Frank Donnerstag

ADMA Increases Arterial Stiffness and Decreases Cerebral Blood Flow in Humans

Background and Purpose— Preclinical studies have revealed that the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), increases vascular tone in cerebral blood vessels. Marked elevations of ADMA blood levels were found in patients with diseases characterized by decreased cerebral perfusion, such as ischemic stroke. Arterial stiffness is an independent predictor of stroke and other adverse cardiovascular events. The aim of this study was to investigate the influence of a systemic subpressor dose of ADMA on arterial stiffness and cerebral perfusion in humans. Methods— Using a double-blind, vehicle-controlled study design, we allocated 20 healthy men in random order to infusion of either ADMA (0.10 mg ADMA/kg per min) or vehicle over a period of 40 minutes. Arterial stiffness was assessed noninvasively by pulse wave analysis. All volunteers underwent measurement of cerebral perfusion by dynamic contrast-enhanced perfusion magnetic resonance imaging of the brain. Results— Infusion of ADMA significantly decreased total cerebral perfusion by 15.1±4.5% (P=0.007), whereas blood flow in the vehicle group increased by 7.7±2.8% (P=0.02). ADMA also increased arterial stiffness as assessed by measurement of the augmentation index (−12.6±1.9 to −9.6±1.5, P=0.007). Conclusions— Our results document for the first time that subpressor doses of ADMA increase vascular stiffness and decrease cerebral perfusion in healthy subjects. Thus, ADMA is an important endogenous modulator of cerebral vascular tone and may be involved in the pathogenesis of cerebrovascular disease.

Neuronal correlates of ADHD in adults with evidence for compensation strategies--a functional MRI study with a Go/No-Go paradigm

Objective: Response inhibition impairment is one of the most characteristic symptoms of attention-deficit/hyperactivity disorder (ADHD). Thus functional magnetic resonance imaging (fMRI) during a Go/No-Go task seems to be an ideal tool for examining neuronal correlates of inhibitory control deficits in ADHD. Prior studies have shown frontostriatal abnormalities in children and adolescents. The aim of our study was to investigate whether adults with ADHD would still show abnormal brain activation in prefrontal brain regions during motor response inhibition tasks. Methods: fMRI was used to compare brain activation in 15 untreated adult patients with ADHD and 15 healthy reference volunteers during performance of a Go/No-Go task. Results: In contrast to various other studies with children and adolescents with ADHD, we found no significant difference in the activity of anterior cingulate cortex (ACC) or other frontostriatal structures between ADHD and healthy adults. Significantly enhanced activity was found in the parietal cortex, which is known to play an important role in building up attention. Conclusion: We hypothesize that the enhanced activity is due to the ability of adult ADHD patients to compensate their deficits for a short time, which is demonstrated in our study by equal task performance in both groups.

Comparison of perfusion computed tomography with diffusion-weighted magnetic resonance imaging in hyperacute ischemic stroke.

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 (r2 = 0.77, P = 0.0001) than the admission DWI abnormality volume (r2 = 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, r2 = 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 ≤ 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.

Correlative assessment of cerebral blood flow obtained with perfusion CT and positron emission tomography in symptomatic stenotic carotid disease

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 [15O]H2O 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.

eLearning in education and advanced training in neuroradiology: introduction of a web-based teaching and learning application.

IntroductionNew information technologies offer the possibility of major improvements in the professional education and advanced training of physicians. The web-based, multimedia teaching and learning application Schoolbook has been created and utilized for neuroradiology.MethodsSchoolbook is technically based as a content management system and is realized in a LAMP environment. The content is generated with the help of the developed system and stored in a database. The layout is defined by a PHP application, and the webpages are generated from the system.ResultsSchoolbook is realized as an authoring tool so that it can be integrated into daily practice. This enables the teacher to autonomously process the content into the web-based application which is used for lectures, seminars and self-study. A multimedia case library is the central building block of Schoolbook for neuroradiology, whereby the learner is provided with original diagnostic and therapeutic data from numerous individual cases. The user can put individual emphasis on key learning points as there are various ways to work with the case histories. Besides the case-based way of teaching and learning, a systematically structured way of dealing with the content is available.ConclusioneLearning offers various opportunities for teaching and learning in academic and scientific as well as in economic contexts. Web-based applications such as Schoolbook may be beneficial not only for basic university education but also for the realization of international educational programmes such as the European Master of Medical Science with a major in neuroradiology.

Neurologic manifestations of E coli infection–induced hemolytic-uremic syndrome in adults

Objective: To describe the neurologic and neuroradiologic complications of Shiga toxin producing Escherichia coli infection (STEC)–associated hemolytic-uremic syndrome (HUS) in adults. Methods: All 52 adult patients with STEC O104:H4 infection cared for at Hannover Medical School during the outbreak in Germany through May–July 2011 are considered in this observational study. Forty-three of the 52 patients underwent a standard neurologic diagnostic procedure including clinical examination, Mini-Mental State Examination, and Glasgow Coma Scale Score. Thirty-six patients underwent EEG, and 26 had cerebral MRI, 9 of them repeatedly. Case records of 9 patients who had not been seen by a neurologist were analyzed retrospectively. Results: Forty-eight of the 52 patients had HUS. All but 1 of these showed neurologic symptoms. Focal neurologic signs like double vision, difficulties in finding words, or hyperreflexia were present in 23, additional deficits in orientation, attention, memory, or constructive abilities in 9, and marked impairment of consciousness in 15. MRI showed brainstem, midbrain, thalamus, corpus callosum, and white matter lesions in half of the patients, predominantly in diffusion-weighted images. The extent of MRI lesions did not correlate with clinical symptoms. General slowing but no focal alteration was found in half of the patients examined by EEG. Conclusion: Our findings suggest a toxic-metabolic pathology behind the neurologic impairment instead of multiple infarction due to microthrombosis. Future studies should aim to clarify if early antibiotic therapy or bowel cleansing might help to decrease the rate of neurologic complications in STEC-HUS.

Effect of the arterial input function on the measured perfusion values and infarct volumetric in acute cerebral ischemia evaluated by perfusion computed tomography

Objectives:We sought to evaluate the accuracy of the perfusion computed tomography (PCT) deconvolution-based brain perfusion measurements and the lesions’ (infarct and penumbra) volumetric with regard to arterial input function (AIF) selection in patients with acute stroke. Materials and Methods:Eighteen consecutive patients with symptoms of acute stroke underwent PCT at admission. Follow-up magnetic resonance imaging was obtained in all patients after 3.6 ± 1.7 days (range, 1.5–6 days). PCT maps were generated focusing on the anterior cerebral artery (ACA) and branches of the middle cerebral artery (MCA) ipsilateral and contralateral to the ischemic lesion as AIFs. Infarct, penumbra, and total ischemic lesion were delineated on cerebral blood flow (CBF) maps. CBF, cerebral blood volume (CBV), and mean transit time (MTT) were calculated in the ischemic regions as provided by the 3 different AIFs, the normality test was applied for the obtained parameters, and the values were correlated (Pearsons correlation coefficient). Volumes of the ischemic regions (as obtained by the different AIFs) also were correlated and compared (paired t test) to the follow-up infarct volume. Results:The CBF and CBV values obtained by the different AIFs in the infarct, penumbra, and total ischemic lesion were significantly correlated (r = 0.94–0.96, P ≤ 0.01). Only in the infarct region calculated MTT values were correlated (r = 0.88–0.91, P < 0.05) between the different AIFs groups. High correlation coefficients (r = 0.79–0.91, P < 0.001) were observed between the admission PCT infarct and total ischemic volume and the MRI follow-up infarct volume. ACA as AIF provided the best correlations (r = 0.91, P = 0.0002) with the follow-up measurements. No statistically significant difference was found between the 3 different AIF-estimated admission total ischemic volumes and the follow-up infarct volume. Conclusions:The AIF selection in the ACA as well as in the ipsilateral (to the hypoperfused area) or contralateral branches of the MCA has no statistically significant impact on the calculation of the CBF, CBV values, and the volume estimation of the ischemic region in the acute stroke patients.

Feasibility of central cannabinoid CB1 receptor imaging with [124I]AM281 PET demonstrated in a schizophrenic patient.

We studied central cannabinoid CB1 receptors in a schizophrenic patient using the pyrazole derivative AM281 labelled with the positron-emitting nuclide iodine-124. A dynamic positron emission tomography (PET) acquisition with simultaneous blood sampling was performed up to 1.5 h post-injection. The classical Logan plot analysis was applied to generate a three-dimensional map of distribution volume (DV). The map was spatially normalised into the Montreal Neurological Institute stereotactic space. Using a volume of interest (VOI) template, mean values of DV were extracted from multiple grey matter regions and white matter (as a reference). As a measure of regional receptor availability, ratios of DV in grey matter to DV in white matter minus one (DVR-1) were calculated. The highest receptor binding was observed in the striatum and the pallidum (DVR-1: 0.35-0.37). Binding in basal ganglia regions was lower on the left than the right side. Moderately high binding was seen in the frontal cortex (0.22), the temporal cortex (0.18) and the cerebellum (0.15). In conclusion, 124I-AM281 PET can be used to reveal areas with prominent CB1 receptor binding. Nevertheless, limited image contrast and relatively high radiation exposure (physical half-life of 124I: 4 days) have to be taken into account. Asymmetric receptor binding may possibly reflect pathologic changes in schizophrenia.

Developmental Outcome in Five Children with Hurler Syndrome after Stem Cell Transplantation: A Pilot Study.

Hurler syndrome (mucopolysaccharidosis type 1H; MPS1H) is a lysosomal storage disease caused by a deficiency of α‐L‐iduronidase activity. The natural course of this neurodegenerative disease inevitably leads to premature death within the first 10 years of life. Enzyme replacement therapy is effective in correcting the enzymatic deficiency of organs other than the central nervous system. Hematopoietic stem cell transplantation (SCT) is the only treatment known to prevent psychomotor deterioration. However, the classical transplantation protocols resulted in a high incidence of graft failure and regimen‐related toxicity. Recently, we published a well‐tolerated, fludarabine‐based, radiation‐free conditioning regimen for SCT in patients with Hurler syndrome. Here we report the developmental outcome (assessed by the Denver Developmental Screening Test before and yearly after SCT) of four females and one male with MPS1H (mean age at last follow‐up 71mo, range 42‐87mo) treated in accordance with this strategy. Mean age at SCT was 25 months (range 10‐36mo). All children were engrafted and in ambulatory care. They all showed psychomotor development without neurodegeneration. In all patients, after SCT a regression of intracranial lesions could be seen that paralleled the psychomotor improvements. SCT led to a relative reduction of head circumference in all cases.

Temporal Pattern of Cytotoxic Edema in the Perihematomal Region After Intracerebral Hemorrhage A Serial Magnetic Resonance Imaging Study

Background and Purpose— Knowledge about cytotoxic edema (CE) in intracerebral hemorrhage is still limited. We aimed to analyze its presence, temporal pattern, and prognostic meaning. Methods— Twenty-one patients with primary intracerebral hemorrhage underwent magnetic resonance imaging at days 1, 3, and 7 after symptom onset. CE was identified using diffusion-weighted imaging. Hematoma and perihematomal edema volumes were measured on fluid-attenuated inversion recovery images. National Institutes of Health Stroke Scale score was assessed at admission and with each magnetic resonance imaging. Clinical outcome was assessed by modified Rankin scale at 90 days. Results— CE appeared in half of the patients within the first 24 hours. The apparent diffusion coefficient values decreased until day 3 and were significantly reversed from days 3 through 7 (P<0.01). Patients with CE showed significantly faster perihematomal edema growth from day 0 to 1 (P=0.036) than those without. Larger 3-day perihematomal edema volume (P=0.02) and presence of CE on day 3 (P=0.07) were associated with poor clinical outcome. Conclusions— CE is associated with stroke severity, perihematomal edema volume, and poor outcome. It is considered to indicate ongoing neuronal injury and, thus, might emerge as new treatment target.