Search

Motor hand deficits impact autonomy in everyday life, and neuroplasticity processes of motor recovery can be explored using functional MRI (fMRI). However, few studies have used fMRI to explore the mechanisms underlying hand recovery following stroke. Based on the dual visuomotor model positing that two segregated dorsomedial and dorsolateral cerebral networks control reach and grasp movements, we explored the relationship between motor task-related activity in the sensorimotor network and hand recovery following stroke. Behavioral recovery was explored with a handgrip force task assessing simple grasp, and a visuomotor reaching and precise grasping task, the Purdue Pegboard Test (PPT). We used a passive wrist flexion-extension task to measure fMRI activity in 36 sensorimotor brain areas. Behavioral and fMRI measurements were performed in 27 patients (53.2 ± 9.5 years) 1-month following stroke, and then 6-month and 24-month later. The effects of sensorimotor activity on hand recovery were analyzed using correlations and linear mixed models (LMMs). PPT and handgrip force correlated with fMRI activity measures in the sensorimotor and parietal areas. PPT recovery was modeled by fMRI measures in the ipsilesional primary motor cortex (MI-4p), superior parietal lobule (SPL-7M) and parietal operculum OP1, and lesion side. Handgrip force was modeled by ipsilesional MI-4a, OP1, and contralesional inferior parietal lobule (IPL-PFt). Moreover, the relationship between fMRI activity and hand recovery was time-dependent, occurring in the early recovery period in SPL-BA-7M, and later in MI. These results suggest that areas of both dorsolateral and dorsomedial networks participate to visuomotor reach and grasp tasks (PPT), while dorsolateral network areas may control recovery of simple grasp (handgrip force), suggesting that the type of movement modulates network recruitment. We also found functional dissociations between MI-4p related to PPT that required independent finger movements and MI-4a related to simple grasp without independent finger movements. These findings need to be replicated in further studies.

ObjectiveTo identify candidate biomarkers of walking recovery with motor tract integrity measurements using fractional anisotropy (FA) from the corticospinal tract (CST) and alternative motor pathways in patients with moderate to severe subacute stroke.MethodsWalking recovery was first assessed with generalized linear mixed model (GLMM) with repeated measures of walking scores (WS) over 2 years of follow-up in a longitudinal study of 29 patients with subacute ischemic stroke. Baseline FA measures from the ipsilesional and contralesional CST (i-CST and c-CST), cortico-reticulospinal pathway (i-CRP and c-CRP), and cerebellar peduncles were derived from a 60-direction diffusion MRI sequence on a 3T scanner. We performed correlation tests between WS and FA measures. Third, we investigated using GLMM whether motor tract integrity contributes to predict walking recovery.ResultsWe observed significant improvements of WS over time with a plateau reached at ≈6 months after stroke. WS significantly correlated with FA measures from i-CST, c-CST, i-CRP, and bilateral cerebellar peduncles. Walking recovery was predicted by FA measures from 3 tracts: i-CST, i-CRP, and contralesional superior cerebellar peduncle (c-SCP). Diffusion tensor imaging (DTI) predictors captured 80.5% of the unexplained variance of the model without DTI.ConclusionsWe identified i-CST and alternative motor-related tracts (namely i-CRP and c-SCP) as candidate biomarkers of walking recovery. The role of the SCP in walk recovery may rely on cerebellar nuclei projections to the thalamus, red nucleus, and reticular formation. Our findings suggest that a set of white matter tracts, part of subcortical motor networks, contribute to walking recovery in patients with moderate to severe stroke.

Although less-affected hand (LAH) deficits following unilateral stroke are well documented, many aspects of LAH impairment mechanisms remain unresolved. To provide a better understanding of these mechanisms, we used diffusion MRI to examine the disruptions of white matter structural connections. Based on the redundancy theory, we hypothesized that a summation of motor-related tract disruptions would characterize LAH impairment. We assessed LAH impairment and fractional anisotropy (FA) in 28 patients at one-month post-stroke (baseline), and 6 and 24 months later. LAH impairment was assessed with the Purdue Pegboard Test (PPT), handgrip strength, and movement time. FA was estimated in the CST, Anterior- Corona Radiata (ACR), and Limb of Internal Capsule (ALIC), Superior Longitudinal Fasciculus (SLF), and corpus callosum (CC). We used Linear Mixed Models to determine the tracts associated with LAH impairment over time. Baseline PPT, grip, and movement time were impaired in 43%, 61%, and 25%, respectively. PPT was modeled by baseline ipsilesional-CST (t=3.75; p

Lacunar stroke is a common subtype of stroke, comprising 20%–25% of ischemic strokes, linking a number of clinical syndromes to occlusion of a single perforating artery (40–900 μm in diameter) resulting from vasculopathy characterized by lipohyalinosis, arteriolosclerosis, and microatheroma. Hypertension is the leading cause, along with atherosclerosis and other stroke risk factors.1-3 Lacunes may be described as small deep cerebral infarcts, 3–17 mm in maximum diameter, located in cerebral hemisphere and brainstem regions supplied by perforating arteries.4 The term lacune stems from the French literature in the 19th century to describe, based on anatomical examination, small cavities with liquefaction necrosis.

Background: Tinnitus and its mechanisms are an ongoing subject of interrogation in the neuroscientific community. Although most current models agree that it encompasses multiple structures within and outside the auditory system, evidence provided in the literature suffers from a lack of convergence. To further our understanding of contributions to tinnitus lying outside the auditory system, we explored a new model based on a proprioceptive hypothesis specifically in subjects experiencing chronic nonbothersome tinnitus due to acoustic trauma. The present study addresses the role of the right operculum 3 (OP3) involved in this model. It also investigates classical models of tinnitus. Methods: A seed-based resting-state magnetic resonance imaging study explored the functional connectivity in an acoustic trauma group presenting slight to mild nonbothersome chronic tinnitus and compared it with a control group. Results: Group differences were found with two networks: with the sensorimotor-auditory and the frontoparietal, but not with the default mode network nor the limbic regions. In the auditory pathway, the inferior colliculus displayed group differences in connectivity with the right superior parietal lobule. Exploratory analysis elicited a significant increase in connectivity between two seeds in the right OP3 and two mirror regions of the dorsal prefrontal cortex, thought to correspond to the human homologue of the premotor ear-eye field bilaterally and the inferior parietal lobule involved in proprioception, in the tinnitus group. Conclusions: These new findings support the view that acoustic trauma tinnitus could bear a proprioceptive contribution and that a permanent cognitive control is required to filter out this chronic phantom percept.

Background Cell therapy is promising in experimental studies and has been assessed only in a few studies on humans. Aims To evaluate the effect of cell therapy in humans. Methods We included clinical trials with a control group that reported safety and efficacy six months following treatment. Quality was evaluated and clinical scales data were extracted. Quantitative analysis was based on the standardized means difference (SMD). Among 28 trials published from 1995 to 2016, nine studies (194 patients; 191 controls) were eligible. Publication biases were assessed with the funnel plot and pre-specified explanatory variables were tested with a group analysis and a meta-regression. Results The overall quality was moderate. Cell therapy had a positive effect on the outcome (SMD: 0.57, 95% CI: 0.22–0.92; p = 0.002). The sensitivity analysis showed an upper level of effect size of 0.81 (95% CI: 0.34–1.27; p = 0.001) and a lower level of 0.455 (95% CI: 0.04–0.87; p = 0.03). None of the pre-specified explanatory variable was significantly correlated to outcome: age, ratio infarction/hemorrhage, delay from stroke to treatment, route of administration, cell type, randomization, and blinded outcome assessment. The significant heterogeneity (p = 0.03) was not explained by publication biases (p = 0.09) and was more likely due to methodological and quality differences between the trials. Conclusions This result suggests that cell therapy is beneficial in stroke and is expected to help in the designing of stem cells controlled clinical trials (CCT) in large populations.

While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation. During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cerebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), putamen and ipsilesional OP1 predicted motor outcome measured 6 months later (adjusted-R2 = 0.85; bootstrap p, Highlights • Motor recovery after stroke can be robustly predicted using a passive task fMRI paradigm. • Sensorimotor network activity is decreased in moderate to severe stroke patients relative to healthy controls • Compensatory mechanisms in severe stroke involve both the dorsal (MI BA4a), and the ventral (OP1 and OP4) sensorimotor stream

International audience; We evaluated the effect of normal aging on the inter-hemispheric processing of semantic information by using the divided visual field (DVF) method, with words and pictures. Two main theoretical models have been considered, (a) the HAROLD model which posits that aging is associated with supplementary recruitment of the right hemisphere (RH) and decreased hemispheric specialization, and (b) the RH decline theory, which assumes that the RH becomes less efficient with aging, associated with increased LH specialization. Two groups of subjects were examined, a Young Group (YG) and an Old Group (OG), while participants performed a semantic categorization task (living vs. non-living) in words and pictures. The DVF was realized in two steps: (a) unilateral DVF presentation with stimuli presented separately in each visual field, left or right, allowing for their initial processing by only one hemisphere, right or left, respectively; (b) bilateral DVF presentation (BVF) with stimuli presented simultaneously in both visual fields, followed by their processing by both hemispheres. These two types of presentation permitted the evaluation of two main characteristics of the inter-hemispheric processing of information, the hemispheric specialization (HS) and the inter-hemispheric cooperation (IHC). Moreover, the BVF allowed determining the driver-hemisphere for processing information presented in BVF. Results obtained in OG indicated that: (a) semantic categorization was performed as accurately as YG, even if more slowly, (b) a non-semantic RH decline was observed, and (c) the LH controls the semantic processing during the BVF, suggesting an increased role of the LH in aging. However, despite the stronger involvement of the LH in OG, the RH is not completely devoid of semantic abilities. As discussed in the paper, neither the HAROLD nor the RH decline does fully explain this pattern of results. We rather suggest that the effect of aging on the hemispheric specialization and inter-hemispheric cooperation during semantic processing is explained not by only one model, but by an interaction between several complementary mechanisms and models.

Tinnitus mechanisms remain poorly understood. Our previous functional MRI (fMRI) studies demonstrated an abnormal hyperactivity in the right parietal operculum 3 (OP3) in acoustic trauma tinnitus and during provoked phantom sound perceptions without hearing loss, which lead us to propose a new model of tinnitus. This new model is not directly linked with hearing loss and primary auditory cortex abnormalities, but with a proprioceptive disturbance related to middle-ear muscles. In the present study, a seed-based resting-state functional MRI method was used to explore the potential abnormal connectivity of this opercular region between an acoustic trauma tinnitus group presenting slight to mild tinnitus and a control group. Primary auditory cortex seeds were also explored because they were thought to be directly involved in tinnitus in most current models. In such a model, hearing loss and tinnitus handicap were confounding factors and were therefore regressed in our analysis. Between-groups comparisons showed a significant specific connectivity between the right OP3 seeds and the potential human homologue of the premotor ear-eye field (H-PEEF) bilaterally and the inferior parietal lobule (IPL) in the tinnitus group. Our findings suggest the existence of a simultaneous premotor ear-eye disturbance in tinnitus that could lift the veil on unexplained subclinical abnormalities in oculomotor tests found in tinnitus patients with normal vestibular responses. The present work confirms the involvement of the OP3 subregion in acoustic trauma tinnitus and provides some new clues to explain its putative mechanisms.

International audience; The rehabilitation of speech disorders benefits from providing visual information which may improve speech motor plans in patients. We tested the proof of concept of a rehabilitation method (Sensori-Motor Fusion, SMF; Ultraspeech player) in one post-stroke patient presenting chronic non-fluent aphasia. SMF allows visualisation by the patient of target tongue and lips movements using high-speed ultrasound and video imaging. This can improve the patient?s awareness of his/her own lingual and labial movements, which can, in turn, improve the representation of articulatory movements and increase the ability to coordinate and combine articulatory gestures. The auditory and oro-sensory feedback received by the patient as a result of his/her own pronunciation can be integrated with the target articulatory movements they watch. Thus, this method is founded on sensorimotor integration during speech. The SMF effect on this patient was assessed through qualitative comparison of language scores and quantitative analysis of acoustic parameters measured in a speech production task, before and after rehabilitation. We also investigated cerebral patterns of language reorganisation for rhyme detection and syllable repetition, to evaluate the influence of SMF on phonological-phonetic processes. Our results showed that SMF had a beneficial effect on this patient who qualitatively improved in naming, reading, word repetition and rhyme judgment tasks. Quantitative measurements of acoustic parameters indicate that the patient?s production of vowels and syllables also improved. Compared with pre-SMF, the fMRI data in the post-SMF session revealed the activation of cerebral regions related to articulatory, auditory and somatosensory processes, which were expected to be recruited by SMF. We discuss neurocognitive and linguistic mechanisms which may explain speech improvement after SMF, as well as the advantages of using this speech rehabilitation method.

BACKGROUND: Diffusion tensor imaging has been widely used to measure HIV effects on white matter microarchitecture. While many authors have reported reduced fractional anisotropy and increased mean diffusivity in HIV, quantitative inconsistencies across studies are numerous. PURPOSE: Our aim was to evaluate the consistency across studies of HIV effects on DTI measures and then examine the DTI reliability in a longitudinal seropositive cohort. DATA SOURCES: Published studies and investigators. STUDY SELECTION: The meta-analysis included 16 cross-sectional studies reporting fractional anisotropy and 12 studies reporting mean diffusivity in the corpus callosum. DATA ANALYSIS: Random-effects meta-analysis was used to estimate study standardized mean differences and heterogeneity. DTI longitudinal reliability was estimated in seropositive participants studied before and 3 and 6 months after beginning treatment. DATA SYNTHESIS: Meta-analysis revealed lower fractional anisotropy (standardized mean difference, −0.43; P 0.96. LIMITATIONS: Many studies pooled participants with varying treatments, ages, and disease durations. CONCLUSIONS: HIV effects on WM microstructure had substantial variations that could result from acquisition, processing, or cohort-selection differences. When acquisition parameters and processing were carefully controlled, the resulting DTI measures did not show high temporal variation. HIV effects on WM microstructure may be age-dependent. The high longitudinal reliability of DTI WM microstructure measures makes them promising disease-activity markers.

International audience; Stroke, resulting in focal structural damage, induces changes in brain function at both local and global levels. Following stroke, cerebral networks present structural, and functional reorganization to compensate for the dysfunctioning provoked by the lesion itself and its remote effects. As some recent studies underlined the role of the contralesional hemisphere during recovery, we studied its role in the reorganization of brain function of stroke patients using resting state fMRI and graph theory. We explored this reorganization using the "hub disruption index" (κ), a global index sensitive to the reorganization of nodes within the graph. For a given graph metric, κ of a subject corresponds to the slope of the linear regression model between the mean local network measures of a reference group, and the difference between that reference and the subject under study. In order to translate the use of κ in clinical context, a prerequisite to achieve meaningful results is to investigate the reliability of this index. In a preliminary part, we studied the reliability of κ by computing the intraclass correlation coefficient in a cohort of 100 subjects from the Human Connectome Project. Then, we measured intra-hemispheric κ index in the contralesional hemisphere of 20 subacute stroke patients compared to 20 age-matched healthy controls. Finally, due to the small number of patients, we tested the robustness of our results repeating the experiment 1000 times by bootstrapping on the Human Connectome Project database. Statistical analysis showed a significant reduction of κ for the contralesional hemisphere of right stroke patients compared to healthy controls. Similar results were observed for the right contralesional hemisphere of left stroke patients. We showed that κ, is more reliable than global graph metrics and more sensitive to detect differences between groups of patients as compared to healthy controls. Using new graph metrics as κ allows us to show that stroke induces a network-wide pattern of reorganization in the contralesional hemisphere whatever the side of the lesion. Graph modeling combined with measure of reorganization at the level of large-scale networks can become a useful tool in clinic.

Introduction/Background The sense of verticality results from a complex multisensory integration suggesting the existence of internal models of verticality perception. Recent data from our team suggest that the parietal operculum, the posterior insula and the posterior-lateral thalamus, in the right hemisphere, constitute the core polymodal regions that construct and update the internal models of verticality. The aim of this study was double. First, to analyse functional connectivity, in a group of healthy participants, of the three core regions in a larger verticality perception network, established on literature data. Second, to analyse functional connectivity of these three regions in a group of stroke patients presenting an altered perception of verticality. Material and method Functional connectivity was studied using ROI-to-ROI method in Connectivity toolbox with resting state functional Magnetic Resonance Imaging (fMRI). The regions of interest were selected from Anatomy toolbox, with source regions OP1, OP2, Ig1, Ig2, parietal and somatosensory thalamus. The first study concerned 74 healthy participants and the second study concerned 5 stroke patients with altered verticality perception in visual modality. Results In the healthy participants group, the three regions (represented by OP1, OP2, Ig1, Ig2, ThP and ThS) constitute a highly connected network in both hemispheres. In stroke patients group, this network was globally preserved in the healthy hemisphere, but disrupted in the brain-damaged hemisphere. Moreover, we observed a correlation between the loss of inter-hemispheric connectivity within this network and the altered perception of verticality in the visual modality. Conclusion The parietal operculum, the posterior insula and the posterior-lateral thalamus form a network that could correspond to the ‘sense of upright’ network.

In the last decade, functional MRI (fMRI) has become one of the most widely used functional imaging technique in neurosciences. However, its clinical applications remain limited. Despite methodological and practical issues, fMRI data has been validated by different techniques (magnetoencephalography, Wada test, electrical and magnetic stimulations, and surgical resections). In neurosurgical practice, fMRI can identify eloquent areas involved in motor and language functions, and may evaluate characteristics of postoperative neurological deficit including its occurrence, clinical presentation and duration. This may help to inform patients and to prepare postoperative care. fMRI may also identify epileptic foci. In neurological practice, fMRI may help to determine prognosis of recovery after stroke, appropriate medication, and rehabilitation. fMRI may help to identify patients at risk of developing Alzheimer disease. Finally, cerebrovascular reactivity imaging is an interesting approach that might provide new radiological insights of vascular function.

Background: Little is known about the relationship between hypercholesterolaemia and specific aetiological subtypes of brain infarction (BI). Methods: In a cross-sectional study of 492 pairs of patients with a BI proven by MRI and matched hospital controls, we determined the blood levels of triglycerides, total, HDL and LDL cholesterol, and apolipoprotein A1 and B, in the same centralized laboratory. We performed aetiological BI subtype classification. Results: Except for triglycerides, the risk of BI increased continuously with the lipid levels, without any heterogeneity between the main BI subtypes or the group on lipid-lowering therapy. The adjusted odds ratio per standard deviation in LDL cholesterol (0.93 mmol/l) was 1.74 (95% confidence interval, 1.02–2.98) in atherothrombotic strokes (n = 109) and 2.71 (95% confidence interval, 1.60–4.55) in lacunar strokes (n = 105). Eighty percent of patients were above the ATP-III guideline threshold LDL cholesterol of 2.59 mmol/l (100 mg/dl), with a major contribution of both atherothrombotic and lacunar stroke subtypes to this group. Conclusions: These findings suggest that blood lipids, particularly total and LDL cholesterol levels, are associated with all subtypes of BI, and that LDL above 2.59 mmol/l is highly prevalent.

International audience; ObjectiveTo assess the efficiency of Visual Feedback (VF) on language recovery and plasticity in three chronic non-fluent aphasic patients. VF is based on language-action interaction, thus, language skills are improved by rehabilitation strategies based on execution and observation of motor actions. VF is an ultrasound system coupled with video images, allowing patients to ‘see their own lips and tongue at work’ during speech and improve their awareness of their lingual and labial movements and their ability to coordinate and combine phonemes and syllables. Brain plasticity was explored with functional MRI.Material/Patients and methods– Control group tested with functional MRI to identify language networks underlying three tasks of interest;– three patients with non-fluent chronic aphasia after ischemic stroke, were examined in neuropsychology, speech therapy, acoustics and fMRI, before and after VF. VF has been applied during 14 sessions (2 weeks, 1 per day). The performance was evaluated before and after VF. In fMRI, specific comparisons were performed to identify: – patterns of reorganization reflecting spontaneous neuro-plasticity, – the effect of VF on speech recovery and language plasticity.ResultsAfter 14 sessions of VF, acoustic analyses showed a more canonical vowel production and better repetition of consonants. Speech analysis for repetition of syllables, naming and rhytme judgment, showed a general improvement of performances, variable among patients. In terms of cerebral activation, various patterns of language reorganization were obtained according to task and level of language recovery. A general trend can be identified with the improvement of language performance after VF, which is a right hemispheric predominance before VF, followed by a return of the activity to the left hemisphere, after VF.Discussion - ConclusionResults are discussed according to current models of inter and intra-hemispheric reorganization of language.

Background and Purpose— Although neuroimaging studies have revealed specific patterns of reorganization in the sensorimotor control network after stroke, their role in recovery remains unsettled. To review the existing evidence systematically, we performed activation likelihood estimation meta-analysis of functional neuroimaging studies investigating upper limb movement-related brain activity after stroke. Methods— Twenty-four studies using sensorimotor tasks in standardized coordinates were included, totaling 255 patients and 145 healthy controls. Across the entire brain, we compared task-related activity patterns in good and poor recovery and assessed the magnitude of spatial shifts in sensorimotor activity in cortical motor areas after stroke. Results— When compared with healthy controls, patients showed higher activation likelihood estimation values in contralesional primary motor soon after stroke that abated with time, but were not related to motor outcome. The observed activity changes were consistent with restoration of typical interhemispheric balance. In contrast, activation likelihood estimation values in ipsilesional medial-premotor and primary motor cortex were associated with good outcome, reorganization that may reflect vicarious processes associated with ventral activity shifts from BA4a to 4p. In the anterior cerebellum, a novel finding was the association of poor recovery with increased vermal activity, possibly reflecting behaviorally inadequate compensatory strategies engaging the fastigio-thalamo-cortical and corticoreticulospinal systems. Conclusions— Activity in ipsilesional primary motor and medial-premotor cortices in chronic stroke signals good motor recovery, whereas cerebellar vermis activity signals poor recovery. Functional MRI may be useful in identifying recovery biomarkers.

Background and Purpose —Three major randomized controlled trials of streptokinase in acute ischemic stroke were curtailed because of safety concerns. The prospective Thrombolysis in Acute Stroke Pooling Project (TAS-PP) was established to examine the aggregate data to identify factors influencing the effect of streptokinase. Methods —Individual patient data from the Australian Streptokinase Trial (ASK), Multicentre Acute Stroke Trial-Europe (MAST-E), Multicentre Acute Stroke Trial-Italy (MAST-I), and Glasgow Trial (Glasgow) were pooled. Multivariate modeling determined the interaction between treatment effect and delay from symptom onset to treatment, predicted baseline risk, age, concomitant aspirin or heparin use, and the presence of early CT signs on the outcomes of 10-day death, death and disability, or death alone at 3 or 6 months. Results —Patients’ records were pooled (total 1292 patients; streptokinase, n=653, no streptokinase n=639). The subgroup analysis of treatment effect according to delay from symptoms to inclusion shows only a trend toward a better treatment effect with shorter delay, which is not statistically significant for any outcome. Heavier patients in MAST-E may have had a lower (non significant) risk from the fixed dose of 1.5 million units of streptokinase. Concomitant aspirin increased the excess mortality rates in streptokinase-treated patients (17% without aspirin versus 91% with aspirin, P =0.005). The presence of early CT scan signs did not increase the detrimental effect of streptokinase. Conclusions —Few factors influenced the response to streptokinase. However, earlier administration, lower doses of streptokinase, and avoidance of concomitant aspirin should be considered if further streptokinase trials in acute stroke are planned.

A door-to-door population-based epidemiological study of the prevalence of migraine and headache in a sample of 3246 people older than 15 years of age was carried out in Cuzco, a high-altitude town in the Peruvian Andes, located at 3380 meters. Among the 3246 screened people, there were 172 cases of migraine and 930 cases of headache, yielding a crude 1-year prevalence of 5.3% for migraine (2.3% among men and 7.8% among women) and 28.7% for headache (17.5% among men and 38.2% among women). Our results suggest that migraine prevalence in Cuzco is close to that of other developing countries, whereas headache prevalence may be higher than in other developing countries. Multivariate logistic regression suggested that both migraine and headache were related to the female sex, age, and anxiety and/or depression. This study suggests that migraine is a relatively common disorder in Cuzco, but does not show any difference which could be significantly related to altitude. In contrast, our results suggest that headache may be more frequent at high altitude than at sea level.

Background Poststroke depression and cognitive dysfunction are common and are independent predictors of poor recovery. Aims We assessed whether and how depression and cognition were correlated in the subacute period after stroke. Method We prospectively recruited 207 nondemented patients (Mini Mental State Examination ≥ 23) presenting with a first-ever ischemic stroke (127 males), mean age of 48·5 years (16·4 standard deviation), median 12 days after infarction, as assessed on magnetic resonance imaging. We administered a comprehensive neuropsychological battery involving cognitive domains including instrumental functions, memory, executive functions, and working memory. Depression was quantified with the Beck Depression Inventory. Results Depression (Beck Depression Inventory > 9) was identified in 30·4% of the patients (95% confidence interval 24·2–37·2%). Median Beck Depression Inventory was 6. Median Mini Mental State Examination was 30. Cognitive dysfunctioning in at least one neuropsychological test was present in 89% (95% confidence interval 84–93%). Each point increase of Beck Depression Inventory was associated with an odd of 1·1 (95% confidence interval 1·04–1·19) of changing to a worse category of cognition. Stroke location was not correlated with depression. All cognitive domains were significantly correlated with depression. In multivariate analysis, the executive functions ( P = 0·001) and the working memory ( P = 0·009) were the best predictors of depression when adjusted for demographic and stroke characteristics. Conclusions The rates of depression and cognitive impairment were in the range of previous stroke studies. Our study suggested a strong relation between depression and cognition characterized by executive functions and working memory dysfunctioning.

The French healthcare system is organised according to a political, geographical and demographic framework. In France today, less than 20 hospitals have dedicated intensive care units for acute stroke patients. In the 1999 national survey, 94% of stroke patients were admitted to public hospitals, 35% were treated in neurological wards and 4% had access to an intensive care stroke unit. To improve the quality of care and resource utilisation, a national plan for stroke will be implemented at regional level during the next five-year plan. After a long period of status quo, many positive actions for stroke care have been initiated within a couple of years, based on the evidence of more effective stroke treatments, such as thrombolysis and the specialist care provided by stroke units.

Summary Background Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. Methods In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5–10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. Findings 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7–38·4]) than in the placebo group (24·3 points [19·9–28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [ vs 0). Interpretation In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit. Funding Public French National Programme for Clinical Research.

Background: Cognitive dysfunctioning (CDF) is an important issue in stroke, interfering with recovery and social dysfunctioning. We aimed to investigate the clinical and imaging correlates of CDF in patients with a first-ever subacute ischemic stroke and no dementia. Methods: We evaluated CDF 15 days after stroke in a prospective cohort of consecutive patients with a Mini Mental State Examination score ≧23 using a comprehensive neuropsychological battery. CDF was ranked into 3 categories according to Z scores calculated for each test and adjusted for age and education. CDF was analyzed in relation to stroke features. Imaging was assessed using MRI. An ordinal regression procedure was used to determine the clinical correlates of CDF and to compute probabilities. Results: Cognitive evaluation was achieved in 177 consecutive patients (age 50.0 ± 16.0 years). In bivariate analysis, CDF was associated with age, low level of education, depression, neurological deficit at day 15, stroke subtype, arterial territory and leukoaraiosis but not with stroke volume or location. The predictors of CDF were NIHSS score at day 15 (OR = 1.35; 95% CI = 1.05–1.73), middle cerebral artery infarct (OR = 2.96; 95% CI = 1.30–6.73), depression interacting with left stroke side (OR = 1.09; 95% CI = 1.03–1.15), and female gender interacting with high level of education (OR = 0.209; 95% CI = 0.085–0.514). Conclusions: Stroke features correlate with CDF in nondemented patients. These simple criteria may help to predict CDF at bedside in the subacute phase after stroke and to recommend a neuropsychological evaluation for patients’ management. Modeling CDF soon after stroke using simple neurological criteria may be a useful tool for designing clinical trials.

Background and Purpose— Determining cognitive dysfunctioning (CDF) after stroke is an important issue because it influences choices for management in terms of return to previous activities. Because previous research in subacute stroke has shown important variations in CDF rates, we aimed to describe the frequency and neuropsychological profile of CDF in subacute stroke outside dementia. We used a large battery of tests to screen any potentially hidden CDF. Methods— Patients with Mini-Mental State Examination scores ≥23 were prospectively and consecutively included 2 weeks after a first-ever ischemic brain infarct. Stroke features were based on MRI. Four domains were evaluated: instrumental and executive functions, episodic memory, and working memory (WM). Patients were scored using means and compared with education- and age-matched control subjects. Then we attributed Z-scores for each test and each domain. The most relevant cognitive tests characterizing CDF were determined using logistic regression. Results— Among 177 patients (mean age, 50.6 years), 91.5% failed in at least one cognitive domain. WM was the most impaired domain (87.6%) with executive functions (64.4%), episodic memory (64.4%), and instrumental functions (24.9%) being relatively preserved. CDF was associated with age, education, depression, neurological deficit, and leukoaraiosis in bivariate analysis. Using logistic regression, WM tests and age predicted CDF (Modified Paced Auditorial Serial Addition Test: OR=0.96 CI=0.93 to 0.98; Owen-spatial-WM: OR=1.07 CI=1.02 to 1.12; age: OR=0.96 CI=0.93 to 0.98). Conclusion— CDF appears to be almost constant, although underestimated, in subacute stroke. WM could reflect some hidden dysfunctioning, which may interfere with rehabilitation and return to work. Clinical routine may include WM tests in young patients with mild stroke.

International audience; BACKGROUND AND AIMS: Social functioning is impaired in approximately two-thirds of stroke patients of vocational age, even several months after a first ever mild to moderate stroke. The known predictors of social functioning are initial stroke severity, anxiety and depression, and the Mini-Mental State Evaluation, suggesting that cognitive deficits contribute to post-stroke social dysfunctioning. The aim of this study was to evaluate whether cognitive domains correlated with social functioning and to determine the cognitive predictors of social dysfunctioning. METHODS: 74 patients were prospectively included 6 months after a first ever stroke. National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale, depression and anxiety were recorded. Social functioning was recorded using the Work and Social Adjustment Scale (WSAS). An extensive neuropsychological test battery explored general cognitive functioning, episodic memory, instrumental functions, executive functions and working memory. Univariate comparisons assessed the relationships between the neuropsychological tests and scores on the WSAS. Predicting factors for WSAS were determined using ordinal logistic regression. RESULTS: 52 patients (70%; 95% confidence interval 58% to 80%) complained of significant perturbations in work and social functioning. In univariate comparisons, general cognitive functioning, memory, instrumental functions, executive functions and working memory significantly correlated with social functioning. Working memory was the most affected domain. With multivariate modelling, the NIHSS at admission, Hospital Anxiety Depression scale and Owen's Spatial Working Memory test were independent predictors of WSAS. CONCLUSIONS: All cognitive domains were associated with social functioning, working memory being the main cognitive determinant. Our results suggest that cognitive impairment impacts on social dysfunctioning, which is known to be a component of quality of life.

International audience; BACKGROUND: With improvements in stroke treatments, the number of patients with dramatic recovery is increasing. However, many of them are still complaining of difficulties in returning to work and every day activities. The aim was to assess work and social dysfunctioning in patients with minor to moderate stroke and explore its contributing factors. METHODS: Consecutive patients were prospectively included at a median 7 months after a first-ever stroke. Scores on the Work and Social Adjustment Scale (WSAS), a generic self-reported scale for assessing social functioning, were correlated with scores on the National Institutes of Health Stroke Scale (NIHSS), activities of daily living, Hospital Anxiety and Depression scale (HAD) and MMSE, Iowa Scale of Personality Changes and return to work at 1 year. RESULTS: Among the 84 included patients (mean age 43.5 years), 57 (68%; 95% CI 57 to 78%) complained of significant perturbation of functioning attributed to stroke. WSAS was highly significantly related to modified Rankin scale, daily living activities, Iowa Scale of Personality Changes and return to work at 1 year. Using ordinal logistic regression, the contributors to WSAS were initial neurological severity (NIHSS at admission), HAD and MMSE. CONCLUSIONS: The study showed that up to 68% of our patients complained of significant work and social dysfunction due to stroke, despite a good clinical outcome. This self-estimation was correlated to external validation criteria, stressing the high burden of stroke from the patient's viewpoint. Moreover, when compared across diseases, social dysfunctioning after mild stroke was as important as in other major disabling diseases.

Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after stroke. To deliver these cells, an IV injection appears safer than a local graft. We aimed to assess the whole-body biodistribution of IV-injected 99mTc-HMPAO-labeled hMSC in normal rats ( n = 9) and following a right middle cerebral artery occlusion (MCAo, n = 9). Whole-body nuclear imaging, isolated organ counting (at 2 and 20 h after injection) and histology were performed. A higher activity was observed in the right damaged hemisphere of the MCAo group [6.5 ± 0.9 × 10−3 % of injected dose (ID)/g] than in the control group (3.6 ± 1.2 × 10−3 %ID/g), 20 h after injection. In MCAo rats, right hemisphere activity was higher than that observed in the contralateral hemisphere at 2 h after injection (11.6 ± 2.8 vs. 9.8 ± 1.7 × 10−3 %ID/g). Following an initial hMSC lung accumulation, there was a decrease in pulmonary activity from 2 to 20 h after injection in both groups. The spleen was the only organ in which activity increased between 2 and 20 h. The presence of hMSC was documented in the spleen, liver, lung, and brain following histology. IV-injected hMSC are transiently trapped in the lungs, can be sequestered in the spleen, and are predominantly eliminated by kidneys. After 20 h, more hMSC are found in the ischemic lesion than into the undamaged cerebral tissue. IV delivery of hMSC could be the initial route for a clinical trial of tolerance.

We report two patients aged 65 and 61 years, who presented a subacute dementia with normal CT scan without contrast injection. Angiography showed a dural arteriovenous malformation. The patients improved dramatically with treatment of the malformation. Dementia was characterised by frontal dysfunction, emotional disorders, mnesic and praxic impairment. This neuropsychological pattern suggests a profile of global dementia in the field of vascular dementia.

The purpose of the present study was to evaluate in vivo the effect of a non competitive antagonist of the NMDA receptor, eliprodil, on the size of a focal ischaemic insult and on its temporal evolution in a rat model, using a spin-echo diffusion magnetic resonance imaging multislice technique. Rats were either injected with 1 mg/kg i.v. of eliprodil or with the vehicle only (placebo) 5 min after middle cerebral artery occlusion, or not injected (controls). Ten coronal slices were acquired every hour, up to 7 h after occlusion of the artery, and the volume of hyperintense signals was measured at each time point and for each animal. Diffusion magnetic resonance images revealed that the administration of eliprodil reduced significantly (by 50% or more) the volume of ischaemia, up to 7 h after occlusion, particularly in the cortex of the ipsilateral hemisphere. The results show the potential efficacy of eliprodil to reduce the cerebral ischaemic volume after arterial occlusion, thus confirming the interest of glutamate receptor antagonists in the treatment of ischaemia.

Background and Purpose We carried out a door-to-door survey on stroke prevalence at high altitude in Cuzco City, a town in the Peruvian Andes located 3380 m above sea level. Methods and Results Among the 3246 screened individuals over 15 years old, there were 21 cases of first-ever completed stroke, yielding a crude prevalence ratio of 6.47 per 1000 (95% confidence interval [CI], 3.71 to 8.93 per 1000). The age-adjusted to WHO population point prevalence ratio was 5.74 per 1000 (95% CI, 3.14 to 8.35 per 1000), and the age-adjusted to North American US population point prevalence ratio was 8.58 per 1000 (95% CI, 5.44 to 11.75 per 1000). Multivariate logistic regression analysis suggested that age, polycythemia, high consumption of alcohol, and area of residence were associated with stroke prevalence. Our results suggest that the stroke prevalence in the central areas of Cuzco with sedentary people having a relatively high standard of living was higher than that in the peripheral areas with people with a relatively lower standard of living and less sedentary activities (odds ratio, 5.8; 95% CI, 1.4 to 23). Conclusions The prevalence of stroke suggests that stroke may be a public health problem in developing countries. This study suggests the importance of environmental factors such as altitude and lifestyle in stroke occurrence. The role of these factors should be confirmed and taken into account in future stroke prevalence studies.

Cerebrovascular disease accounts for a substantial worldwide burden of death and disability. In addition to well-established risk factors such as hypertension, myocardial infarction, diabetes mellitus, and smoking,1 an increasing body of evidence suggests that lifestyle factors contribute to the risk of stroke. In this issue of the Journal, Berger et al.2 report, on the basis of their study of U.S. male physicians 40 to 84 years of age who were participants in the Physicians' Health Study, that light-to-moderate alcohol consumption may prevent stroke. The overall relative risk of stroke was 0.79 (95 percent confidence interval, 0.66 to 0.94) for those . . .

Cerebral venous sinus thrombosis is rare and can be promoted by various conditions. We report the case of cerebral venous thrombosis in a patient using androgens. A 31-year-old man using androgens for bodybuilding was admitted for headache and vomiting. He had cerebral venous sinus thrombosis, but extensive examinations did not reveal any known cause. We suggest that androgens may promote cerebral venous thrombosis. The mechanisms of venous thrombosis related to androgens may be platelet activation or an increase in coagulation factors. Because androgen use may be frequent and hidden in athletes, it may be an underestimated cause of cerebral venous sinus thrombosis in the young.