Absence of an infarct on MRI is not uncommon after clinical diagnosis of ischemic stroke.

INTRODUCTION: An infarct on brain MRI is often seen as gold standard when diagnosing ischemic stroke. Although MRI has high sensitivity in detecting a lesion shortly after ischemic stroke, this rapidly declines when time progresses. We assessed the occurrence of a negative MRI 4-6 weeks after a discharge diagnosis of ischemic stroke, and compared the clinical characteristics of patients with a positive or negative MRI. PATIENTS AND METHODS: The first 125 patients from a prospective longitudinal study of cognitive recovery after ischemic stroke were included in this study. Clinical characteristics were collected during admission. Per protocol, 4-6 weeks after stroke a brain MRI was performed. We operationalized different levels of certainty of the clinical diagnosis of ischemic stroke of a panel of 3 expert vascular neurologists. RESULTS: Thirty patients (24%) were MRI negative. Patients that were MRI negative had lower stroke severity at admission, shorter duration of hospital-stay, and better functional status at discharge. The panel judged that 18/30 (60%) MRI negative patients and 27/30 (90%) MRI positive patients had a likely diagnosis of ischemic stroke. Compared to MRI negative patients with a less likely diagnosis, those with a likely diagnosis had higher admission stroke severity and more often received an acute intervention. DISCUSSION AND CONCLUSION: Absence of an infarct on MRI is not uncommon 4-6 weeks after a clinical diagnosis of ischemic stroke. The relatively high proportion of MRI negative strokes with a likely clinical diagnosis of ischemic stroke indicates that neurologists should be cautious ruling out the diagnosis based on MRI beyond the acute stroke stage.

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND AND PURPOSE: Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. METHODS: PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. RESULTS: Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). CONCLUSIONS: Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR2365.

Interaction of attention and acoustic factors in dichotic listening for fused words.

Two dichotic listening experiments examined the degree to which the right-ear advantage (REA) for linguistic stimuli is altered by a "top-down" variable (i.e., directed attention) in conjunction with selected "bottom-up" (acoustic) variables. Halwes fused dichotic words were administered to 99 right-handed adults with instructions to attend to the left or right ear, or to divide attention equally. Stimuli in Experiment 1 were presented without noise or mixed with noise that was high-pass or low-pass filtered, or unfiltered. The stimuli themselves in Experiment 2 were high-pass or low-pass filtered, or unfiltered. The initial consonants of each dichotic pair were categorized according to voice onset time (VOT) and place of articulation (PoA). White noise extinguished both the REA and selective attention, and filtered noise nullified selective attention without extinguishing the REA. Frequency filtering of the words themselves did not alter performance. VOT effects were inconsistent across experiments but PoA analyses indicated that paired velar consonants (/k/ and /g/) yield a left-ear advantage and paradoxical selective-attention results. The findings show that ear asymmetry and the effectiveness of directed attention can be altered by bottom-up variables.

A method to analyze low signal-to-noise ratio functional magnetic resonance imaging data.

The current practice of using a single, representative hemodynamic response function (canonical HRF) to model functional magnetic resonance imaging (fMRI) data is questionable given the trial-to-trial variability of the brain's responses. In addition, the changes in blood-oxygenation level due to sensory stimulation may be small, especially when auditory stimuli are used. Here we introduce a correlation-based single trial analysis method for fMRI data analysis to deal with the low signal-to-noise (SNR) ratio and variability of the HRF in response to repeated, identical auditory stimuli. The correlation technique identifies the "active" trials, i.e., those showing a robust hemodynamic response among all single trials. Using data collected from 14 healthy subjects, it was found that the correlation method can find significant differences between brain areas and brain states in actual fMRI data. Also, the correlation-based method confirmed that the superior temporal gyrus (STG), inferior frontal gyrus (IFG), dorsolateral prefrontal cortex (DLPFC) and thalamus (THA) are involved in auditory information processing in general, and the involvement of the bilateral STG, right THA and left DLPFC in sensory gating. In contrast, conventional analysis failed to find any regions involved in sensory gating. The findings suggest that our single trial analysis method can increase the sensitivity of fMRI data analysis.

Quality of Life after Young Ischemic Stroke of Mild Severity Is Mainly Influenced by Psychological Factors.

BACKGROUND: Long-term prognosis in terms of quality of life (QoL) in young stroke patients is of importance because they usually have a long life expectancy and extensive daily life demands. We aimed at determining which medical and psychological factors influence the QoL in young stroke patients (<50 years), after long-term follow-up. METHODS: Young ischemic stroke patients admitted to the St. Elisabeth Hospital and the TweeSteden Hospital, Tilburg, the Netherlands, between 2000 and 2010 were included. One hundred seventy patients and 61 controls filled out the following questionnaires: (1) the Hospital Anxiety and Depression Scale, (2) the Fatigue Assessment Scale, and (3) the shortened World Health Organization Quality of Life scale. Using linear multiple regression analysis, we assessed the factors influencing QoL. RESULTS: QoL did not differ significantly between patients (median modified Rankin Scale score at follow-up, 0) and controls after a mean follow-up of 4.5 (standard deviation, 2.8) years. The presence of excessive fatigue was associated with lower scores on all domains of the QoL (P ≤ .003), but not for general health domain (P = .010). Similarly, depression was associated with worse QoL on the physical (P = .004) and psychological (P = .001) domains and anxiety with lower scores on the psychological (P < .001) QoL domain. No relationship was found between stroke-specific factors and QoL. CONCLUSIONS: Fatigue and to a lesser extent depression and anxiety affect the QoL in young adults after ischemic stroke of mild severity. Therefore, young stroke patients should be informed about, screened, and, if possible, treated for fatigue, depression, and anxiety.

Long-term cognitive outcome of ischaemic stroke in young adults.

BACKGROUND: Long-term prognosis in terms of cognition in young stroke patients is very important because these patients usually still have a long life expectancy and rather extensive daily life demands. However, little is known on cognitive deficits in these patients. We aimed to evaluate cognitive function in young stroke patients (<50 years) after long-term follow-up. METHODS: Young adults with first-ever ischaemic stroke admitted to St. Elisabeth Hospital or the TweeSteden Hospital, Tilburg, the Netherlands, between January 2000 and December 2010 were included. Patients with severe aphasia or pre-existent cognitive impairment were excluded. Cognitive functioning was assessed using a neuropsychological examination focussing on the following cognitive domains: visual perception, visual and verbal memory, mental speed, and executive functioning. Raw scores were compared to the scores of 61 controls using a multivariate analysis of variance with adjustment for education level. RESULTS: The 96 participants (median age at index event 43.0 years; 45.8% male) performed worse than controls on the Stroop Color-Word Test Part 1 (p < 0.001) and on the Symbol-Digit Substitution Task (p < 0.001), both assessing mental speed. Patients had significantly lower scores on the learning slope of the Word Pair test (p = 0.002) assessing verbal memory. Patients performed better on the Rey-Osterrieth Complex Figure than controls (p < 0.001). CONCLUSIONS: In young patients with ischaemic stroke, mental slowness is present even up to 10 years after stroke. When counselling these patients, doctors should actively try to assess the presence of cognitive deficits, also after a long period of follow-up.

A computational model for generation of the P300 evoked potential component.

The P300 is an endogenously evoked potential with amplitude and latency depending on the amount of information carried by the stimulus rather than its physical characteristics. It has been suggested that P300 is a manifestation of the context updating mechanism in the human working memory. We present a neural network-based model that mimics the learning and forgetting mechanisms of external stimuli in the human working memory that are believed to be responsible for P300 generation. A modified version of the Hebbian learning rule has been devised to govern the weight dynamics of the network. The model was validated by comparing the characteristics of simulated P300 with actual experimental findings such as the relationship between P300 amplitude and stimulus probability, and task relevance. The results show that the proposed P300 model mimics many aspects of the nervous system responsible for P300 generation.

Impact of visual art on patient behavior in the emergency department waiting room.

BACKGROUND: Wait times have been reported to be one of the most important concerns for people visiting emergency departments (EDs). Affective states significantly impact perception of wait time. There is substantial evidence that art depicting nature reduces stress levels and anxiety, thus potentially impacting the waiting experience. STUDY OBJECTIVES: To analyze the effect of visual art depicting nature (still and video) on patients' and visitors' behavior in the ED. METHODS: A pre-post research design was implemented using systematic behavioral observation of patients and visitors in the ED waiting rooms of two hospitals over a period of 4 months. Thirty hours of data were collected before and after new still and video art was installed at each site. RESULTS: Significant reduction in restlessness, noise level, and people staring at other people in the room was found at both sites. A significant decrease in the number of queries made at the front desk and a significant increase in social interaction were found at one of the sites. CONCLUSIONS: Visual art has positive effects on the ED waiting experience.

Auditory evoked potentials of adults who do or do not show a significant right ear advantage in dichotic listening.

The Halwes Fused Dichotic Words Test was used to divide a sample of university students into a group having a statistically significant right ear advantage (REA) and a group having either a significant left ear advantage or a non-significant ear asymmetry (NREA). Of these participants, 30 (14 REA, 16 NREA) had electrical potentials measured from temporal, central, and frontal sites as series of brief tones were presented monaurally. No behavioural response was required. Group differences were found in the latency but not the amplitude of the averaged event-related responses. The REA group showed faster conduction to the right hemisphere than to the left hemisphere. In both groups the amplitude of left hemisphere responses was greater for right ear stimulation than for left ear stimulation. The results for amplitude indicate that the crossed auditory pathway is a superior conductor of information to the left hemisphere but not to the right hemisphere. Group differences, however, are related only to the speed with which information reaches the right hemisphere.

[A male patient with acute, reversible blindness]. / Een man met acute, reversibele blindheid.

BACKGROUND: Intra-arterial thrombectomy (IAT) in occlusions of the posterior cerebral artery (PCA) is uncommon and not a proven therapeutic solution, but can be performed in individual cases. CASE DESCRIPTION: An 80 year old man visited the emergency room after experiencing acute blindness. This was caused by a new hemianopia for the left visual field due to an occlusion of the right PCA, on top of a pre-existing hemianopia for the right visual field. Auxiliary testing showed an old ischemic stroke of the right occipital lobe, and a new occlusion of the right PCA. After deliberation with the patient, it was decided to perform IAT, because of the debilitating effect of the current neurological disabilities. IAT was succesfull and the patient completely recovered to the pre-existing level of functioning. CONCLUSION: Although there is no indisputable evidence to suggest that IAT in occlusions of the PCA is safe and effective, this case illustrates that IAT can be considered on an individual basis. Based on individual patient characteristics and shared decision making, IAT can be performed after carefull consideration of the risks and benefits.

On the relationship between human sensorimotor adaptability and event-related potentials.

It was explored if the speed with which an individual learns to deal with new environments and challenges can be predicted on the basis of his/her brain's response to irrelevant (repeating) and novel auditory stimuli. In this study, 26 subjects threw 30 light-weight balls at a target with and without vision-distorting goggles. The horizontal displacement from a bull's-eye target was measured and the rate and degree of adaptation were computed. The adaptation parameters were correlated with evoked and event-related potential (EP/ERP) measures of the subject's ability to suppress irrelevant information and respond to novel stimuli. Only a weak (or a trend to) correlation was found between the behavioral adaptation and some of the EP/ERP measures. The correlations were limited to EP parameters in the 100 to 200 ms post-stimulus range reflecting the ability to suppress irrelevant information. Thus we conclude that the speed with which an individual adapts to a new environment is at best weakly correlated with brain activity associated with stimulus memory and classification.

Evoked potential variability.

An unsupervised correlation-based clustering method was developed to assess the trial-to-trial variability of auditory evoked potentials (AEPs). The method first decomposes single trials into three frequency bands, each containing activity primarily associated with one of the three major AEP components, i.e., P50, N100 and P200. Next, single-trial evoked potentials with similar post-stimulus characteristics are clustered and selectively averaged to determine the presence or absence of an AEP component. The method was evaluated on actual AEP and spontaneous EEG data collected from 25 healthy participants using a paradigm in which pairs of identical tones were presented, with the first stimulus (S1) presented 0.5s before the second stimulus (S2). Homogeneous, well-separated clusters were obtained and substantial AEP variability was found. Also, there was a trend for S2 to produce fewer 'complete' (and significantly smaller) responses than S1. Tests conducted on spontaneous EEG produced similar clusters as obtained from EP data, but significantly fewer stimuli produced responses containing all three EP components than seen in AEP data. These findings suggest that the clustering method presented here performs adequately to assess trial-to-trial EP variability. Also, the results suggest that the sensory gating observed in normal controls may be caused by the fact that the second stimulus generates fewer 'responsive' trials than the first stimulus, thus resulting in smaller ensemble averages.

A pilot study of rivastigmine in the treatment of delirium after stroke: a safe alternative.

BACKGROUND: Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine. METHODS: This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge. RESULTS: No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2-17). CONCLUSION: Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke. TRIAL REGISTRATION: Nederlands Trial Register NTR1395.

Oscillatory neural network for pattern recognition: trajectory based classification and supervised learning.

Computer algorithms that match human performance in recognizing written text or spoken conversation remain elusive. The reasons why the human brain far exceeds any existing recognition scheme to date in the ability to generalize and to extract invariant characteristics relevant to category matching are not clear. However, it has been postulated that the dynamic distribution of brain activity (spatiotemporal activation patterns) is the mechanism by which stimuli are encoded and matched to categories. This research focuses on supervised learning using a trajectory based distance metric for category discrimination in an oscillatory neural network model. Classification is accomplished using a trajectory based distance metric. Since the distance metric is differentiable, a supervised learning algorithm based on gradient descent is demonstrated. Classification of spatiotemporal frequency transitions and their relation to a priori assessed categories is shown along with the improved classification results after supervised training. The results indicate that this spatiotemporal representation of stimuli and the associated distance metric is useful for simple pattern recognition tasks and that supervised learning improves classification results.

The Location and Effects of Visual Hemisphere-Specific Stimulation on Reading Fluency in Children With the Characteristics of Dyslexia.

Fluency is used as an indicator of reading proficiency. Many students with reading disabilities are unable to benefit from typical interventions. This study is designed to replicate Lorusso, Facoetti, Paganoni, Pezzani, and Molteni's (2006) work using FlashWord, a computer program that tachistoscopically presents words in the right or left visual hemi-field in English and locates through fMRI imaging the processing areas involved in fluency development. Our participants were 15 students who were ages 8 to 19 years and had reading disabilities randomly assigned to Intervention ( n = 9) and Delayed Intervention ( n = 6) groups. Functional imaging studies focused on analyzing activations in the left hemisphere (LH) superior temporal gyrus, the inferior frontal gyrus, and the LH inferior occipito-temporal/fusiform area (visual-word form area [VWFA]). Analysis of intervention data showed that 6 of the 9 Intervention group participants (67%) achieved levels of automatic processing and increased their reading rate by an average of 20 words per minute after participating in the FlashWord intervention. Analyses of fMRI group activation maps and mean activation levels in regions of interest document processing changes in VWFA activations that could be related to the increase in reading speed and confirm these locations as essential to developing fluency.

Vital working hour schemes: The dynamic balance between various interests.

"Balancing Interests", the theme of the 17th International Symposium on Shift Work and Working Time held in Hoofddorp, The Netherlands (September 2005), refers to the ambition to reach an optimal balance between the various aspects of shift work. Economic, ergonomic, physical, and psychosocial factors all interact in determining the impact of shift work at the individual, organizational, and societal level. It is the challenge of this multidisciplinary field of research to model all relevant factors in such a way that it will allow us to optimize the dynamic trade-off between the yield and the risk of shift work. The organizers of the 17th International Symposium and the co-editors of these proceedings are convinced that the high quality of the contributions will bring us closer to this ultimate goal.

[A man with vision problems after coronary angiography]. / Een man met visusklachten na coronairangiografie.

A 71-year-old man underwent a coronary angiography (CAG). Afterwards he experienced vision loss. Neurologic examination revealed bilateral cortical blindness. A cerebral CT-scan showed occipital hyperdensity, due to contrast accumulation and oedema. There was complete recovery of vision within 2 days. Transient cortical blindness after CAG is a rare complication of iodinated contrast agents.

Morphological and latency abnormalities of the mid-latency auditory evoked responses in schizophrenia: a preliminary report.

INTRODUCTION: Evoked potential (EP) amplitude and latency abnormalities have been extensively examined in schizophrenia. Morphological abnormalities of the mid-latency auditory evoked responses (MLAERs; P50, N100, P200), on the other hand, received very little attention. METHODS: Based on a priori defined set of morphological criteria, the morphology and latency of the MLAERs were blindly compared between stable outpatients with schizophrenia (N=27) and age- and gender-matched healthy control subjects (N=22). The morphology of the MLAERs was considered abnormal if one or more of the components fell outside the expected latency range, if one or more of the components were missing, or if a later occurring component was smaller in amplitude than an earlier occurring one. RESULTS: Of the 27 schizophrenia subjects, 20 had waveforms that were deemed atypical, while only 8 from the control group were classified as atypical (chi(2)=5.52, p<0.02). The latencies of the P50 and N100 components, identified based on morphology, were significantly prolonged in schizophrenia patients. CONCLUSIONS: These preliminary data suggest that morphological abnormalities of the MLAERs in schizophrenia patients are significant and should be taken into consideration when examining the MLAERs of this patient population.

Contribution of different EEG frequencies to auditory evoked potential abnormalities in schizophrenia.

OBJECTIVE: We have shown previously [Clin Neurophysiol 2003;114:79] that phase reorganization of the ongoing electroencephalogram (EEG) plays an important role in the generation of auditory evoked potential (EP) components with a latency between 50 and 200 ms. In the present study, we investigate whether schizophrenia patients suffer from phase synchronization deficits as compared to normal subjects. METHODS: The auditory EPs from 20 normal subjects and 19 schizophrenia patients were analyzed. EPs were obtained using a double stimulus paradigm, in which two identical tone bursts (S1 and S2) were delivered with an average inter-stimulus interval of 500 ms and an inter-pair interval of 8 s. The Piecewise Prony Method (PPM) was used to decompose single trial auditory evoked potentials into different frequency bands. Pre- and post-stimulus phase histograms were compared for each frequency band to determine the degree of phase synchronization produced by auditory stimulation in the two populations. RESULTS: The S1 stimulus produced significantly less (P < 0.05) phase synchronization in schizophrenia patients than in normal subjects in the 2-12 Hz frequency range. Far fewer and smaller inter-population phase synchronization differences were seen for the S2 stimulus. Both populations showed more phase synchronization for S1 than S2. A significant correlation (P < 0.01) between N100 amplitude and phase synchronization 100 ms post S1 was observed for the normal population but not for the schizophrenia group. The correlation between P200 amplitude and phase synchronization 200 ms post S1 was significant for the normal group (P < 0.01) and the schizophrenia group (P < 0.03). CONCLUSIONS: Schizophrenia patients have a phase synchronization deficiency, as compared to a normal control group, especially for the first stimulus, in the 2-12 Hz frequency range. This deficiency explains the lower EP amplitudes and may be a significant factor contributing to reduced sensory gating reported in schizophrenic subjects. SIGNIFICANCE: The research presented here contributes to the understanding of the mechanism underlying sensory gating in health and gating deficiencies in schizophrenia.

Phase synchronization of the ongoing EEG and auditory EP generation.

OBJECTIVE: We investigated the role of phase synchronization of the spontaneous electroencephalogram (EEG) in auditory evoked potential (EP) generation in a sample of healthy individuals. METHODS: Auditory responses were obtained from 20 healthy subjects following a double stimulus paradigm, using two identical tone bursts (S1 and S2) separated by 0.5s. Single-trial auditory evoked potentials were decomposed into sinusoidal, exponentially decaying/increasing components using the piecewise Prony method (PPM). Pre- and post-stimulus phase histograms were compared to determine the degree of phase synchronization produced by auditory stimulation. RESULTS: Analysis of single responses revealed that the S1 stimuli produced phase synchronization in the 2-8Hz frequency range, with little or no concomitant amplitude increase. A significantly reduced phase effect was seen in response to S2 stimuli. CONCLUSIONS: Stimulus-induced phase synchronization of the ongoing EEG is a major mechanism for the generation of auditory EP components with a latency in the 50-250ms range. SIGNIFICANCE: The fact that the EP components accessed here are generated through phase synchronization implies that the ensemble-averaged EP will not resemble the single trial response, and it would certainly be misleading to consider the single trial response as an amplitude-scaled version of the ensemble average.