, intracranial pressure monitoring is urgently needed in these patients. Brain oedema is amplified by hypoglycemia, hypoxia and seizures, which are also frequent complications of acute liver failure. Therefore, these parameters must also be monitored. In contrast to acute liver failure in which cerebral dysfunction progresses rapidly, cognitive decline may be clinically undetectable for a long time in cirrhotic patients, until clinically overt symptoms such as psychomotor slowing, disorientation, confusion, extrapyramidal and cerebellar symptoms or a decrease in consciousness occur. Clinically, overt HE is preceded by minimal alterations of cerebral function that can only be detected by neuropsychological or neurophysiological measures, but which nevertheless interfere with the patient's daily living. Rapidly progressing spastic paraparesis (hepatic myelopathy) is a rare complication of cirrhosis. In contrast to HE, it does not respond to blood ammonia lowering therapies but must be considered as an indication for urgent liver transplantation. Cognitive dysfunction has recently been detected in hepatitis C virus (HCV)-infected patients with normal liver function. The patients presented with severe fatigue, cognitive dysfunction and mood disorders. Alterations in brain metabolites, as detected by magnetic resonance spectroscopy, indicated central nervous system alteration in these patients. In contrast to patients with HE, HCV-infected patients did not show motor symptoms or deficits in visual perception, but considerable deficits in attention and concentration ability.

Brain imaging techniques have provided substantial insight into the pathophysiology of hepatic encephalopathy (HE). Magnetic resonance imaging gave hint to the fact that there is an increased deposition of manganese especially in the basal ganglia. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) showed that the preference of the basal ganglia might be due to differences in regional cerebral blood flow and an additional redistribution of blood flow from the cortex to subcortical regions in cirrhotics. PET studies using ammonia as tracer showed that the cerebral metabolism of ammonia and the permeability of the blood brain barrier for ammonia is increased in cirrhotic patients compared to healthy controls. The regional ammonia supply is in accordance with the regional blood flow. In accordance with these findings fluorodesoxyglucose-PET-studies of the brain in cirrhotics showed characteristic alterations of glucose utilisation in the patients with a relative decrease of the glucose utilisation of the cingulate gyrus, the frontomedial, frontolateral, and parieto-occipital cortex, while the glucose utilisation of the basal ganglia, the hippocampus, and the cerebellum was relatively increased. These findings fit well with the clinical characteristics of early stages of HE such as deficits in attention, visuo-spatial orientation, visuo-constructive abilities, motor speed, and accuracy.

Objective: In this study, perfusion CT and diffusion-weighted magnetic resonance imaging (DWI) were compared as means of assessing the ischemic brain in hyperacute stroke., Methods: Twenty patients with ischemic stroke underwent perfusion computed tomography (CT) and magnetic resonance imaging (MRI) studies <3 hours after stroke onset. Cerebral blood flow thresholds were used to delineate the ischemic lesion, penumbra, and infarct. Correlations between the volume of the hypoperfused areas, the abnormality volume in admission DWI and follow-up CT/MRI studies, and the clinical National Institutes of Health Stroke Scale (NIHSS) scores were performed., Results: The volume of the ischemic (core and penumbra) lesion on admission perfusion CT was correlated with the volume of admission DWI abnormalities (r=0.89, P=0.001). The infarcted core tissue volume (on admission CT) correlated more strongly (r=0.77, P=0.0001) than the admission DWI abnormality volume (r=0.69, P=0.002) with the follow-up infarct volume on fluid-attenuated inversion recovery images. A correlation was demonstrated between infarct volume in perfusion CT and follow-up DWI abnormality volume (r=0.89, r=0.77, P=0.002). Significant correlations were found between ischemic and infarct region volumes in perfusion CT and NIHSS admission and follow-up scores (P < or = 0.01)., Conclusions: Both imaging modalities provide a sufficient assessment of the hyperacute brain infarct, with significant correlation between them and the clinical condition at admission. Perfusion CT allows differentiation of the penumbra and infarct core region with significant predictive value of follow-up infarct volume and clinical outcome.

Background/aims: Up to 50% of patients infected with the hepatitis C virus (HCV) complain of chronic fatigue and difficulties in concentration and memory. The aim of the present study was to seek evidence for the presence of central nervous system involvement in HCV infected patients with only mild liver disease., Methods: Thirty HCV infected patients with normal liver function, 15 of whom were identified as having mild and 15 moderate to severe fatigue using the fatigue impact scale, underwent neurological and neuropsychological examination, electroencephalography (EEG) and cerebral proton magnetic resonance imaging (MRI) and spectroscopy (MRS). Fifteen healthy volunteers, matched for age and educational attainment, served as controls., Results: In comparison to the healthy controls the patients with HCV infection showed evidence of cognitive impairment, primarily attention and higher executive functions, higher levels of anxiety and depression and impairment of quality of life. In addition they showed a significant decrease of the N-acetyl-aspartate/creatine ratio in the cerebral cortex on 1H MRS while the EEG was slowed in 25%. In general the deficits were more marked in the patients with moderate rather than mild fatigue., Conclusions: The data provide evidence of central nervous system involvement in patients with HCV infection.

Clinical and histopathological findings hint at regional differences in the brain's sensitivity to metabolic changes in cirrhosis. The aim of the present study was to examine regional differences in cerebral ammonia metabolism in patients with cirrhosis and grade 0-to-I hepatic encephalopathy (HE). (13)N-ammonia, (15)O-water positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed. Quantitative values of cerebral blood flow (CBF) and the initial cerebral ammonia uptake rate (K1) were derived for several regions of interest from images of the desired parameters after interactive coregistration with the patients' MRI-studies. CBF (mL/mL/min), K1 (mL/mL/min), and the ammonia extraction fraction (K1/CBF) showed marked regional variance with the highest levels in the thalamus, the lenticular nucleus, and the cerebellum. In conclusion, the regional differences in cerebral ammonia uptake correspond to the distribution of histopathological changes in the brain of patients with cirrhosis as well as clinical features of HE, characterized by signs of basal ganglia and cerebellar dysfunction with corresponding signs of functional impairment, especially of the frontal cortex and cingulate gyrus.