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Biomedical subjects

A Villringer

Publications and source records attributed to A Villringer.

At least 19 recordsLinked to original sources

[Two simple questions to diagnose post-stroke depression].

BACKGROUND AND PURPOSE: Many patients develop a depression after having suffered a stroke. Such a Post-Stroke Depression (PSD) impairs rehabilitation and quality of life. PSD is underdiagnosed in spite of available treatment. Several questionnaires have been created to diagnose a PSD. But questionnaires have been considered cumbersome and time-consuming. The aim of this study was to find out whether two simple, standardised questions will identify those stroke patients, who have developed a PSD. METHODS: The two case-finding questions and the Beck Depression Inventory (BDI) were sent to patients of the Berlin Acute Stroke Study (BASS) four years after their stroke. Incomplete questionnaires were complemented via mail or telephone. Severity of depression was assessed by means of BDI. RESULTS: Out of 211 patients, 199 responded to the questionnaire (94 %). 193 questionnaires were complete (97 %). Forty-two patients affirmed both case-finding questions (22 %). Compared to patients, who did not affirm both questions, these patients had a higher BDI score (19 +/- 8 vs. 7 +/- 5; p < 0.001). The sensitivity and specificity of the two questions were 89 % and 90 %, respectively. The positive and negative predictive value were 60 % and 98 % respectively. The number of confirmed questions (0, 1, 2) correlated well with the BDI score (r (2) = 0.67, p < 0.001). CONCLUSIONS: Two standardized questions can identify patients with PSD for further diagnostic evaluation and therapy. Diagnosis of PSD might be facilitated by using them as screening instrument.

Aged↗

Non-invasive detection of fluorescence from exogenous chromophores in the adult human brain.

This is the first report on results proving that fluorescence of exogenous dyes inside the human brain can be excited and detected non-invasively at the surface of the adult head. Boli of indocyanine green (ICG) were intravenously applied to healthy volunteers, and the passage of the contrast agent in the brain was monitored by detecting the corresponding fluorescence signal following pulsed laser excitation at 780 nm. Our hypothesis that the observed fluorescence signal contains a considerable cortical fraction was corroborated by performing measurements with picosecond temporal resolution and analyzing distributions of times of arrival of photons, hence taking advantage of the well-known depth selectivity of that method. Our experimental findings are explained by Monte Carlo simulations modeling the head as a layered medium and taking into account realistic bolus kinetics within the extra- and intracerebral compartment. Although a particular non-specific dye (ICG) was used, the results clearly demonstrate that fluorescence-mediated imaging of the adult human brain is generally feasible. In particular, we will discuss how these results serve as proof of concept for non-invasive fluorescence brain imaging and may thus open the door towards optical molecular imaging of the human brain.

Adult↗

Emergency department delays in acute stroke - analysis of time between ED arrival and imaging.

We determined the factors leading to emergency department (ED) delays in patients with acute stroke. Data were collected prospectively in four Berlin inner-city hospitals by ED documentation, medical records, imaging files and patient interviews. An extended Cox proportional hazards model was fitted to the data. Analyses were performed in 558 patients with confirmed diagnosis of stroke. Median time from admission at ED to beginning of computed tomography/magnetic resonance imaging (CT/MRI) was 108 min. In a subgroup of patients potentially eligible for thrombolysis with a pre-hospital delay <120 min and a National Institutes of Health Stroke Scale (NIHSS) >4 (n = 74), the median interval to imaging was 68 min. Multivariable analysis revealed that a more severe initial NIHSS, a pre-hospital delay <3 h, admission at two specific hospitals, admission at weekends, and private health insurance were significantly associated with reduced delays. In stroke patients, the time interval between ED admission and imaging depends both on factors that emerge from clinical needs and on factors independent of clinical necessities. Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for both improvement of in-hospital management and of medical and non-medical factors influencing pre-hospital delays.

Aged↗

The use of radiolabelled human serum albumin and SPECT/MRI co-registration to study inflammation in the cavernous sinus of cluster headache patients.

A sterile inflammation in the cavernous sinus was hypothesized to underlie cluster headache (CH). Neurogenic inflammation is accompanied by the extravasation of plasma proteins in the surrounding tissue. We tested the hypothesis of an inflammatory process in the cavernous sinus in CH patients using 99mTc-human serum albumin (HSA) and single photon emission computed tomography (SPECT). Six patients with episodic CH were enrolled. After baseline imaging, CH attacks were induced by IV injection of nitroglycerin. The patients remained untreated for 20 min. A second SPECT was performed after successful treatment. Region of interest (ROI) analysis was performed on the basis of coregistered MRI/SPECT data. There was no statistical difference between the 99mTc-HSA uptake in the ipsilateral cavernous sinus before and after induction of an acute CH attack. There was no evidence for 99mTc-HSA extravasation in the cavernous sinus during the active episode as compared with the remission phase. Our results do not support the hypothesis of an inflammation in the cavernous sinus.

Adult↗

Reward-based decision-making and aging.

Healthy aging is associated with a number of neuroanatomical and neurobiological alterations that result in various cognitive changes. Both, the dopaminergic as well as the serotonergic system are subject to change during aging. Receptor loss and severe structural changes in PFC and striatum have been reported. Aging is associated with a progressive decline in several cognitive functions, such as episodic memory, working memory, and processing speed. Furthermore, it is associated with deficits in tasks requiring adaptation to external feedback of right or wrong, or task-switching. Here, we develop the hypothesis that this loss of behavioral flexibility is caused by structural and functional alterations of the reward system leading to impairments in reward processing, learning stimulus reinforcement associations, and reward-based decision-making. We review (a) data on neural correlates and substrates of reward processing in young healthy animals and humans, (b) evidence for age related functional and structural alterations of the reward system, and (c) behavioral and neuroimaging data of age effects on reward-based decision-making processes. Implications for neuroeconomics and neurodegenerative diseases are discussed.

Aging↗

[Symptoms, risk factors, and etiology of transient ischemic attack and stroke].

BACKGROUND: It is unclear whether clinical signs and symptoms differ in the presentation of transient ischemic attack (TIA) and stroke, apart from temporal dynamics. METHODS: Signs and symptoms of patients diagnosed with TIA or stroke were prospectively collected and compared by means of an age-adjusted logistic regression analysis. Risk factors, prehospital medication, and diagnostic workup were obtained from the charts. RESULTS: Four hundred five patients diagnosed with stroke (68+/-12 years old, 45% female) and 143 diagnosed with TIA (64+/-14 years old, 48% female) were included. Signs and symptoms of patients with TIA were less often "classic" such as paresis (48% vs 71%, P<0.001) or sensory loss (38% vs 48%, P=0.03). The etiology of TIA was more often classified as "undetermined" (57% vs 46%, P<0.05). CONCLUSIONS: Transient ischemic attack needs special attention and intensive diagnostic workup, because it bears a considerable risk of death and disability but presents less often with classic signs and symptoms and its etiology often remains undetermined.

Aged↗

Ultrasound perfusion imaging of cysts in the midbrain.

AIM: Cerebral ultrasound perfusion examinations have been focused on the diencephalic plane. We describe perfusion abnormalities in the mesencephalon. METHOD: Phase-Inversion-Harmonic-Imaging (PIHI, Siemens Sonoline Elegra) was performed in a patient with ponto-mesencephalic cysts, that was defined by MRI. The signal increase (bolus kinetics, SonoVue) was quantified for peak-signal-increase (PSI) and time-to-peak (TTP). RESULTS: PSI and TTP could be quantified for the ipsi- and contralateral posterior cerebral arteries, the ipsilateral middle cerebral artery, the mesencephalon and the ipsilateral temporal lobe. The contrast agent influx was diminished or extinct in the area of the cysts. PSI and TTP delineated the area of the cystic structure well. CONCLUSION: PIHI in the mesencephalic plane is feasible and allows identification of pathological structures within the mesencephalon.

Brain Diseases↗

Medical resource use and costs of health care after acute stroke in Germany.

The purpose of this study was to determine the 12 months medical resource use following admission to hospital with acute stroke and to calculate costs from a societal perspective. Data of consecutive patients with confirmed stroke were analysed. Acute hospital data were taken from medical records, socio-demographic variables from patients' interviews. A follow-up questionnaire about resource utilization was completed by patients or proxies 12 months after acute hospital admission. Costs were calculated by multiplying medical resource units used with cost factors per unit. Mean age of a total of 383 patients was 65 years and 41% were female. The median length of the initial stay in the acute hospital was 12 days at an average cost of 4650 per patient (49% of direct costs). Rehabilitation (16%), readmission (11%), medication (9%), and nursing costs (6%) were other contributors to the direct costs which amounted to a total of 9452 +/- 7599 per patient during 12 months. Indirect cost amounted to a total of 2014 +/- 5312. Patients' age, severity and type of stroke influenced the total stroke-associated costs. The large economic burden of stroke indicates the need for assessing and improving efficient health care for affected patients.

Aged↗

Bed-side assessment of cerebral perfusion in stroke patients based on optical monitoring of a dye bolus by time-resolved diffuse reflectance.

We present a minimally invasive optical method, that is, multi-channel time-domain diffuse near-infrared reflectometry of the head to assess cerebral blood perfusion that is applicable at the bed-side and repetitively at short intervals. Following intravenous injection of an ICG bolus, its transit through intra- and extracerebral tissue is monitored based on changes in moments of distributions of times of flight of photons, recorded with a 4-channel instrument simultaneously on both hemispheres. In healthy volunteers, we found that variance of distributions of times of flight of photons is well suited to assess latency and initial slope of the increase in absorption of intracerebral tissue due to the bolus. We successfully applied our method in two patients demonstrating a reversible cerebral perfusion deficit in an ischemic stroke patient who was treated by thrombolysis and in another patient with a permanent impaired unilateral perfusion due to ipsilateral internal carotid artery occlusion. In either case, we observed a difference in bolus transit time between the hemispheres. In the stroke patient, this difference resolved when re-evaluated 1 day after thrombolysis. The study demonstrates the necessity of a technique with sub-nanosecond time resolution to allow for depth discrimination if clinical perfusion monitoring of cerebrovascular diseases is addressed by optical methods.

Adult↗

Effect of aging on stimulus-reward association learning.

The flexible learning of stimulus-reward associations when required by situational context is essential for everyday behavior. Older adults experience a progressive decline in several cognitive functions and show deficiencies in neuropsychological tasks requiring flexible adaptation to external feedback, which could be related to impairments in reward association learning. To study the effect of aging on stimulus-reward association learning 20 young and 20 older adults performed a probabilistic object reversal task (pORT) along with a battery of tests assessing executive functions and general intellectual abilities. The pORT requires learning and reversing associations between actions and their outcomes. Older participants collected fewer points, needed more trials to reach the learning criterion, and completed less blocks successfully compared to young adults. This difference remained statistically significant after correcting for the age effect of other tests assessing executive functions. This suggests that there is an age-related difference in reward association learning as measured using the pORT, which is not closely related to other executive functions with respect to the age effect. In human aging, structural alterations of reward detecting structures and functional changes of the dopaminergic as well as the serotonergic system might contribute to the deficit in reward association learning observed in this study.

Adult↗

Effect of incomplete (spontaneous and postthrombolytic) recanalization after middle cerebral artery occlusion: a magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Early reperfusion is one of the best predictors of good outcome after acute middle cerebral artery (MCA) occlusion. The purpose of this study was to analyze the frequency and relevance of incomplete recanalization for tissue and clinical outcome. METHODS: From a larger acute stroke database (Kompetenznetzwerk Schlaganfall B5), all patients (n=82) with MCA main stem occlusion (excluding carotid T-occlusions) were selected. These patients had received a multiparametric stroke MRI protocol including diffusion- and perfusion-weighted imaging (DWI, PWI) and MR angiography (MRA) within 6 hours after symptom onset, at day 1 and after 1 week. Recanalization status was determined with MRA on day 1 (according to Thrombolysis In Myocardial Infarction flow grades) and used to group patients into those with persistent occlusion (0) or minimal (1), partial (2), or complete (3) recanalization. RESULTS: Incomplete recanalization according to MRI criteria was found in 39 patients (grade 1: n=20; grade 2: n=19), complete recanalization in 10, and persistent occlusion in 33. There was no statistically significant difference in any of the clinical (National Institutes of Health Stroke Scale score) or MRI baseline parameters (DWI lesion, PWI deficit, mismatch volume, mismatch ratio). However, lesion growth was smaller in patients with recanalization (even in patients with only minimal recanalization) and outcome was related to the degree of recanalization (mean modified Rankin score at 90 days: 3.36, 2.70, 1.79, and 1.44 for the groups with no, minimal, partial, and complete recanalization, respectively). Both incomplete and complete recanalization was more frequent in patients receiving thrombolysis. CONCLUSIONS: Incomplete recanalization on day 1 is a frequent MR finding after MCA main stem occlusion, indicating a more favorable clinical course than persistent occlusion. MR indicators of early recanalization could be useful surrogates of efficacy in thrombolytic trials.

Adult↗

[Physiological and technical limitations of functional magnetic resonance imaging (fMRI)--consequences for clinical use].

Functional magnetic resonance imaging (fMRI) is the most common noninvasive technique in functional neuroanatomy. The capabilities and limitations of the method will be discussed based on a short review of the current knowledge about the neurovascular relationship. The focus of this article is on current methodical and technical problems regarding fMRI-based detection and localization of neuronal activity. Main error sources and their influence on the reliability and validity of fMRI-methods are presented. Appropriate solution strategies will be proposed and evaluated. Finally, the clinical relevance of MR-based diagnostic methods are discussed.

Brain Diseases↗

Dipole source localization and fMRI of simultaneously recorded data applied to somatosensory categorization.

In this study, the feasibility of dipole source localization (DSL) and coregistration with functional magnetic resonance imaging (fMRI) activation patterns on the basis of simultaneously acquired data is demonstrated. Brain activity was mapped during the performance of a somatosensory single reaction and a choice reaction task at high spatiotemporal resolution in six healthy subjects. The choice reaction task required a categorization of two different stimulus intensities, whereas for the single reaction task merely the perception of a tactile stimulus had to be confirmed by the subjects. An offline artifact correction algorithm was applied to 32-channel EEG data that were acquired between subsequent MRI scans. Using a multiple dipole approach, five distinct dipole sources were identified within areas of the somatosensory system. Coregistration of fMRI and DSL showed consistent spatial activation patterns with a mean distance of 9.2 +/- 6.8 mm between dipole sources and fMRI activation maxima. However, since the number of fMRI activation sites exceeded the number of cerebral dipole sources, it was not possible to assign a dipole source to each fMRI activation site. Dipole moment time courses were consistent with previously reported results of similar experiments. A comparison of brain activation patterns during the two tasks with both fMRI and DSL indicated an involvement of the contralateral secondary somatosensory cortex in somatosensory categorization.

Adult↗

Heparin treatment in cerebral sinus and venous thrombosis: patients at risk of fatal outcome.

We performed a retrospective analysis of 79 patients with cerebral sinus venous thrombosis, who were treated with a fixed regimen of dose-adjusted intravenous heparin, to determine predictors of a fatal course. The parameters investigated were the state of consciousness and the presence of intracranial haemorrhage (ICH) at the start of heparin treatment, involvement of the internal venous system, mean delay from initial symptom to stupor or coma and from initial symptom to hospital admission, focal neurological deficits, mean intracranial circulation time (ICT) on conventional angiography, and age and sex distribution. Mortality rate was 10% in this series (8/79). There was a strong link between the outcome and the level of vigilance: 53% of the patients with stupor or coma at the start of the heparin therapy died (8/15), whereas all of the 64 patients with no more than mildly impaired vigilance survived (p < 0.00001). Furthermore, mean age and mean ICT were significantly higher in the group of patients who died. There was a statistical trend (p = 0.056) for ICH to be more frequent in cases with fatal outcome, but there was reason to assume that ICH represented an epiphenomenon of a severe course rather than an independent predictor. Other investigated parameters were not linked with a fatal outcome.

Adolescent↗

Cross talk in the Lambert-Beer calculation for near-infrared wavelengths estimated by Monte Carlo simulations.

Using the modified Lambert-Beer law to analyze attenuation changes measured noninvasively during functional activation of the brain might result in an insufficient separation of chromophore changes ("cross talk") due to the wavelength dependence of the partial path length of photons in the activated volume of the head. The partial path length was estimated by performing Monte Carlo simulations on layered head models. When assuming cortical activation (e.g., in the depth of 8-12 mm), we determine negligible cross talk when considering changes in oxygenated and deoxygenated hemoglobin. But additionally taking changes in the redox state of cytochrome-c-oxidase into account, this analysis results in significant artifacts. An analysis developed for changes in mean time of flight--instead of changes in attenuation--reduces the cross talk for the layers of cortical activation. These results were validated for different oxygen saturations, wavelength combinations and scattering coefficients. For the analysis of changes in oxygenated and deoxygenated hemoglobin only, low cross talk was also found when the activated volume was assumed to be a 4-mm-diam sphere.

Absorption↗

Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours.

BACKGROUND AND PURPOSE: The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. METHODS: In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). RESULTS: We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13; P=0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%; P<0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P=0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (< or =3 hours or 3 to 6 hours) (univariate analysis: mRS < or =2, P=0.017; mRS < or =1, P=0.023). Age (P=0.003), thrombolytic therapy at 0 to 6 hours (P=0.01), recanalization (P=0.016), lesion volume on day 7 (P=0.001), and initial National Institutes of Health Stroke Scale score (P=0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P=0.024) but not final infarct volume. CONCLUSIONS: In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.

Acute Disease↗

Representational overlap of adjacent fingers in multiple areas of human primary somatosensory cortex depends on electrical stimulus intensity: an fMRI study.

Functional magnetic resonance imaging (fMRI) was used to examine the influence of non-painful electrical stimulus intensity on the BOLD response in human primary somatosensory cortex (SI). In ten healthy subjects, index and middle finger of the right hand were stimulated separately at two different stimulus intensities. The activated volume of single finger representations as well as the volume of representational overlap of the two activations increased following an increase in stimulus intensity. This effect was seen in two different subdivisions of SI, one in the depth of the central sulcus, presumably corresponding to Brodmann area (BA) 3b, and one on the crown of the postcentral gyrus, presumably corresponding to BA 1/2. Relative overlap (ratio of overlap volume to volume of individual finger representation) was larger in BA 1/2 than in BA 3b. Additionally, in both areas relative overlap increased significantly from low to high stimulus intensity. Relative overlap did not change when different correlation thresholds were employed arguing against an unspecific 'spillover effect'. Analysis of signal intensity time courses indicated that the response difference to high versus low stimulus strength was not present during the initial seconds of stimulation, during which both led to a similar signal intensity increase. Only during the following maintenance level of the response did the response to high stimulus intensity reach a significantly higher plateau level than the one due to low intensity stimulation, an effect which was present in both areas, BA 3b and BA 1/2, respectively.

Adult↗