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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 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.

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.

Automatic segmentation of chronic stroke lesion from magnetic resonance images (MRI) is motivated by the increasing need for reproducible and repeatable endpoints in clinical trials. The task is non-trivial, due to a number of confounding factors, including heterogeneous lesion intensity, irregular shape, and large deformations that render the conventional use of prior probabilistic atlases challenging. In this paper, we introduce a hidden Markov random field model that avails of a novel prior probabilistic vascular territory atlas to describe the natural vascular constraints in the brain. The vascular territory atlas is deformed in a joint registration-segmentation framework to overcome subject-specific morphological variability. T1-w and Flair sequences are used to populate our model, and a variational approach is implemented to find a solution. The performance of our model is demonstrated on two datasets, and compared to manual delineations by expert raters.

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.

Diffusion Tensor Imaging (DTI), the Fractional Anisotropy (FA) is used to measure the integrity of the white matter (WM); it is considered as a biomarker for stroke recovery. This measure is highly sensitive to applied pre-processing steps; in particular, the presence of a lesion may result into severe misregistration. In this paper, it is proposed to quantitatively assess the impact of large stroke lesions onto the registration process. To reduce this impact, a new registration algorithm, that localizes the lesion via Bayesian estimation, is proposed.

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.

Pain, in its various manifestations, is our most distressing human experience. A large volume of evidence extending from psychology to neuroimaging emphasizes the powerful influence of both social and physical pain on mammalian well-being and survival.1 Although pain is defined as an unpleasant sensation caused by nociceptive stimuli,2 the concept encompasses social as well as physical pain. Painful emotional feelings are associated with the loss of social connection owing to rejection, exclusion from a group, personal failure, or the death of a loved one. We often describe the experience of social pain by using terms for physical pain,1 making reference . . .

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.

Stroke is the second leading cause of death worldwide and the most common cause of severe disability. Neuroprotection and repair mechanisms supporting endogenous brain plasticity are often insufficient to allow complete recovery. While numerous neuroprotective drugs trials have failed to demonstrate benefits for patients, they have provided interesting translational research lessons related to neurorestorative therapy mechanisms in stroke. Stroke damage is not limited to neurons but involve all brain cell type including the extracellular matrix in a "glio-neurovascular niche". Targeting a range of host brain cells, biotherapies such as growth factors and therapeutic cells, currently hold great promise as a regenerative medical strategy for stroke. These techniques can promote both neuroprotection and delayed neural repair through neuro-synaptogenesis, angiogenesis, oligodendrogliogenesis, axonal sprouting and immunomodulatory effects. Their complex mechanisms of action are interdependent and vary according to the particular growth factor or grafted cell type. For example, while "peripheral" stem or stromal cells can provide paracrine trophic support, neural stem/progenitor cells (NSC) or mature neurons can act as more direct neural replacements. With a wide therapeutic time window after stroke, biotherapies could be used to treat many patients. However, guidelines for selecting the optimal time window, and the best delivery routes and doses are still debated and the answers may depend on the chosen product and its expected mechanism including early neuroprotection, delayed neural repair, trophic systemic transient effects or graft survival and integration. Currently, the great variety of growth factors, cell sources and cell therapy products form a therapeutic arsenal that is available for stroke treatment. Their effective clinical use will require prior careful considerations regarding safety (e.g. tumorgenicity, immunogenicity), potential efficacy, cell characterization, delivery route and in vivo biodistribution. Bone marrow-derived cell populations such as mesenchymal stromal/stem cells (MSC) or mononuclear cells (MNC), umbilical cord stem cells and NSC are most investigated notably in clinical trials. Finally, we discuss perspectives concerning potential novel biotherapies such as combinatorial approaches (growth factor combined with cell therapy, in vitro optimization of cell products, or co-transplantation) and the development of biomaterials, which could be used as injectable hydrogel scaffold matrices that could protect a cell graft or selectively deliver drugs and growth factors into the post-stroke cavity at chronic stages. Considering the remaining questions about the best procedure and the safety cautions, we can hope that future translational research about biotherapies will bring more efficient treatments that will decrease post-stroke disability for many patients.

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.

Background and Purpose —Hemorrhagic transformation (HT) is the most critical complication of thrombolytics in clinical trials in acute stroke. The aim of this study was to determine the rates and the predictors of HT in the Multicenter Acute Stroke Trial–Europe (MAST-E) study. Methods —We performed a post hoc analysis of MAST-E data designed to assess the safety and efficacy of streptokinase administered intravenously within 6 hours of stroke onset. HT included all intracerebral hemorrhages and symptomatic hemorrhages (SHT) associated with clinical worsening. The predictors of HT and SHT were determined using multivariate modeling. Results —Among the 310 patients included, 159 patients had HT and 37 SHT (97 and 33 in the streptokinase group and 62 and 4 in the placebo group, respectively). Patients with SHT had significantly more atrial fibrillation, diabetes mellitus, no heparin use, streptokinase treatment, and early CT signs. In the multivariate analysis, HT was predicted by early CT signs and streptokinase treatment. SHT was predicted by diabetes mellitus, early CT signs, streptokinase treatment, and the interaction between streptokinase treatment and decreased level of consciousness. Among the streptokinase-treated patients, the same predictors remained. Conclusions —The relative risks of HT after streptokinase were in the same range in MAST-E as in other streptokinase and tPA trials. Early CT signs were strong predictors of both HT and SHT, stressing that these patients are at high risk of bleeding. In our study, the predictors of HT and SHT were similar to those of tPA trials in acute stroke.

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.

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.

In clinical trials, assessing efficacy is based on validated scales, and the primary endpoint is usually based on a single scale. The aim of the review is to revisit the concepts and methods to design and analyze studies focused on restoration, recovery and or compensation. These studies are becoming more frequent with the development of restorative medicine. After discussing the definitions of recovery, we address the concept of recovery as the regain of lost capabilities, when the patient reaches a new equilibrium. Recovery is a dynamic process which assessment includes information from initial and final status, their difference, the difference between the final status of the patient and normality, and the speed of restoration. Finally, recovery can be assessed either for a specific function (focal restoration) or for a more global restoration. A single scale is not able to assess all the facets of a skill or a function, therefore complementary information should be collected and analyzed simultaneously to be tested in a single analysis. We are suggesting that recovery should be considered as a latent variable and therefore cannot be measured in pure form. We are also suggesting to customize the data collection and analysis according to the characteristics of the subjects, the mechanisms of action and consequences of the intervention. Moreover, recovery trials should benefit from latent variable analysis methods. Structural equation modeling is likely the best candidate for this approach applicable in pre-clinical and clinical studies.