Mindfulness in the focus of the neurosciences - The contribution of neuroimaging to the understanding of mindfulness.

Background: Mindfulness affects human levels of experience by facilitating the immediate and impartial perception of phenomena, including sensory stimulation, emotions, and thoughts. Mindfulness is now a focus of neuroimaging, since technical and methodological developments in magnetic resonance imaging have made it possible to observe subjects performing mindfulness tasks. Objective: We set out to describe the association between mental processes and characteristics of mindfulness, including their specific cerebral patterns, as shown in structural and functional neuroimaging studies. Methods: We searched the MEDLINE databank of references and abstracts on life sciences and biomedical topics via PubMed using the keywords: "mindfulness," "focused attention (FA)," "open monitoring (OM)," "mind wandering," "emotional regulation," "magnetic resonance imaging (MRI)" and "default mode network (DMN)." This review extracted phenomenological experiences across populations with varying degrees of mindfulness training and correlated these experiences with structural and functional neuroimaging patterns. Our goal was to describe how mindful behavior was processed by the constituents of the default mode network during specific tasks. Results and conclusions: Depending on the research paradigm employed to explore mindfulness, investigations of function that used fMRI exhibited distinct activation patterns and functional connectivities. Basic to mindfulness is a long-term process of learning to use meditation techniques. Meditators progress from voluntary control of emotions and subjective preferences to emotional regulation and impartial awareness of phenomena. As their ability to monitor perception and behavior, a metacognitive skill, improves, mindfulness increases self-specifying thoughts governed by the experiential phenomenological self and reduces self-relational thoughts of the narrative self. The degree of mindfulness (ratio of self-specifying to self-relational thoughts) may affect other mental processes, e.g., awareness, working memory, mind wandering and belief formation. Mindfulness prevents habituation and the constant assumptions associated with mindlessness. Self-specifying thinking during mindfulness and self-relational thinking in the narrative self relies on the default mode network. The main constituents of this network are the dorsal and medial prefrontal cortex, and posterior cingulate cortex. These midline structures are antagonistic to self-specifying and self-relational processes, since the predominant process determines their differential involvement. Functional and brain volume changes indicate brain plasticity, mediated by mental training over the long-term.

Distinguishing transient from persistent tactile agnosia after partial anterior circulation infarcts - Behavioral and neuroimaging evidence for white matter disconnection.

From a cohort of 36 patients presenting apperceptive tactile agnosia after first cortical ischemic stroke, 14 showed temporary impairment at admission. A previous multi-voxel analysis of the cortical lesions, using as explanatory variable the course of tactile object recognition performance over the recovery period of 9 months, partitioned the cohort into three subgroups. Of the 14 patients constituting two of the subgroups, 7 recovered from their impairment whereas 7 did not. These two subgroups could not be distinguished at admission. The primary aim of the present study is to present two assessments that can do so. The first assessment comprises a pattern of behavioral measures, determined via principal component analysis, encoded in three tests: picking small objects, macrogeometrical discrimination and tactile object recognition. The receiver operating characteristic curve derived from permutation of the behavioral test scores yielded an 80% probability of correct identification of the patient subgroup and an 8% probability for false identification. As done with the permuted scores, the pattern could predict the persistence of affliction of new stroke patients with tactile agnosia. The second predictive assessment extends our previous evaluation of cortical MRI lesion maps to include subcortical regions. Confirming our previous study, the lesions of the persistently impaired subgroup disrupted significantly the anterior arcuatus fasciculus and associated superior longitudinal fasciculus III in the ipsilesional hemisphere, impeding reciprocal information transfer between supramarginal gyrus and both the ventral premotor cortex and Brodmann area 44. Due to the importance of interhemispheric information transfer in tactile agnosia, we performed a supplementary analysis of tactile object recognition scores. It showed that haptic information transfer from the non-affected to the affected hands in the persistent cases partly restored function during the nine months, possibly following restoration of functional interhemispheric haptic information transfer at the border of posterior corpus callosum and splenium. In conclusion, the combined findings of the cortical lesion at subarea PFt of the inferior parietal lobule and the associated subcortical tract lesions permit almost perfect prediction of persistent impairment of tactile object recognition. The study substantiates the need for combined analysis of both cortical lesions and white matter tract disconnections.

Sensing form - finger gaiting as key to tactile object exploration - a data glove analysis of a prototypical daily task.

BACKGROUND: Motor hand skill and associated dexterity is important for meeting the challenges of daily activity and an important resource post-stroke. In this context, the present study investigated the finger movements of right-handed subjects during tactile manipulation of a cuboid, a prototypical task underlying tactile exploration. During one motor act, the thumb and fingers of one hand surround the cuboid in a continuous and regular manner. While the object is moved by the guiding thumb, the opposed supporting fingers are replaced once they reach their joint limits by free fingers, a mechanism termed finger gaiting. METHODS: For both hands of 22 subjects, we acquired the time series of consecutive manipulations of a cuboid at a frequency of 1 Hz, using a digital data glove consisting of 29 sensors. Using principle component analysis, we decomposed the short action into motor patterns related to successive manipulations of the cuboid. The components purport to represent changing grasp configurations involving the stabilizing fingers and guiding thumb. The temporal features of the components permits testing whether the distinct configurations occur at the frequency of 1 Hz, i.e. within the time window of 1 s, and, thus, taxonomic classification of the manipulation as finger gaiting. RESULTS: The fraction of variance described by the principal components indicated that three components described the salient features of the single motor acts for each hand. Striking in the finger patterns was the prominent and varying roles of the MCP and PIP joints of the fingers, and the CMC joint of the thumb. An important aspect of the three components was their representation of distinct finger configurations within the same motor act. Principal component and graph theory analysis confirmed modular, functionally synchronous action of the involved joints. The computation of finger trajectories in one subject illustrated the workspace of the task, which differed for the right and left hands. CONCLUSION: In this task one complex motor act of 1 s duration could be described by three elementary and hierarchically ordered grasp configurations occurring at the prescribed frequency of 1 Hz. Therefore, these configurations represent finger gaiting, described until now only in artificial systems, as the principal mechanism underlying this prototypical task. TRIAL REGISTRATION: clinicaltrials.gov, NCT02865642 , registered 12 August 2016.

Early prediction of long-term tactile object recognition performance after sensorimotor stroke.

Until now tactile agnosia has been reported only in small, but detailed cross-sectional case studies. Here we show that multi-voxel pattern analysis (MVPA) of early diffusion-weighted lesion maps can be used to accurately predict long-term recovery of tactile object recognition (TOR) in 35 subjects with varying hand skill impairment and associated specific daily activity limitation after cortical sensori-motor stroke. Multiple regression analysis revealed the essentially dysfunctional subprocesses for object recognition in the specifically impaired subjects, i.e., grasping as determined by a subtest of Jebsen Taylor hand function test, and perception of macrogeometrical object properties. The Gaussian process regression of MVPA represents a function that relates a selection of lesioned voxels as input variables to TOR performance scores as target variables. On the behavioural level, patients fell into three recovery subgroups, depending on TOR performance over the observation period. Only baseline motor hand skill and shape discrimination were significantly correlated with the TOR trajectories. To define functionally meaningful voxels, we combined information from MVPA of lesion maps and a priori knowledge of regions of interest derived from a data bank for shape recognition. A high significance for the predicted TOR performances over nine months could be verified by permutation tests, leading us to expect that the model generalises to larger patient cohorts with first cortical ischemic stroke. The lesion sites of the persistently impaired subjects exhibited an overlap with critical areas related to the MVPA prediction map in the cytoarchitectonic areas PFt of inferior parietal lobule and OP1 of parietal operculum which are associated with higher order sensory processing. This ultimate check corroborated the significance of the MVPA map for the prediction of tactile object recognition. The clinical implication of our study is that neuroimaging data acquired immediately after first stroke could facilitate individual forecasting of post-stroke recovery.

Development and Validation of a Prognostic Model of Swallowing Recovery and Enteral Tube Feeding After Ischemic Stroke.

Importance: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. Objective: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. Design, Setting, and Participants: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. Exposures: Severely impaired oral intake at admission (Functional Oral Intake Scale score <5). Main Outcomes and Measures: Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke. Results: In total, 279 participants (131 women [47.0%]; median age, 77 years [interquartile range, 67-84 years]) were enrolled (153 [54.8%] in the derivation study; 126 [45.2%] in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes. Conclusions and Relevance: The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.

Relating Acute Lesion Loads to Chronic Outcome in Ischemic Stroke-An Exploratory Comparison of Mismatch Patterns and Predictive Modeling.

Objectives: To investigate the relationship between imaging features derived from lesion loads and 3 month clinical assessments in ischemic stroke patients. To support clinically implementable predictive modeling with information from lesion-load features. Methods: A retrospective cohort of ischemic stroke patients was studied. The dataset was dichotomized based on revascularization treatment outcome (TICI score). Three lesion delineations were derived from magnetic resonance imaging in each group: two clinically implementable (threshold based and fully automatic prediction) and 90-day follow-up as final groundtruth. Lesion load imaging features were created through overlay of the lesion delineations on a histological brain atlas, and were correlated with the clinical assessment (NIHSS). Significance of the correlations was assessed by constructing confidence intervals using bootstrap sampling. Results: Overall, high correlations between lesion loads and clinical score were observed (up to 0.859). Delineations derived from acute imaging yielded on average somewhat lower correlations than delineations derived from 90-day follow-up imaging. Correlations suggest that both total lesion volume and corticospinal tract lesion load are associated with functional outcome, and in addition highlight other potential areas associated with poor clinical outcome, including the primary somatosensory cortex BA3a. Fully automatic prediction was comparable to ADC threshold-based delineation on the successfully treated cohort and superior to the Tmax threshold-based delineation in the unsuccessfully treated cohort. Conclusions: The confirmation of established predictors for stroke outcome (e.g., corticospinal tract integrity and total lesion volume) gives support to the proposed methodology-relating acute lesion loads to 3 month outcome assessments by way of correlation. Furthermore, the preliminary results indicate an association of further brain regions and structures with three month NIHSS outcome assessments. Hence, prediction models might observe an increased accuracy when incorporating regional (instead of global) lesion loads. Also, the results lend support to the clinical utilization of the automatically predicted volumes from FASTER, rather than the simpler DWI and PWI lesion delineations.

The effect of a single dose of escitalopram on sensorimotor networks.

INTRODUCTION: Serving as a pilot study of poststroke pharmacotherapy, the present investigation was intended to establish the effect of a single dose of escitalopram on motor task performance in normal volunteers. METHODS: Ten healthy volunteers of median age 63 years including four females performed a well-studied tactile manipulation task in two fMRI sessions using a double-blind cross-over design. The sessions began approximately three hours after ingestion of 20 mg escitalopram or placebo presented in pseudorandom order. The fMRI image sequences were submitted to principal component analysis (PCA). RESULTS: Based on volume correlations of task-related principal components with the mean component images derived in our previous study, we established the reproducibility of two networks of sensorimotor activity proposed there. The network reflecting motor control (cerebral pattern I) appeared invariably in placebo and verum conditions. In contrast, the other network, attributed to diminished motor control due to distracting mental processing (cerebral pattern II), emerged less regularly and exhibited more variability. Second-level PCAs of both conditions confirmed the findings of the initial analysis. Specifically, it validated the dominant and invariable expression of cerebral pattern I after application of a single dose of escitalopram. Dynamic causal modeling confirmed enhanced motor output as a result of a significantly increased connectivity between primary motor cortex and dorsal premotor cortex. CONCLUSION: This pilot study suggests the promise of stimulation by a specific serotonin reuptake inhibitor in regard to recovery and preservation of motor control after stroke.

Altered praxis network underlying limb kinetic apraxia in Parkinson's disease - an fMRI study.

Parkinson's disease (PD) patients frequently suffer from dexterous deficits impeding activities of daily living. There is controversy whether impaired fine motor skill may stem from limb kinetic apraxia (LKA) rather than bradykinesia. Based on classical models of limb praxis LKA is thought to result when premotor transmission of time-space information of skilled movements to primary motor representations is interrupted. Therefore, using functional magnetic resonance imaging (fMRI) we tested the hypothesis that dexterous deficits in PD are associated with altered activity and connectivity in left parieto-premotor praxis network. Whole-brain analysis of fMRI activity during a task for LKA (coin rotation) showed increased activation of superior and inferior parietal lobule (SPL, IPL) and ventral premotor cortex (vPM) in PD patients compared to controls. For bradykinesia (assessed by finger tapping) a decreased fMRI activity could be detected in patients. Additionally, psychophysical interaction analysis showed increased functional connectivity between IPL and the posterior hippocampi in patients with PD. By contrast, functional connectivity to the right dorsolateral prefrontal cortex was decreased in patients with PD compared to controls. In conclusion, our data demonstrates that dexterous deficits in PD were associated with enhanced fMRI activation of the left praxis network upstream to primary motor areas, mirroring a neural correlate for the behavioral dissociation of LKA and bradykinesia. Furthermore, the findings suggest that patients recruit temporal areas of motor memory as an attempt to compensate for impaired motor skills. Finally, dysexecutive function may contribute to the deficit.

Diverging lesion and connectivity patterns influence early and late swallowing recovery after hemispheric stroke.

Knowledge about the recovery of oral intake after hemispheric stroke is important to guide therapeutic decisions, including the administration of enteral tube feeding and the choice of the appropriate feeding route. They aimed to determine the localization and connectivity of lesions in impaired recovery versus recovered swallowing after initially dysphagic stroke. Sixty-two acute ischemic hemispheric stroke patients with impaired oral intake were included in a prospective observational cohort study. Voxel-based lesion-symptom mapping and probabilistic tractography were used to determine the association of lesion location and connectivity with impaired recovery of oral intake ≥7 days (indication for early tube feeding) and ≥4 weeks (indication for percutaneous endoscopic gastrostomy feeding) after stroke. Two distinct patterns influencing recovery of swallowing were recognized. Firstly, impaired recovery of oral intake after ≥7 days was significantly associated with lesions of the superior corona radiata (65% of statistical map, P < 0.05). The affected fibers were connected with the thalamus, primary motor, and supplemental motor areas and the basal ganglia. Secondly, impaired recovery of oral intake after ≥4 weeks significantly correlated with lesions of the anterior insula (54% of statistical map, P < 0.05), which was connected to adjacent operculo-insular areas of deglutition. These findings indicate that early swallowing recovery is influenced by white matter lesions disrupting thalamic and corticobulbar projection fibers. Late recovery is determined by specific cortical lesions affecting association fibers. This knowledge may help clinicians to identify patients at risk of prolonged swallowing problems that would benefit from enteral tube feeding. Hum Brain Mapp 38:2165-2176, 2017. © 2017 Wiley Periodicals, Inc.

Prolonged impairment of deglutition in supratentorial ischaemic stroke: the predictive value of Parramatta Hospitals' Assessment of Dysphagia.

BACKGROUND: Up to 50% of ischaemic stroke patients show initial dysphagia, which may persist for months. Guidelines recommend switching nasogastric (NG) to percutaneous endoscopic gastrostomy (PEG) tube feeding at the second week after the stroke if impaired deglutition is expected for another 4 weeks. Precise prognostic criteria are lacking. We hypothesised that the Parramatta Hospitals' Assessment of Dysphagia (PAHD) performed 8 to 10 days after the stroke predicts impaired deglutition for another 4 weeks. METHODS: After a first dysphagia assessment (buccolingual motor function, liquid and semisolid swallow tests, "two-out-of-six" scale) within 48 hours of onset, patients with a first hemispheric stroke and risk of aspiration, defined as a two-out-of-six scale score of ≥2 (dysphonia, dysarthria, abnormal gag reflex, abnormal volitional cough, cough / voice change after swallowing) were included and were assessed by a blinded rater using the PHAD. The same dysphagia assessments were repeated 8 to 10 days after the stroke (second assessment) and patients remained in the study if the two-out-of-six scale score remained ≥2. At a final evaluation by telephone after 4 weeks, impaired deglutition was assessed with the Bogenhausen dysphagia score (BODS-2). Exclusion criteria were infratentorial or recurrent stroke and pre-existing dysphagia. The primary objective was to define a threshold score and value of the PHAD at second assessment that predicted impaired deglutition as assessed with the BODS-2 (score ≥4) at the final evaluation. The secondary objective was to explore the value of the PHAD assessed within 48 hours to predict impaired deglutition (BODS-2 ≥4) at final evaluation. To evaluate the predictive value of the PHAD score assessed 8 to 10 days after stroke onset for impaired deglutition for another 4 weeks, we determined the area under the receiver operating curve (ROC AUC). RESULTS: Over a 1-year period, 29 out of 252 assessed patients remained at risk of aspiration after the second assessment. In these patients, ROC analysis of PHAD recorded 8 to 10 days after the stroke showed excellent accuracy with an AUC of 0.971 (cut-off 71.5) predicting a BODS-2 score of ≥4 at final evaluation. The accuracy of ROC analysis of the PHAD score assessed within 48 hours of stroke onset to predict prolonged impairment of deglutition was poor (AUC 0.685). CONCLUSIONS: In a selected population at risk of aspiration, the PHAD with a threshold of 70 assessed in the second week after stroke onset may be a valuable tool to predict prolonged impairment of deglutition for another 4 weeks and to guide the decision about switching from NG to PEG tube feeding after supratentorial ischaemic stroke.

Supplementary Motor Complex and Disturbed Motor Control - a Retrospective Clinical and Lesion Analysis of Patients after Anterior Cerebral Artery Stroke.

BACKGROUND: Both the supplementary motor complex (SMC), consisting of the supplementary motor area (SMA) proper, the pre-SMA, and the supplementary eye field, and the rostral cingulate cortex are supplied by the anterior cerebral artery (ACA) and are involved in higher motor control. The Bereitschaftspotential (BP) originates from the SMC and reflects cognitive preparation processes before volitional movements. ACA strokes may lead to impaired motor control in the absence of limb weakness and evoke an alien hand syndrome (AHS) in its extreme form. AIM: To characterize the clinical spectrum of disturbed motor control after ACA strokes, including signs attributable to AHS and to identify the underlying neuroanatomical correlates. METHODS: A clinical assessment focusing on signs of disturbed motor control including intermanual conflict (i.e., bilateral hand movements directed at opposite purposes), lack of self-initiated movements, exaggerated grasping, motor perseverations, mirror movements, and gait apraxia was performed. Symptoms were grouped into (A) AHS-specific and (B) non-AHS-specific signs of upper limbs, and (C) gait apraxia. Lesion summation mapping was applied to the patients' MRI or CT scans to reveal associated lesion patterns. The BP was recorded in two patients. RESULTS: Ten patients with ACA strokes (nine unilateral, one bilateral; mean age: 74.2 years; median NIH-SS at admission: 13.0) were included in this case series. In the acute stage, all cases had marked difficulties to perform volitional hand movements, while movements in response to external stimuli were preserved. In the chronic stage (median follow-up: 83.5 days) initiation of voluntary movements improved, although all patients showed persistent signs of disturbed motor control. Impaired motor control is predominantly associated with damaged voxels within the SMC and the anterior and medial cingulate cortex, while lesions within the pre-SMA are specifically related to AHS. No BP was detected over the damaged hemisphere. CONCLUSION: ACA strokes involving the premotor cortices, particularly the pre-SMA, are associated with AHS-specific signs. In the acute phase, motor behavior is characterized by the inability to carry out self-initiated movements. Motor control deficits may persist to a variable degree beyond the acute phase. Alterations of the BP point to an underlying SMC dysfunction in AHS.

A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM: To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS: Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS: Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION: Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss Young Stroke Study (SYSS).

Ischaemic stroke (IS) in young adults has been increasingly recognized as a serious health condition. Stroke aetiology is different in young adults than in the older population. This study aimed to investigate aetiology and risk factors, and to search for predictors of outcome and recurrence in young IS patients. We conducted a prospective multicentre study of consecutive IS patients aged 16-55 years. Baseline demographic data, risk factors, stroke aetiology including systematic genetic screening for Fabry disease and severity were assessed and related to functional neurological outcome (modified Rankin Scale, mRS), case fatality, employment status, place of residence, and recurrent cerebrovascular events at 3 months. In 624 IS patients (60% men), median age was 46 (IQR 39-51) years and median NIHSS on admission 3 (IQR 1-8). Modifiable vascular risk factors were found in 73%. Stroke aetiology was mostly cardioembolism (32%) and of other defined origin (24%), including cervicocerebral artery dissection (17%). Fabry disease was diagnosed in 2 patients (0.3%). Aetiology remained unknown in 20%. Outcome at 3 months was favourable (mRS 0-1) in 61% and fatal in 2.9%. Stroke severity (p < 0.001) and diabetes mellitus (p = 0.023) predicted unfavourable outcome. Stroke recurrence rate at 3 months was 2.7%. Previous stroke or TIA predicted recurrent cerebrovascular events (p = 0.012). In conclusion, most young adults with IS had modifiable vascular risk factors, emphasizing the importance of prevention strategies. Outcome was unfavourable in more than a third of patients and was associated with initial stroke severity and diabetes mellitus. Previous cerebrovascular events predicted recurrent ones.

Interhemispheric cerebral blood flow balance during recovery of motor hand function after ischemic stroke--a longitudinal MRI study using arterial spin labeling perfusion.

BACKGROUND: Unilateral ischemic stroke disrupts the well balanced interactions within bilateral cortical networks. Restitution of interhemispheric balance is thought to contribute to post-stroke recovery. Longitudinal measurements of cerebral blood flow (CBF) changes might act as surrogate marker for this process. OBJECTIVE: To quantify longitudinal CBF changes using arterial spin labeling MRI (ASL) and interhemispheric balance within the cortical sensorimotor network and to assess their relationship with motor hand function recovery. METHODS: Longitudinal CBF data were acquired in 23 patients at 3 and 9 months after cortical sensorimotor stroke and in 20 healthy controls using pulsed ASL. Recovery of grip force and manual dexterity was assessed with tasks requiring power and precision grips. Voxel-based analysis was performed to identify areas of significant CBF change. Region-of-interest analyses were used to quantify the interhemispheric balance across nodes of the cortical sensorimotor network. RESULTS: Dexterity was more affected, and recovered at a slower pace than grip force. In patients with successful recovery of dexterous hand function, CBF decreased over time in the contralesional supplementary motor area, paralimbic anterior cingulate cortex and superior precuneus, and interhemispheric balance returned to healthy control levels. In contrast, patients with poor recovery presented with sustained hypoperfusion in the sensorimotor cortices encompassing the ischemic tissue, and CBF remained lateralized to the contralesional hemisphere. CONCLUSIONS: Sustained perfusion imbalance within the cortical sensorimotor network, as measured with task-unrelated ASL, is associated with poor recovery of dexterous hand function after stroke. CBF at rest might be used to monitor recovery and gain prognostic information.

Symptomatic intracranial hemorrhage after stroke thrombolysis: comparison of prediction scores.

BACKGROUND AND PURPOSE: Several prognostic scores have been developed to predict the risk of symptomatic intracranial hemorrhage (sICH) after ischemic stroke thrombolysis. We compared the performance of these scores in a multicenter cohort. METHODS: We merged prospectively collected data of patients with consecutive ischemic stroke who received intravenous thrombolysis in 7 stroke centers. We identified and evaluated 6 scores that can provide an estimate of the risk of sICH in hyperacute settings: MSS (Multicenter Stroke Survey); HAT (Hemorrhage After Thrombolysis); SEDAN (blood sugar, early infarct signs, [hyper]dense cerebral artery sign, age, NIH Stroke Scale); GRASPS (glucose at presentation, race [Asian], age, sex [male], systolic blood pressure at presentation, and severity of stroke at presentation [NIH Stroke Scale]); SITS (Safe Implementation of Thrombolysis in Stroke); and SPAN (stroke prognostication using age and NIH Stroke Scale)-100 positive index. We included only patients with available variables for all scores. We calculated the area under the receiver operating characteristic curve (AUC-ROC) and also performed logistic regression and the Hosmer-Lemeshow test. RESULTS: The final cohort comprised 3012 eligible patients, of whom 221 (7.3%) had sICH per National Institute of Neurological Disorders and Stroke, 141 (4.7%) per European Cooperative Acute Stroke Study II, and 86 (2.9%) per Safe Implementation of Thrombolysis in Stroke criteria. The performance of the scores assessed with AUC-ROC for predicting European Cooperative Acute Stroke Study II sICH was: MSS, 0.63 (95% confidence interval, 0.58-0.68); HAT, 0.65 (0.60-0.70); SEDAN, 0.70 (0.66-0.73); GRASPS, 0.67 (0.62-0.72); SITS, 0.64 (0.59-0.69); and SPAN-100 positive index, 0.56 (0.50-0.61). SEDAN had significantly higher AUC-ROC values compared with all other scores, except for GRASPS where the difference was nonsignificant. SPAN-100 performed significantly worse compared with other scores. The discriminative ranking of the scores was the same for the National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke definitions, with SEDAN performing best, GRASPS second, and SPAN-100 worst. CONCLUSIONS: SPAN-100 had the worst predictive power, and SEDAN constantly the highest predictive power. However, none of the scores had better than moderate performance.

Validation of the DRAGON score in 12 stroke centers in anterior and posterior circulation.

BACKGROUND AND PURPOSE: The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0-2) and miserable (modified Rankin scale score, 5-6) outcomes. RESULTS: Area under the receiver operating characteristic curve was 0.84 (0.82-0.85) for miserable outcome and 0.82 (0.80-0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83-0.86) and 0.82 (0.78-0.87), respectively. No sex-related difference in performance was observed (P=0.25). CONCLUSIONS: The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

BACKGROUND AND PURPOSE: We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. RESULTS: In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS: I.v. thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Relationship between onset-to-door time and door-to-thrombolysis time: a pooled analysis of 10 dedicated stroke centers.

BACKGROUND AND PURPOSE: Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers. METHODS: Prospectively collected data of consecutive ischemic stroke patients from 10 centers who received IV thrombolysis within 4.5 hours from symptom onset were merged (n=7106). DNT was analyzed as a function of demographic and prehospital variables using regression analyses, and change over time was considered. RESULTS: In 6348 eligible patients with known treatment delays, median DNT was 42 minutes and kept decreasing steeply every year (P<0.001). Median DNT of 55 minutes was observed in patients with ODT ≤30 minutes, whereas it declined for patients presenting within the last 30 minutes of the 3-hour time window (median, 33 minutes) and of the 4.5-hour time window (20 minutes). For ODT within the first 30 minutes of the extended time window (181-210 minutes), DNT increased to 42 minutes. DNT was stable for ODT for 30 to 150 minutes (40-45 minutes). We found a weak inverse overall correlation between ODT and DNT (R(2)=-0.12; P<0.001), but it was strong in patients treated between 3 and 4.5 hours (R(2)=-0.75; P<0.001). ODT was independently inversely associated with DNT (P<0.001) in regression analysis. Octogenarians and women tended to have longer DNT. CONCLUSIONS: DNT was decreasing steeply over the last years in dedicated stroke centers; however, significant oscillations of in-hospital treatment delays occurred at both ends of the time window. This suggests that further improvements can be achieved, particularly in the elderly.