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1. Regenerative stem cell therapy for stroke in Europe (RESSTORE): a multicenter randomized controlled efficacy clinical trial

Author

Loïc Legris, Anaick Moisan, Assia Jaillard, Louise Bonnet, Thierry Moulin, Igor Sibon, Emmanuel Touzé, Isabelle Favre-Wiki, Charlotte Cordonnier, Lucie Dellaschiava, Mikael Mazighi, Charlotte Rosso, Sonia Alamowitch, David Calvet, Marianne Barbieux-Guillot, Stephan Roux, Alain-Ali Mojallal, Fabien Boucher, Antoine Thuriot, Julie Soulard, Bernadette Naegele, Dominic Perennou, Matthieu Roustit, Zaza Putkaradze, Marc Hommel, Audrey Lehmann, Julien Colombat, Fatima Chorfa, Delphine Maucort-Boulch, Laurent Lamalle, Sylvie Grand, Alexandre Krainik, and Olivier Detante

Subjects
stroke, cell therapy, stem cells, ADSC, regeneration, recovery, Medicine
Abstract

IntroductionEncouraging the activation of brain repair mechanisms and fostering spontaneous functional recovery in stroke patients hold great promise for alleviating the global burden of this condition and allowing an extended therapeutic time window. Cell-based regenerative therapy (with mesenchymal stem/stromal cells, such as adipose-derived stem cells [ADSCs]) is particularly attractive considering its excellent safety profile, low immunogenicity after allogeneic application, and well-established functional benefits on stroke recovery in animal models. This study aims to assess the efficacy and safety effects of intravenous (IV) infusion of freshly cultured allogeneic ADSCs on recovery after ischemic stroke.Population and methodsRESSTORE is a multicentric, randomized 1:1 controlled double-blind clinical trial. Eighty patients will be enrolled in nine French stroke centers. The main inclusion criteria are ≥18 years of age, acute hemispheric ischemic stroke, and a National Institutes of Health Stroke Scale (NIHSS) score of ≥7, including a motor subscore of ≥3. According to the previous dose-escalation safety trial data, the maximum tolerated dose of 3 million ADSCs/kg was selected. IV infusion was performed within 10 days following stroke onset, with a follow-up over 2 years.OutcomesThe primary endpoint is the motor NIHSS subscore, computed as the sum of the upper limb, lower limb, and hand scores, measured 6 months after stroke onset to assess motor recovery. The secondary outcomes are the occurrence of death/serious adverse events, clinical scores (the detailed NIHSS scores, Montreal Cognitive Assessment scores, modified Rankin Scale scores, Aphasia Handicap Scores, Depression Intensity Scale Circles scores, Fatigue Scale scores, etc.), immune monitoring (for the first 30 patients), and multimodal biomarkers derived from diffusion and functional magnetic resonance imaging.DiscussionThis study may provide some evidence for the effects of freshly cultured allogenic ADSCs IV infusion in subacute stroke that may help design a larger international randomized controlled trial.

Published
2024
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2. Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype

Author

Bérengère Koehl, Cédric Vrignaud, Mahmoud Mikdar, Thankam S Nair, Lucy Yang, Seyve Landry, Guy Laiguillon, Claudine Giroux‐Lathuile, Sophie Anselme‐Martin, Hanane El Kenz, Olivier Hermine, Narla Mohandas, Jean Pierre Cartron, Yves Colin, Olivier Detante, Raphaël Marlu, Caroline Le Van Kim, Thomas E Carey, Slim Azouzi, and Thierry Peyrard

Subjects
blood group antigen, hearing impairment, red blood cells, SLC44A2, transfusion, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Blood phenotypes are defined by the presence or absence of specific blood group antigens at the red blood cell (RBC) surface, due to genetic polymorphisms among individuals. The recent development of genomic and proteomic approaches enabled the characterization of several enigmatic antigens. The choline transporter‐like protein CTL2 encoded by the SLC44A2 gene plays an important role in platelet aggregation and neutrophil activation. By investigating alloantibodies to a high‐prevalence antigen of unknown specificity, found in patients with a rare blood type, we showed that SLC44A2 is also expressed in RBCs and carries a new blood group system. Furthermore, we identified three siblings homozygous for a large deletion in SLC44A2, resulting in complete SLC44A2 deficiency. Interestingly, the first‐ever reported SLC44A2‐deficient individuals suffer from progressive hearing impairment, recurrent arterial aneurysms, and epilepsy. Furthermore, SLC44A2null individuals showed no significant platelet aggregation changes and do not suffer from any apparent hematological disorders. Overall, our findings confirm the function of SLC44A2 in hearing preservation and provide new insights into the possible role of this protein in maintaining cerebrovascular homeostasis.

Published
2023
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3. Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats

Author

Mari Carmen Gómez-de Frutos, Fernando Laso-García, Luke Diekhorst, Laura Otero-Ortega, Blanca Fuentes, Jukka Jolkkonen, Olivier Detante, Anaick Moisan, Arturo Martínez-Arroyo, Exuperio Díez-Tejedor, María Gutiérrez-Fernández, and on behalf of RESSTORE consortium

Subjects
Adipose tissue, Behavioral outcome, Brain repair, Experimental model, Hyperglycemia, Mesenchymal stem cells, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract

Abstract Background Over 50% of acute stroke patients have hyperglycemia, which is associated with a poorer prognosis and outcome. Our aim was to investigate the impact of hyperglycemia on behavioral recovery and brain repair of delivered human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) in a rat model of permanent middle cerebral artery occlusion (pMCAO). Methods Hyperglycemia was induced in rats by the administration of nicotinamide and streptozotocin. The rats were then subjected to stroke by a pMCAO model. At 48 h post-stroke, 1 × 106 hAD-MSCs or saline were intravenously administered. We evaluated behavioral outcome, infarct size by MRI, and brain plasticity markers by immunohistochemistry (glial fibrillary acidic protein [GFAP], Iba-1, synaptophysin, doublecortin, CD-31, collagen-IV, and α-smooth muscle actin [α-SMA]). Results The hyperglycemic group exhibited more severe neurological deficits; lesion size and diffusion coefficient were larger compared with the non-hyperglycemic rats. GFAP, Iba-1, and α-SMA were increased in the hyperglycemic group. The hyperglycemic rats administered hAD-MSCs at 48 h after pMCAO had improved neurological impairment. Although T2-MRI did not show differences in lesion size between groups, the rADC values were lower in the treated group. Finally, the levels of GFAP, Iba-1, and arterial wall thickness were lower in the treated hyperglycemic group than in the nontreated hyperglycemic group at 6 weeks post-stroke. Conclusions Our data suggest that rats with hyperglycemic ischemic stroke exhibit increased lesion size and impaired brain repair processes, which lead to impairments in behavioral recovery after pMCAO. More importantly, hAD-MSC administration induced better anatomical tissue preservation, associated with a good behavioral outcome.

Published
2019
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4. Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke

Author

Firdaus Fabrice Hannanu, Thomas A. Zeffiro, Laurent Lamalle, Olivier Heck, Félix Renard, Antoine Thuriot, Alexandre Krainik, Marc Hommel, Olivier Detante, Assia Jaillard, K. Garambois, M. Barbieux-Guillot, I. Favre-Wiki, S. Grand, J.F. Le Bas, A. Moisan, M.J. Richard, F. De Fraipont, J. Gere, S. Marcel, W. Vadot, G. Rodier, D. Perennou, A. Chrispin, P. Davoine, B. Naegele, P. Antoine, I. Tropres, and F. Renard

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

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

Published
2017
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5. Evaluation of Parametric Response Mapping to Assess Therapeutic Response to Human Mesenchymal Stem Cells after Experimental Stroke

Author

Rui He, Anaïck Moisan, Olivier Detante, Chantal Rémy, Alexandre Krainik, Emmanuel Luc Barbier, and Benjamin Lemasson

Subjects
Medicine
Abstract

Stroke is the leading cause of disability in adults. After the very narrow time frame during which treatment by thrombolysis and mechanical thrombectomy is possible, cell therapy has huge potential for enhancing stroke recovery. Accurate analysis of the response to new therapy using imaging biomarkers is needed to assess therapeutic efficacy. The aim of this study was to compare 2 analysis techniques: the parametric response map (PRM), a voxel-based technique, and the standard whole-lesion approach. These 2 analyses were performed on data collected at 4 time points in a transient middle cerebral artery occlusion (MCAo) model, which was treated with human mesenchymal stem cells (hMSCs). The apparent diffusion coefficient (ADC), cerebral blood volume (CBV), and vessel size index (VSI) were mapped using magnetic resonance imaging (MRI). Two groups of rats received an intravenous injection of either 1 mL phosphate-buffered saline (PBS)-glutamine (MCAo-PBS, n = 10) or 3 million hMSCs (MCAo-hMSC, n = 10). One sham group was given PBS-glutamine (sham, n = 12). Each MRI parameter was analyzed by both the PRM and the whole-lesion approach. At day 9, 1 d after grafting, PRM revealed that hMSCs had reduced the fraction of decreased ADC (PRM ADC − : MCAo-PBS 6.7% ± 1.7% vs. MCAo-hMSC 3.3% ± 2.4%), abolished the fraction of increased CBV (PRM CBV+ : MCAo-PBS 16.1% ± 3.7% vs. MCAo-hMSC 6.4% ± 2.6%), and delayed the fraction of increased VSI (PRM VSI+ : MCAo-PBS 17.5% ± 6.3% vs. MCAo-hMSC 5.4% ± 2.6%). The whole-lesion approach was, however, insensitive to these early modifications. PRM thus appears to be a promising technique for the detection of early brain changes following treatments such as cell therapy.

Published
2017
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6. Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect

Author

Anaïck Moisan, Isabelle Favre, Claire Rome, Florence De Fraipont, Emmanuelle Grillon, Nicolas Coquery, Hervé Mathieu, Virginie Mayan, Bernadette Naegele, Marc Hommel, Marie-Jeanne Richard, Emmanuel Luc Barbier, Chantal Remy, and Olivier Detante

Subjects
Medicine
Abstract

Stroke is the leading cause of disability in adults. Many current clinical trials use intravenous (IV) administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs). This autologous graft requires a delay for ex vivo expansion of cells. We followed microvascular effects and mechanisms of action involved after an IV injection of human BM-MSCs (hBM-MSCs) at a subacute phase of stroke. Rats underwent a transient middle cerebral artery occlusion (MCAo) or a surgery without occlusion (sham) at day 0 (D0). At D8, rats received an IV injection of 3 million hBM-MSCs or PBS-glutamine. In a longitudinal behavioral follow-up, we showed delayed somatosensory and cognitive benefits 4 to 7 weeks after hBM-MSC injection. In a separate longitudinal in vivo magnetic resonance imaging (MRI) study, we observed an enhanced vascular density in the ischemic area 2 and 3 weeks after hBM-MSC injection. Histology and quantitative polymerase chain reaction (qPCR) revealed an overexpression of angiogenic factors such as Ang1 and transforming growth factor-β1 (TGF-β1) at D16 in hBM-MSC-treated MCAo rats compared to PBS-treated MCAo rats. Altogether, delayed IV injection of hBM-MSCs provides functional benefits and increases cerebral angiogenesis in the stroke lesion via a release of endogenous angiogenic factors enhancing the stabilization of newborn vessels. Enhanced angiogenesis could therefore be a means of improving functional recovery after stroke.

Published
2016
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7. Biomaterial Applications in Cell-Based Therapy in Experimental Stroke

Author

Ligia S. B. Boisserand, Tomonobu Kodama, Jérémie Papassin, Rachel Auzely, Anaïck Moisan, Claire Rome, and Olivier Detante

Subjects
Internal medicine, RC31-1245
Abstract

Stroke is an important health issue corresponding to the second cause of mortality and first cause of severe disability with no effective treatments after the first hours of onset. Regenerative approaches such as cell therapy provide an increase in endogenous brain structural plasticity but they are not enough to promote a complete recovery. Tissue engineering has recently aroused a major interesting development of biomaterials for use into the central nervous system. Many biomaterials have been engineered based on natural compounds, synthetic compounds, or a mix of both with the aim of providing polymers with specific properties. The mechanical properties of biomaterials can be exquisitely regulated forming polymers with different stiffness, modifiable physical state that polymerizes in situ, or small particles encapsulating cells or growth factors. The choice of biomaterial compounds should be adapted for the different applications, structure target, and delay of administration. Biocompatibilities with embedded cells and with the host tissue and biodegradation rate must be considerate. In this paper, we review the different applications of biomaterials combined with cell therapy in ischemic stroke and we explore specific features such as choice of biomaterial compounds and physical and mechanical properties concerning the recent studies in experimental stroke.

Published
2016
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8. Intravenous Administration of Tc-HMPAO-Labeled Human Mesenchymal Stem Cells after Stroke: In Vivo Imaging and Biodistribution

Author

Olivier Detante, Anaïck Moisan, Julien Dimastromatteo, Marie-Jeanne Richard, Laurent Riou, Emmanuelle Grillon, Emmanuel Barbier, Marie-Dominique Desruet, Florence De Fraipont, Christoph Segebarth, Assia Jaillard, Marc Hommel, Catherine Ghezzi, and Chantal Remy

Subjects
Medicine
Abstract

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 99m Tc-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.

Published
2009
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9. Endovascular Therapy or Medical Management Alone for Isolated Posterior Cerebral Artery Occlusion: A Multicenter Study

Author

Candice Sabben, Frédérique Charbonneau, François Delvoye, Davide Strambo, Mirjam R. Heldner, Elodie Ong, Adrien Ter Schiphorst, Hilde Henon, Wagih Ben Hassen, Thomas Agasse-Lafont, Loïc Legris, Igor Sibon, Valérie Wolff, Denis Sablot, Mahmoud Elhorany, Cécile Preterre, Nour Nehme, Sébastien Soize, David Weisenburger-Lile, Aude Triquenot-Bagan, Gioia Mione, Andreea Aignatoaie, Jérémie Papassin, Roxana Poll, Yannick Béjot, Emmanuel Carrera, Pierre Garnier, Patrik Michel, Guillaume Saliou, Pasquale Mordasini, Yves Berthezene, Vincent Costalat, Nicolas Bricout, Gregory W. Albers, Mikael Mazighi, Guillaume Turc, Pierre Seners, Kateryna Antonenko, Caroline Arquizan, Lynda Benammar, Claire Boutet, Frédéric Clarençon, Pierre-Olivier Comby, Hubert Desal, Olivier Detante, François Eugene, Emmanuel Gerardin, Benjamin Gory, Stéphane Kremer, Sylvain Ledure, Mathieu Krug, Bertrand Lapergue, Philippe Niclot, Christophe Magni, Michael Obadia, Canan Ozsancak, Fernando Pico, Sara Pilgram-Pastor, Raoul Pop, Sébastien Richard, Charlotte Rosso, Julien Savatovsky, Solène Moulin, Clément Tracol, and Martin Zbinden

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Background: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown. Methods: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0–2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0–1), symptomatic intracranial hemorrhage, and early neurological deterioration. Results: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63–82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4–10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66–1.01]; P =0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95–1.43]; P =0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35–4.67]; P =0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64–3.84]; P Conclusions: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Published
2023
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11. A novel injectable radiopaque hydrogel with potent properties for multicolor CT imaging in the context of brain and cartilage regenerative therapy

Author

Moustoifa Said, Clément Tavakoli, Chloé Dumot, Karine Toupet, Yuxi Clara Dong, Nora Collomb, Céline Auxenfans, Anaïck Moisan, Bertrand Favier, Benoit Chovelon, Emmanuel Luc Barbier, Christian Jorgensen, David Peter Cormode, Danièle Noël, Emmanuel Brun, Hélène Elleaume, Marlène Wiart, Olivier Detante, Claire Rome, and Rachel Auzély-Velty

Subjects
Article
Abstract

Cell therapy is promising to treat many conditions, including neurological and osteoarticular diseases. Encapsulation of cells within hydrogels facilitates cell delivery and can improve therapeutic effects. However, much work remains to be done to align treatment strategies with specific diseases. The development of imaging tools that enable monitoring cells and hydrogel independently is key to achieving this goal. Our objective herein is to longitudinally study an iodine-labeled hydrogel, incorporating gold-labeled stem cells, by bicolor CT imaging afterin vivoinjection in rodent brains or knees. To this aim, an injectable self-healing hyaluronic acid (HA) hydrogel with long-persistent radiopacity was formed by the covalent grafting of a clinical contrast agent on HA. The labeling conditions were tuned to achieve sufficient X-ray signal and to maintain the mechanical and self-healing properties as well as injectability of the original HA scaffold. The efficient delivery of both cells and hydrogel at the targeted sites was demonstrated by synchrotron K-edge subtraction-CT. The iodine labeling enabled to monitor the hydrogel biodistributionin vivoup to 3 days post-administration, which represents a technological first in the field of molecular CT imaging agents. This tool may foster the translation of combined cell-hydrogel therapies into the clinics.

Published
2023

12. White matter tract disruption is associated with ipsilateral hand impairment in subacute stroke: a diffusion MRI study

Author

Firdaus Fabrice Hannanu, Bernadette Naegele, Marc Hommel, Alexandre Krainik, Olivier Detante, and Assia Jaillard

Subjects
Adult, Male, Hand Strength, Pyramidal Tracts, Middle Aged, White Matter, Stroke, Cross-Sectional Studies, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Anisotropy, Humans, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

The ipsilateral hand (ILH) is impaired after unilateral stroke, but the underlying mechanisms remain unresolved. Based on the degeneracy theory of network connectivity that many connectivity patterns are functionally equivalent, we hypothesized that ILH impairment would result from the summation of microstructural white matter (WM) disruption in the motor network, with a task-related profile. We aimed to determine the WM disruption patterns associated with ILH impairment.This was a cross-sectional analysis of patients in the ISIS-HERMES Study with ILH and diffusion-MRI data collected 1 month post-stroke. Patients performed three tasks, the Purdue Pegboard Test (PPT), handgrip strength, and movement time. Fractional anisotropy (FA) derived from diffusion MRI was measured in 33 WM regions. We used linear regression models controlling for age, sex, and education to determine WM regions associated with ILH impairment.PPT was impaired in 42%, grip in 59%, and movement time in 24% of 29 included patients (mean age, 51.9 ± 10.5 years; 21 men). PPT was predicted by ipsilesional corticospinal tract (i-CST) (B = 17.95; p = 0.002) and superior longitudinal Fasciculus (i-SLF) (B = 20.52; p = 0.008); handgrip by i-CST (B = 109.58; p = 0.016) and contralesional anterior corona radiata (B = 42.69; p = 0.039); and movement time by the corpus callosum (B = - 1810.03; p = 0.003) i-SLF (B = - 917.45; p = 0.015), contralesional pons-CST (B = 1744.31; p = 0.016), and i-corticoreticulospinal pathway (B = - 380.54; p = 0.037).ILH impairment was associated with WM disruption to a combination of ipsilateral and contralesional tracts with a pattern influenced by task-related processes, supporting the degeneracy theory. We propose to integrate ILH assessment in rehabilitation programs and treatment interventions such as neuromodulation.

Published
2022
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13. Ipsilateral hand impairment predicts long‐term outcome in patients with subacute stroke

Author

Rien Anggraini Razak, Firdaus Fabrice Hannanu, Bernadette Naegele, Marc J. G. Hommel, Olivier Detante, and Assia Jaillard

Subjects
Stroke, Disability Evaluation, Treatment Outcome, Hand Strength, Neurology, Stroke Rehabilitation, Humans, Longitudinal Studies, Neurology (clinical), Hand
Abstract

Ipsilateral hand (ILH) impairment is documented following motor stroke, but its impact on long-term outcome remains unknown. We assessed ILH impairment in subacute stroke and tested whether ILH impairment predicted long-term outcome.We performed a longitudinal study in 209 consecutive patients with unilateral stroke and sensorimotor deficit at admission. ILH impairment was evaluated using the Purdue Pegboard Test (PPT) and handgrip strength and defined as mild (z-score -1) or moderate (z-score -1.65). We used logistic regression (LR) to predict outcome assessed 9 (range, 7-12) months post-stroke with the modified Rankin scale (mRS) categorized into good (mRS ≤ 1) and poor outcome (mRS ≥ 2). For internal validation, LR-bootstrapping and cross-validation with LASSO and Random Forest were performed.ILH impairment assessed at 89.04 ± 45.82 days post-stroke was moderate in 10.53% (95% CI 6.7, 14.83) for PPT and 17.22% (95% CI 11.96, 22.49) for grip, and mild in 21.05% (95% CI 15.78, 26.79) for PPT and 35.89 (95% CI 29.67, 42.58) for grip. Good outcome was predicted by ILH-PPT (B = 1.03 [95% CI 0.39, 3.31]), ILH-grip (B = 1.16 [95% CI 0.54, 3.53]), low NIHSS-discharge (B = -1.57 [95% CI -4.0, -1.19]), and no depression (B = -0.62 [95% CI -1.63, -0.43]), accounting for stroke delay (B = -0.011 [95% CI -0.06, 0.01]). Model efficiency was 91.6% (AUC = 0.977; 95% CI 0.959, 0.996). LASSO and Random Forest methods provided similar results, confirming the LR model robustness.ILH impairment is frequent after motor stroke and predicts long-term outcome. We propose to integrate ILH impairment into rehabilitation programs to improve recovery and serve research interventions such as neuromodulation.

Published
2022
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14. Évaluation médico-économique de deux types d'imagerie diagnostique, irm versus scanner chez des patients suspectés d'accident vasculaire cérébral ischémique (avci): etude magritte - une étude prospective, contrôlée, randomisée

Author

Hocine Redjem, Pascal Mosimann, Michel Piotin, Michael Obadia, Julien Svatovsky, Bertrand Lapergue, Stéphanie Condette-Auliac, Emmanuel Touzé, Julien Baud, Olivier Detante, Alexandre Krainik, Sébastien Richard, Benjamin Gory, Jean-Marc Olivot, Christophe Cognard, Jean-Pierre Guichard, Serge Timsit, Ben Salem Douraied, Vincent Costalat, and Mikaël Mazighi

Subjects
Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, Neurology (clinical)
Published
2023
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16. Lack of the human choline transporter-like protein CTL2 causes hearing impairment and a rare red blood cell phenotype

Author

Bérengère Koehl, Cédric Vrignaud, Mahmoud Mikdar, Thankam S. Nair, Lucy Yang, Guy Laiguillon, Sophie Anselme-Martin, Claudine Giroux-Lathuile, Hanane El Kenz, Olivier Hermine, Narla Mohandas, Jean Pierre Cartron, Yves Colin, Olivier Detante, Caroline Le Van Kim, Thomas E. Carey, Slim Azouzi, and Thierry Peyrard

Abstract

Recent genome-wide association and murine studies identified the human neutrophil antigen -3a/b polymorphism (HNA-3a/b) in SLC44A2 (rs2288904-G/A) as a risk factor in venous thromboembolism (VTE). The choline transporter-like protein CTL2 encoded by the SLC44A2 gene plays an important role in platelet aggregation and neutrophil interaction with the von Willebrand factor. By investigating alloantibodies to a high-prevalence antigen of unknown specificity, found in patients with a rare blood type, we showed that CTL2 is also expressed in red blood cells and carries a new blood group system. Furthermore, we identified three siblings of European ancestry who are homozygous for a large deletion in SLC44A2, resulting in complete CTL2 deficiency. Interestingly, the first-ever reported CTL2-deficient individuals suffer from progressive hearing impairment, recurrent arterial aneurysms and epilepsy. In contrast to Slc44a2-/- mice, CTL2null individuals showed normal platelet aggregation and do not suffer from any apparent hematological disorders. In addition, CD34+ cells from CTL2null patients undergo normal ex vivo erythropoiesis, indicating that CTL2 is not essential for erythroid proliferation and differentiation. Overall, our findings confirm the function of CTL2 in hearing preservation and provide new insights into the possible role of this protein in maintaining cerebrovascular homeostasis.

Published
2022
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17. Spatiotemporal patterns of sensorimotor fMRI activity influence hand motor recovery in subacute stroke: A longitudinal task-related fMRI study

Author

Fabrice F. Hannanu, Assia Jaillard, Olivier Detante, Bernadette Naegele, and Issa Goundous

Subjects
medicine.medical_specialty, Movement, Cognitive Neuroscience, Experimental and Cognitive Psychology, Superior parietal lobule, behavioral disciplines and activities, 050105 experimental psychology, Task (project management), 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Neuroplasticity, medicine, Humans, Purdue Pegboard Test, 0501 psychology and cognitive sciences, Stroke, Hand Strength, musculoskeletal, neural, and ocular physiology, 05 social sciences, GRASP, Inferior parietal lobule, Recovery of Function, Hand, medicine.disease, Magnetic Resonance Imaging, body regions, Neuropsychology and Physiological Psychology, Primary motor cortex, Psychology, psychological phenomena and processes, 030217 neurology & neurosurgery
Abstract

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.

Published
2020
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19. Should Patients With Acute Minor Ischemic Stroke With Isolated Internal Carotid Artery Occlusion Be Thrombolysed?

Author

Naouel Boulenoir, Guillaume Turc, Adrien Ter Schiphorst, Mirjam R. Heldner, Davide Strambo, Nadia Laksiri, Isabelle Girard Buttaz, Jérémie Papassin, Igor Sibon, Nicolas Chausson, Patrik Michel, Charlotte Rosso, Frédéric Bourdain, Chantal Lamy, David Weisenburger-Lile, Pierre Agius, Marion Yger, Michael Obadia, Denis Sablot, Nicolas Legris, Simon Jung, Sara Pilgram-Pastor, Hilde Henon, Lucy Bernardaud, Caroline Arquizan, Jean-Claude Baron, Pierre Seners, Wagih Ben Hassen, Bertrand Lapergue, Ludovic Lucas, Didier Leys, Frédéric Philippeau, Omar Bennani, Laura Mechtouff, Frédéric Klapczynski, Olivier Detante, Vincent Costalat, Gioia Mione, Sébastien Gazzola, Séverine Debiais, Serkan Cakmak, Valer Grigoras, Christian Denier, Didier Smadja, François Mounier-Vehier, Roxane Peres, Laurent Spelle, Nicolas Bricout, Serge Bracard, Aude Triquenot, Aïcha Lyoubi, Jean-Philippe Cottier, Duc-Long Duong, Camille Ollivier, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Neurologie [Hôpital Sainte-Anne - APHP] (Paris CB2 2QQ), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GHU Paris Psychiatrie et Neurosciences, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Université de Montpellier (UM), Université de Lausanne = University of Lausanne (UNIL), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Grenoble, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Bordeaux [Bordeaux], Centre Hospitalier Sud Francilien, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurologie - Côte Basque, Centre Hospitalier de la Côte Basque (CHCB), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Hôpital Foch [Suresnes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier de Saint-Nazaire, CHU Saint-Antoine [AP-HP], Infrastructure de recherche clinique en psychiatrie adulte [ICM Paris] (iCRIN psychiatrie), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Saint Jean de Perpignan, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Saint-Anne (GHU Paris), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)

Subjects
Advanced and Specialized Nursing, Carotid Artery Diseases, carotid artery, anticoagulant, 360 Soziale Probleme, Sozialdienste, Anticoagulants, Arterial Occlusive Diseases, Thrombosis, embolism, Brain Ischemia, Stroke, Treatment Outcome, Fibrinolytic Agents, thrombus, internal, Humans, Thrombolytic Therapy, Neurology (clinical), Cardiology and Cardiovascular Medicine, 610 Medizin und Gesundheit, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Carotid Artery, Internal, Ischemic Stroke, Retrospective Studies, Thrombectomy
Abstract

Background: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT—as compared to no-IVT—may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation. Methods: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score 7d ) and 3-month modified Rankin Scale score 0 to 1. Results: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END 7d occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07–3.92]; P =0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P =0.09). However, END 7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END 7d : adjusted hazard ratio, 1.29 [95% CI, 0.75–2.23]; P =0.37; modified Rankin Scale score of 0–1: adjusted odds ratio, 1.1 [95% CI, 0.6–2.2]; P =0.71). END 7d occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9–10.1) versus 20.4 hours (interquartile range, 7.8–34.4), respectively, P Conclusions: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END—particularly END due to artery-to-artery embolism—occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population.

Published
2022
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20. Prediction of Early Neurological Deterioration in Individuals With Minor Stroke and Large Vessel Occlusion Intended for Intravenous Thrombolysis Alone

Author

Aïcha Lyoubi, Charles Arteaga, Caroline Arquizan, Philippe Niclot, Aude Triquenot, Charlotte Rosso, Laurent Suissa, Laurie Fraticelli, Frédéric Klapczynski, Marion Boulanger, Christine Pires, Patrik Michel, Didier Leys, Philippe Smadja, Mathilde Delpech, Stéphane Vannier, Yves Berthezène, Sébastien Richard, Sébastien Gazzola, Serge Timsit, Valérie Wolff, Jérémie Papassin, Laurent Spelle, Christian Denier, Yannick Béjot, Jean-Louis Mas, Anne-Evelyne Vallet, Catherine Oppenheim, Séverine Debiais, Serge Bracard, Olivier Detante, Andreea Aignatoaie, Frédéric Philippeau, François Lun, Denis Sablot, Emmanuel Touzé, Valer Grigoras, Sébastien Marcel, Hervé Brunel, Laura Mechtouff, Hubert Desal, Mirjam Rachel Heldner, Bertrand Lapergue, Vincent Costalat, Serkan Cakmak, Duc-Long Duong, Isabelle Serre, François Mounier-Vehier, Audrey Courselle-Arnoux, Sébastien Soize, Ludovic Lucas, Pierre Agius, Sonia Alamowitch, Isabelle Girard Buttaz, Michel Piotin, Pierre Garnier, Gauthier Duloquin, Davide Strambo, Nicolas Bricout, Omar Bennani, Emmanuel Carrera, Marion Yger, Hilde Hénon, Jean-Philippe Cottier, Nicolae Crainic, Michael Obadia, Cécile Preterre, Guillaume Turc, Steven Hajdu, Pierre Seners, Mathieu Zuber, Jean-Claude Baron, C. Lamy, Wagih Ben Hassen, Claire Perrin, Claire Boutet, Matthieu Krug, Clement Tracol, Amélie Tuffal, Norbert Nighoghossian, Arnaud Malbranque, Jan Gralla, Yves Samson, Benoit Guillon, Alexandre Obadia, Nadia Laksiri, Ruben Tamazyan, Mylène Masson, Frédéric Clarençon, Canan Ozsancak, Fernando Pico, Gioia Mione, Simon Jung, Mohamed Chbicheb, Igor Sibon, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Foch [Suresnes], Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bern University Hospital [Berne] (Inselspital), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Saint Jean de Perpignan, Centre hospitalier [Valenciennes, Nord], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier de Saint-Nazaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Lens, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Métropole Savoie [Chambéry], Centre Hospitalier Régional d'Orléans (CHRO), CHU Rouen, Normandie Université (NU), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier René Dubos [Pontoise], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Strasbourg, Centre Hospitalier Universitaire [Rennes], Centre Hospitalier Fleyriat [Bourg en Bresse], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), MINOR-STROKE Collaborators : Sonia Alamowitch, Charles Arteaga, Omar Bennani, Yves Berthezene, Marion Boulanger, Claire Boutet, Serge Bracard, Nicolas Bricout, Hervé Brunel, Serkan Cakmak, Mohamed Chbicheb, Frédéric Clarençon, Vincent Costalat, Audrey Courselle-Arnoux, Séverine Debiais, Mathilde Delpech, Christian Denier, Hubert Desal, Olivier Detante, Gauthier Duloquin, Laurie Fraticelli, Sébastien Gazzola, Jan Gralla, Valer Grigoras, Benoit Guillon, Matthieu Krug, Steven Hajdu, Simon Jung, Frédéric Klapczynski, Didier Leys, François Lun, Arnaud Malbranque, Sébastien Marcel, Patrik Michel, Jean-Louis Mas, Mylène Masson, Norbert Nighoghossian, Michael Obadia, Catherine Oppenheim, Canan Ozsancak, Fernando Pico, Michel Piotin, Christine Pires, Sébastien Richard, Yves Samson, Isabelle Serre, Igor Sibon, Philippe Smadja, Laurent Spelle, Laurent Suissa, Serge Timsit, Emmanuel Touzé, Amélie Tuffal, Anne-Evelyne Vallet, Marion Yger, Stéphane Vannier, Mathieu Zuber., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Martinez Rico, Clara

Subjects
medicine.medical_specialty, medicine.medical_treatment, Population, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine.artery, Occlusion, medicine, 030212 general & internal medicine, 10. No inequality, education, 610 Medicine & health, Stroke, Original Investigation, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Retrospective cohort study, Thrombolysis, medicine.disease, ddc:616.8, Cohort, Cardiology, Neurology (clinical), Internal carotid artery, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Importance The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy. Objective To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO. Design, Setting, and Participants This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019. Main Outcomes and Measures ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause. Results Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively. Conclusions and Relevance The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.

Published
2021
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21. White Matter Tract Disruptions Predict Less Affected Hand Impairment Following Stroke: A Longitudinal Diffusion MRI Study

Author

Alexandre Krainik, Bernadette Naegele, Firdaus Fabrice Hannanu, Olivier Detante, Marc Hommel, and Assia Jaillard

Subjects
White matter, Longitudinal diffusion, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Internal medicine, medicine, Cardiology, medicine.disease, business, Stroke
Abstract

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

Published
2021
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22. Ventilatory Phenotypes of Sleep Apnea Subtypes at a Chronic Delay Following a First Ischemic Stroke: A Cross-Sectional Analysis of a Prospective Clinical-Based Cohort Study

Author

Olivier Detante, Sarah Alexandre, Marie Destors, Sébastien Bailly, J.L. Pépin, Rita Guzun, D Majorie, Sébastien Baillieul, and Renaud Tamisier

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Cross-sectional study, business.industry, Polysomnography, medicine.disease, Sleep in non-human animals, nervous system diseases, respiratory tract diseases, Internal medicine, Cohort, Ischemic stroke, medicine, Cardiology, Arterial blood, business, Stroke, Cohort study
Abstract

Introduction: Up to 40% of patients present an apnoea-hypopnoea index (AHI)g20/h at a chronic delay post-stroke. The ventilatory phenotype of sleep apnoea (SA) after stroke is not yet precisely described. Aim and objectives: To determine the prevalence and ventilatory phenotypic traits of obstructive (OSA), central (CSA), and coexistent OSA/CSA sleep apnoea at a chronic delay following a first-ever ischemic stroke. Methods: Cross-sectional analysis of a prospective, monocentric cohort conducted in a university hospital. 380 consecutive unselected first-ever stroke or transient ischemic attack (TIA) patients were screened over a 3-year period. Full-night polysomnography (PSG), arterial blood gases (ABG), and hypercapnic ventilatory response (HCVR) using a rebreathing test method were performed at a median [Q1; Q3] delay of 134.5 [97; 227.3] days following stroke onset. Results: PSG, ABG, and HCVR were obtained in 112 patients with a first-ever ischemic stroke. Using an AHI cut-off of 15 events.hour-1 of sleep, 56 (50.0%) patients were classified as having moderate to severe SA. Among them, 31 (55.4%) and 25 (44.6%) presented OSA and Coexistent OSA/CSA or CSA respectively. CO2 chemosensitivity significantly differed according to the presence or the type of SA. Coexistent OSA/CSA and CSA patients exhibited higher CO2 chemosensitivity levels compared to No SA patients (p=0.043). No difference was observed regarding ABG parameters. Conclusions: A higher CO2 chemosensitivity in Coexistent OSA/CSA and CSA patients following stroke may dedicate these patients to specific care and ventilatory support.

Published
2021
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23. Patent foramen ovale closure in stroke patients with migraine in the CLOSE trial. The CLOSE-MIG study

Author

Yannick Béjot, Benoit Guillon, Emmanuel Teiger, Caroline Arquizan, Serge Timsit, Olivier Detante, Geneviève Derumeaux, Emmanuel Touzé, Close investigators, Fabrice Vuillier, Sonia Alamowitch, Céline Guidoux, Gilles Chatellier, Denis Sablot, Pierre Aubry, Laurent Derex, Jean-Louis Mas, Anaïs Charles-Nelson, Sandrine Canaple, Evelyne Massardier, Igor Sibon, V. Domigo, Nelly Dequatre-Ponchelle, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Rouen, Normandie Université (NU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Registre Dijonnais des Accidents Vasculaires Cérébraux (AVC) - Dijon Stroke Registry, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Saint Jean de Perpignan, Agence Régionale de Santé Occitanie (ARS Occitanie), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Saint-Antoine [AP-HP], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Saint-Antoine], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, medicine.medical_specialty, Stroke patient, Aura, Septal Occluder Device, [SDV]Life Sciences [q-bio], Migraine Disorders, Foramen Ovale, Patent, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ischaemic stroke, medicine, Humans, 030212 general & internal medicine, Closure (psychology), Foramen ovale (heart), business.industry, Middle Aged, medicine.disease, Clinical trial, Stroke, medicine.anatomical_structure, Treatment Outcome, Neurology, Migraine, Cardiology, Patent foramen ovale, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Platelet Aggregation Inhibitors
Abstract

International audience; Background and purpose The efficacy of patent foramen ovale (PFO) closure to reduce the frequency of migraine attacks remains controversial. Methods This was a planned sub-study in migraine patients enrolled in a randomized, clinical trial designed to assess the superiority of PFO closure plus antiplatelet therapy over antiplatelet therapy alone to prevent stroke recurrence in patients younger than 60 years with a PFO-associated cryptogenic ischaemic stroke. The main outcome was the mean annual number of migraine attacks in migraine patients with aura and in those without aura, as recorded at each follow-up visit by study neurologists. Results Of 473 patients randomized to PFO closure or antiplatelet therapy, 145 (mean age 41.9 years; women 58.6%) had migraine (75 with aura and 70 without aura). Sixty-seven patients were randomized to PFO closure and 78 to antiplatelet therapy. During a mean follow-up of about 5 years, there were no differences between antiplatelet-only and PFO closure groups in the mean annual number of migraine attacks, both in migraine patients with aura (9.2 [11.9] vs. 12.0 [19.1], p = 0.81) and in those without aura (12.1 [16.1] vs. 11.8 [18.4], p > 0.999). There were no differences between treatment groups regarding cessation of migraine attacks, migraine-related disability at 2 years and use of migraine-preventive drugs during follow-up. Conclusions In young and middle-aged adults with PFO-associated cryptogenic stroke and migraine, PFO closure plus antiplatelet therapy did not reduce the mean annual number of migraine attacks compared to antiplatelet therapy alone, in migraine patients both with and without aura.

Published
2021
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24. Sleep-disordered breathing and ventilatory chemosensitivity in first ischaemic stroke patients: a prospective cohort study

Author

Marie Destors, Jean-Louis Pépin, Sébastien Bailly, Marjorie Dole, Olivier Detante, Rita Clin, Sébastien Baillieul, Renaud Tamisier, Sarah Alexandre, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), [GIN] Grenoble Institut des Neurosciences (GIN), Pôle Thorax et Vaisseaux [CHU Grenoble], ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), SALAS, Danielle, and MIAI @ Grenoble Alpes - - MIAI2019 - ANR-19-P3IA-0003 - P3IA - VALID

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.diagnostic_test, business.industry, [SDV]Life Sciences [q-bio], Polysomnography, medicine.disease, University hospital, respiratory tract diseases, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Cohort, Ischaemic stroke, Sleep disordered breathing, medicine, Breathing, Cardiology, Prospective cohort study, business, Stroke, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract

RationaleSleep-disordered breathing (SDB) is highly prevalent after stroke. The clinical and ventilatory chemosensitivity characteristics of SDB, namely obstructive, central and coexisting obstructive and central sleep apnoea (coexisting sleep apnoea) following stroke are poorly described.ObjectiveTo determine the respective clinical and ventilatory chemosensitivity characteristics of SDB at least 3 months after a first ischaemic stroke.MethodsCross-sectional analysis of a prospective, monocentric cohort conducted in a university hospital. 380 consecutive stroke or transient ischaemic attack patients were screened between December 2016 and December 2019.Measurements and main resultsFull-night polysomnography, and hypercapnic ventilatory response were performed at a median (Q1; Q3) time from stroke onset of 134.5 (97.0; 227.3) days. 185 first-time stroke patients were included in the analysis. 94 (50.8%) patients presented no or mild SDB (Apnoea-Hypopnoea Index ConclusionSDB in first-time stroke patients differ in their presentation by their respective clinical traits and ventilatory chemosensitivity characteristics. The heightened hypercapnic ventilatory response in coexisting and central sleep apnoea stroke patients may orientate them to specific ventilatory support.

Published
2021

25. Functional connectivity within the network of verticality

Author

Marc Hommel, Cédric Pichat, Monica Baciu, Camille Lemaire, Shenhao Dai, Céline Piscicelli, Assia Jaillard, Dominic Pérennou, Olivier Detante, Irina Gornushkina, Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Autonomie, Gérontologie, E-santé, Imagerie & Société [Grenoble] (AGEIS), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Dept of NeuroRehabilitation, CHU Grenoble Alpes, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Cannard, Christine

Subjects
0303 health sciences, Brain Mapping, Functional connectivity, Rehabilitation, Brain, Spatial cognition, [SCCO] Cognitive science, medicine.disease, Magnetic Resonance Imaging, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Space Perception, medicine, Visual Perception, Humans, Orthopedics and Sports Medicine, Psychology, Neuroscience, Stroke, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2020

26. Recovery of balance and gait after stroke is deteriorated by confluent white matter hyperintensities: Cohort study

Author

Shenhao Dai, Olivier Detante, Marc Hommel, Alexandre Krainik, Adélie Christiaens, Céline Piscicelli, Dominic Pérennou, Michel Thiebaut de Schotten, and Camille Lemaire

Subjects
medicine.medical_specialty, Rehabilitation, business.industry, medicine.medical_treatment, Stroke Rehabilitation, medicine.disease, Gait, Magnetic Resonance Imaging, White Matter, Hyperintensity, Cohort Studies, Stroke, Physical medicine and rehabilitation, Gait analysis, Cohort, Medicine, Humans, Orthopedics and Sports Medicine, business, Stroke recovery, Postural Balance, Balance (ability)
Abstract

White matter hyperintensities (WMHs) are well known to affect post-stroke disability, mainly by cognitive impairment. Their impact on post-stroke balance and gait disorders is unclear.We aimed to test the hypothesis that WMHs would independently deteriorate post-stroke balance and gait recovery.This study was performed in 210 individuals of the cohort Determinants of Balance Recovery After Stroke (DOBRAS), consecutively enrolled after a first-ever hemisphere stroke. Clinical data were systematically collected on day 30±3 (D30) post-stroke and at discharge from the rehabilitation ward. WMHs were searched on MRI, graded with the Fazekas scale, and dichotomized as no/mild (absence/sparse) or moderate/severe (confluent). The primary endpoint was the recovery of the single limb stance, assessed with the Postural Assessment Scale for Stroke (PASS). The secondary endpoint was the recovery of independent gait, assessed with the modified Fugl-Meyer Gait Assessment (mFMA). The adjusted hazard ratios (aHRs) of achievements of these endpoints by level of WMHs were estimated by using Cox models, accounting for other relevant clinical and imaging factors.Individuals with moderate/severe WMHs (n=86, 41%) had greater balance and gait disorders and were more often fallers than others (n=124, 59%). Overall, they had worse and slower recovery of single limb stance and independent gait (P0.001). Moderate/severe WMHs was the most detrimental factor for recovery of balance (aHR 0.46, 95% confidence interval [CI] 0.32-0.68, P0.001) and gait (0.51, 0.35-0.74, P0.001), along with age, stroke severity, lesion volume and disrupted corticospinal tract. With cerebral infarct, endovascular treatments had an independent positive effect, both on the recovery of balance (aHR 1.65, 95% CI 1.13-2.4, P=0.009) and gait (1.78, 1.24-2.55, P=0.002).WMHs magnify balance and gait disorders after stroke and worsen their recovery. They should be better accounted for in post-stroke rehabilitation, especially to help establish a prognosis of mobility. CLINICALTRIALS.NCT03203109.

Published
2020

27. Impaired cerebrovascular reactivity is associated with recurrent stroke in patients with severe intracranial arterial stenosis: A C02 BOLD fMRI study

Author

Johan Pietras, Eric Condamine, Olivier Detante, Jérémie Papassin, Olivier Heck, and Alexandre Krainik

Subjects
medicine.medical_specialty, Middle Cerebral Artery, Constriction, Pathologic, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, Internal medicine, medicine.artery, medicine, Humans, Radiology, Nuclear Medicine and imaging, Stroke, Survival analysis, Radiological and Ultrasound Technology, business.industry, Arterial stenosis, Cerebral Infarction, medicine.disease, Magnetic Resonance Imaging, Cerebral blood flow, Cerebrovascular Circulation, Middle cerebral artery, Cardiology, Neurology (clinical), Internal carotid artery, business, Perfusion, 030217 neurology & neurosurgery
Abstract

Background and Purpose Severe intracranial atherosclerotic stenosis (SIAS) remains at risk of recurrent ischemic events despite intensive medical management. Exhausted cerebrovascular reserve seems to be associated with higher risk of recurrent stroke. Materials and Methods We used whole brain MRI to estimate basal perfusion using dynamic susceptibility contrast and cerebrovascular reactivity (CVR) to hypercapnic challenge (CO2 inhalation) using BOLD contrast, in 20 patients with symptomatic SIAS (> 70%) of the middle cerebral artery (MCA) or the distal internal carotid artery. We studied relationships between individual clinical, biological, radiological baseline characteristics, recurrent ischemic events, basal perfusion parameters (mean transit time, delay, time to peak, cerebral blood flow and volume), and CVR measured in MCA territories (CVRMCA), and reported using laterality indices (LI). Results Ten patients had an impaired CVR with (|LI| CVRMCA ≥ 0.08). During a mean follow-up of 3.3 years, all recurrent ipsilateral ischemic events occurred within the first year. They were more frequent in impaired CVRMCA group (n = 7/10 patients) than in normal CVRMCA group (n = 1/10), with different survival curves (log rank, P = 0.007). Conclusion Impaired CVR is associated with an increased rate of recurrent stroke in patients with symptomatic SIAS. CVR mapping should be used as a well tolerated method to select higher-risk patients in further therapeutic trials such as endovascular procedures.

Published
2020

28. How to use stem cells for repair in stroke patients

Author

Claire Rome, Olivier Detante, and Jérémie Papassin

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Cell- and Tissue-Based Therapy, Regenerative Medicine, Bioinformatics, Regenerative medicine, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, medicine, Animals, Humans, Stroke, business.industry, Mesenchymal stem cell, Recovery of Function, medicine.disease, Neural stem cell, 3. Good health, Surgery, Transplantation, 030104 developmental biology, Neurology, Neurology (clinical), Stem cell, business, Stroke recovery, 030217 neurology & neurosurgery, Stem Cell Transplantation
Abstract

Regenerative cell therapy is a promising therapeutic strategy in neurology, most notably to improve stroke recovery. Although tolerability and feasibility have apparently been validated, many questions remain as to what is the best type of cells to use, the best route and the post-stroke delay for administration. Two main strategies have currently emerged: intravenous injection of mesenchymal stem cells with systemic trophic support; and intracerebral grafting of neural stem cells with brain repair effects at the lesion site. Multicenter clinical trials have just begun and are starting to assess the efficacy of these treatments on functional recovery. However, experimental studies also need to be conducted in parallel to precisely identify the mechanisms of action regarding the pathophysiology of brain plasticity , notably when stroke occurs with comorbidities. Such studies should also evaluate the potential of cell grafting combined with injectable biomaterials.

Published
2017
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29. Cortical lateralization and cardiac autonomic control. Insights from insular stroke and epilepsy

Author

Pascal Defaye, Olivier Detante, Victor Constantinescu, Cristian Dinu Popescu, Irina Constantinescu, Cătălina Arsenescu-Georgescu, Daniela Matei, and Dan Iulian Cuciureanu

Subjects
business.industry, Materials Science (miscellaneous), Dysautonomia, medicine.disease, Insular cortex, General Business, Management and Accounting, Sudden death, Industrial and Manufacturing Engineering, Lateralization of brain function, 03 medical and health sciences, Autonomic nervous system, Epilepsy, 0302 clinical medicine, nervous system, 030202 anesthesiology, medicine, Business and International Management, medicine.symptom, General Agricultural and Biological Sciences, business, Insula, Stroke, Neuroscience, 030217 neurology & neurosurgery
Abstract

Autonomic nervous system dysfunction is a common complication of stroke. Human studies and experimental data showed a hemispheric lateralization of autonomic activity concerning the forebrain and particularly the insular cortex. Insular cortex involvement is associated with more pronounced autonomic imbalance leading to life threatening arrhythmias and sudden death. We present two case reports of insular infarction in young patients without any cardiac comorbidity, illustrating a specific lateralized function of insula and its influence on the sympatho-vagal balance that implied differentiated therapeutic management after stroke. The right insular stroke was associated to sympathetic activation and left insular stroke was associated to parasympathetic predominance. The same lateralization of autonomic function with opposite effects on sympatho-vagal balance was also reported in two insular epilepsy cases, illustrating the fact that, beyond the controlling network, the cortical modulation of the autonomic nervous system is asymmetric. Identifying high risk patients prone to develop neurogenic cardiac complications, by better understanding of dysautonomia pathophysiology and consequent implementation of prophylactic and therapeutic interventions may significantly reduce mortality rate in stroke and epilepsy.

Published
2017
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30. Concordance of Time-of-Flight MRA and Digital Subtraction Angiography in Adult Primary Central Nervous System Vasculitis

Author

H. de Boysson, Christian Pagnoux, Emmanuel Touzé, M. Zuber, Caroline Arquizan, Gregoire Boulouis, Olivier Naggara, Loïc Guillevin, Boris Bienvenu, N. Dequatre, Achille Aouba, Olivier Detante, and Jean-Jacques Parienti

Subjects
Adult, Male, medicine.medical_specialty, Concordance, Magnetic resonance angiography, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Vasculitis, Central Nervous System, Aged, Retrospective Studies, medicine.diagnostic_test, Arterial stenosis, business.industry, Adult Brain, Angiography, Digital Subtraction, Retrospective cohort study, Digital subtraction angiography, Middle Aged, Neurovascular bundle, medicine.disease, eye diseases, body regions, cardiovascular system, Female, Neurology (clinical), Radiology, business, Vasculitis, Magnetic Resonance Angiography, 030217 neurology & neurosurgery, circulatory and respiratory physiology, Cohort study
Abstract

BACKGROUND AND PURPOSE: 3D-TOF-MRA and DSA are 2 available tools to demonstrate neurovascular involvement in primary central nervous system vasculitis. We aimed to compare the diagnostic concordance of vessel imaging using 3D-TOF-MRA and DSA in patients with primary central nervous system vasculitis. MATERIALS AND METHODS: We retrospectively identified all patients included in the French primary central nervous system vasculitis cohort of 85 patients who underwent, at baseline, both intracranial 3D-TOF-MRA and DSA in an interval of no more than 2 weeks and before treatment initiation. Two neuroradiologists independently reviewed all 3D-TOF-MRA and DSA imaging. Brain vasculature was divided into 25 arterial segments. Concordance between 3D-TOF-MRA and DSA for the identification of arterial stenosis was assessed by the Cohen κ Index. RESULTS: Thirty-one patients met the inclusion criteria, including 20 imaged with a 1.5T MR unit and 11 with a 3T MR unit. Among the 25 patients (81%) with abnormal DSA findings, 24 demonstrated abnormal 3D-TOF-MRA findings, whereas all 6 remaining patients with normal DSA findings had normal 3D-TOF-MRA findings. In the per-segment analysis, concordance between 1.5T 3D-TOF-MRA and DSA was 0.82 (95% CI, 0.75–0.93), and between 3T 3D-TOF-MRA and DSA, it was 0.87 (95% CI, 0.78–0.91). CONCLUSIONS: 3D-TOF-MRA shows a high concordance with DSA in diagnostic performance when analyzing brain vasculature in patients with primary central nervous system vasculitis. In patients with negative 3T 3D-TOF-MRA findings, the added diagnostic value of DSA is limited.

Published
2017
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31. Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?

Author

Jean-Louis Pépin, Sébastien Baillieul, Olivier Detante, Samarmar Chacaroun, Samuel Verges, and Stéphane Doutreleau

Subjects
0301 basic medicine, medicine.medical_specialty, Neurology, Physiology, Central nervous system, Stimulus (physiology), Neuroprotection, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Neuroplasticity, medicine, Animals, Humans, Hypoxia, Ischemic Preconditioning, Spinal Cord Injuries, Neurorehabilitation, business.industry, Hypoxia (medical), 030104 developmental biology, medicine.anatomical_structure, Brain Injuries, Anesthesia, Animal studies, medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

Central nervous system diseases are among the most disabling in the world. Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation as pharmacology treatments are often insufficiently effective. Conditioning the central nervous system has been proposed as a potential non-pharmacological neuro-therapeutic. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic conditioning has been investigated in several cellular and preclinical models and is now recognized as inducing endogenous mechanisms of neuroprotection. Ischemic, traumatic, or chronic neurodegenerative diseases can benefit from hypoxic conditioning strategies aiming at preventing the deleterious consequences or reducing the severity of the pathological condition (preconditioning) or aiming at inducing neuroplasticity and recovery (postconditioning) following central nervous system injury. Hypoxic conditioning can consist in single (sustained) or cyclical (intermittent, interspersed by short period of normoxia) hypoxia stimuli which duration range from few minutes to several hours and that can be repeated over several days or weeks. This mini-review addresses the existing evidence regarding the use of hypoxic conditioning as a potential innovating neuro-therapeutic modality to induce neuroprotection, neuroplasticity and brain recovery. This mini-review also emphasizes issues which remain to be clarified and future researches to be performed in the field. Impact statement Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation. Hypoxic conditioning may represent a harmless and efficient non-pharmacological new therapeutic modality in the field of neuroprotection and neuroplasticity, as supported by many preclinical data. Animal studies provide clear evidence for neuroprotection and neuroplasticity induced by hypoxic conditioning in several models of neurological disorders. These studies show improved functional outcomes when hypoxic conditioning is applied and provides important information to translate this intervention to clinical practice. Some studies in humans provide encouraging data regarding the tolerance and therapeutic effects of hypoxic conditioning strategies. The main issues to address in future research include the definition of the appropriate hypoxic dose and pattern of exposure, the determination of relevant physiological biomarkers to assess the effects of the treatment and the evaluation of combined strategies involving hypoxic conditioning and other pharmacological or non-pharmacological treatments.

Published
2017
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32. Patient eligibility for thrombectomy after acute stroke: Northern French Alps database analysis

Author

J. Papassin, Loic Belle, Olivier Detante, C. Vallot, F. Tahon, K. Boubagra, T. Atroun, G. Rodier, Fabrice Bing, Marc Hommel, S. Marcel, and I.M. Favre-Wiki

Subjects
Male, medicine.medical_specialty, Databases, Factual, medicine.medical_treatment, Database analysis, Eligibility Determination, Brain Ischemia, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Arterial occlusions, Epidemiology, Humans, Medicine, Thrombolytic Therapy, Registries, 030212 general & internal medicine, Symptom onset, Stroke, Aged, Retrospective Studies, Thrombectomy, Acute stroke, business.industry, Thrombolysis, Middle Aged, medicine.disease, Surgery, Mechanical thrombectomy, Treatment Outcome, Neurology, Cerebrovascular Circulation, Female, France, Neurology (clinical), business, Magnetic Resonance Angiography, 030217 neurology & neurosurgery
Abstract

Background Since 2015, the emergence of mechanical thrombectomy as standard care in acute stroke has involved organizational changes not only for stroke centers, but also for entire emergency regional networks. The aim of our study was to assess the proportion of ischemic stroke patients, admitted to stroke units in the Northern French Alps within the first 6 h of onset, eligible for thrombectomy. Methods This study retrospectively analyzed the clinical and radiological data of all acute stroke patients hospitalized at three stroke units of the Northern French Alps Emergency Network (RENAU) in 2014. Eligible patients had proximal arterial occlusions of the anterior and posterior cerebral circulation, as confirmed by brain imaging, which could be treated by thrombectomy within 6 h of symptom onset. Results Of the 435 cases of acute ischemic stroke, 152 patients were treated by intravenous thrombolysis (IV rtPA). Of these patients, 83 (55%) had intracranial occlusions and were eligible for combined thrombectomy. Of the 283 patients not treatable by IV rtPA, 32 patients (11%) were eligible for primary thrombectomy. Conclusion Thrombectomy could be performed in 26% of our acute ischemic stroke patients ( n = 115/435), and a large increase in endovascular procedures is expected over the next few years that will require close collaboration among all partners in the emergency networks. Using our RENAU stroke database, it will be possible to compare various factors contributing to effective activity.

Published
2017
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33. Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system

Author

Alexis Régent, Hubert de Boysson, Nicolas Gaillard, Christian Pagnoux, Mathieu Zuber, Loïc Guillevin, Caroline Arquizan, Olivier Naggara, Emanuel Touzé, Jean-Jacques Parienti, Achille Aouba, Antoine Néel, Gregoire Boulouis, Boris Bienvenu, and Olivier Detante

Subjects
030203 arthritis & rheumatology, medicine.medical_specialty, Multivariate analysis, medicine.diagnostic_test, business.industry, Odds ratio, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Maintenance therapy, Modified Rankin Scale, Internal medicine, Immunology, Cohort, Biopsy, medicine, Pharmacology (medical), Vasculitis, business, 030217 neurology & neurosurgery, Glucocorticoid, medicine.drug
Abstract

Objective We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS). Methods We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up. Results Ninety-seven patients [46 (47%) female, median age: 46 (18-78) years at diagnosis] were followed up for a median of 55 (5-198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3-18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P < 0.0001). Thirty-two (33%) patients experienced relapse [10 (22%) had received maintenance therapy while 22 (45%) had not, P = 0.01]; four subsequently died from relapse. In the multivariate analysis, maintenance therapy was the only independent predictor of good outcome [odds ratio (OR) = 7.8 (95% CI: 3.21, 20.36), P < 0.0001]. Conclusion The results of this long-term follow-up study suggest that maintenance therapy in adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings.

Published
2017
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34. Controlled clinical trials of cell therapy in stroke: Meta-analysis at six months after treatment

Author

Anaïck Moisan, Marc Hommel, Olivier Detante, and Assia Jaillard

Subjects
0301 basic medicine, medicine.medical_specialty, Funnel plot, Randomization, Cell- and Tissue-Based Therapy, Infarction, Cell therapy, 03 medical and health sciences, Route of administration, 0302 clinical medicine, Internal medicine, medicine, Humans, Stroke, business.industry, medicine.disease, Patient Outcome Assessment, Clinical trial, 030104 developmental biology, Neurology, Meta-analysis, Reperfusion, Controlled Clinical Trials as Topic, business, 030217 neurology & neurosurgery, Follow-Up Studies, Stem Cell Transplantation
Abstract

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.

Published
2017
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35. AMOBES (Active Mobility Very Early After Stroke)

Author

Alain P. Yelnik, Victorine Quintaine, Cedric Andriantsifanetra, Marie Wannepain, Peggy Reiner, Hélène Marnef, Mathilde Evrard, Elena Meseguer, Jean Pascal Devailly, Monica Lozano, Catherine Lamy, Florence Colle, Eric Vicaut, Cédric Andriantsifanétra, Margaux Barbi, Julien Brans, Hugues Chabriat, Jerome Mawet, Marie Wanepain, Pierre Amarenco, Agnes Dien, Balma Ortega, Sylvia Perez, Estelle Baudrat, Marine Blondel, Claire Kemlin, Anne Leger, Alexia Potet, Yves Samson, Raquel Acevedo, Bénédicte Broglin, Myriam Brulant, Cristina Lopez Lopez, Jean Louis Mas, Elena Melgosa, Cédric Monchaud, Julie Paquereau, David Aguilera, Claire Aymard, Simone Birnbaum, Bérangère Nguyen-Thuyet, Ruben Tamazyan, Mathieu Zuber, Christelle Hamon, Julien Le Tarnec, Béatrice Médée, Olivier Rémy-Néris, Serge Timsit, Jean Michel Graciès, Hassan Hosseini, Catherine Marie Loche, Emilie Rondeau, Sarah Troel, Marianne Barbieux, Olivier Detante, Katia Garambois, Adelaide Marquer, Grégoire Payen, Dominic Pérennou, Pascale Véjux, Antoine Thuriot, Xavier Ducrocq, Lionel Croci, Nathalie Khalil, Jean Paysant, Julie Bussone, Sara Mokadmi, Florence Reboullet, and Hélène Rousseau

Subjects
Male, 030506 rehabilitation, medicine.medical_specialty, Time Factors, medicine.medical_treatment, law.invention, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Randomized controlled trial, law, medicine, Humans, Prospective Studies, Active mobility, Mobility Limitation, Prospective cohort study, Stroke, Neurorehabilitation, Aged, Advanced and Specialized Nursing, Rehabilitation, business.industry, Stroke Rehabilitation, Recovery of Function, Middle Aged, medicine.disease, 3. Good health, Treatment Outcome, Quality of Life, Physical therapy, Female, Motor recovery, Neurology (clinical), 0305 other medical science, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Background and Purpose— Intensive physical therapy (PT) facilitates motor recovery when provided during a subacute stage after stroke. The efficiency of very early intensive PT has been less investigated. We aimed to investigate whether intensive PT conducted within the first 2 weeks could aid recovery of motor control. Methods— This multicentre randomized controlled trial compared soft PT (20-min/d apart from respiratory needs) and intensive PT (idem+45 minutes of intensive exercises/day) initiated within the first 72 hours after a first hemispheric stroke. The primary outcome was change in motor control between day (D) 90 and D0 assessed by the Fugl–Meyer score. Main secondary outcomes were number of days to walking 10 m unassisted, balance, autonomy, quality of life, and unexpected medical events. All analyses were by intent to treat. Results— We could analyze data for 103 of the 104 included patients (51 control and 52 experimental group; 64 males; median age overall 67 [interquartile range 59–77], 67 right hemispheric lesions, 80 ischemic lesions, National Institutes of Health Stroke Scale score ≥8 for 82%). Fugl–Meyer score increased over time ( P P =0.29) or interaction between treatment and time ( P =0.40). The median change in score between D90 and D0 was 27.5 (12–40) and 22.0 (12–56) for control and experimental groups ( P =0.69). Similar results were found for the secondary criteria. Conclusions— Very early after stroke, intensive exercises may not be efficient in improving motor control. This conclusion may apply to mainly severe stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01520636.

Published
2017
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36. Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke

Author

Marie-Jeanne Richard, Alexandre Krainik, F. Renard, I.M. Favre-Wiki, Anaïck Moisan, P. Antoine, Assia Jaillard, Patrice Davoine, Firdaus Fabrice Hannanu, Anne Chrispin, F. De Fraipont, G. Rodier, Sebastien Marcel, Marc Hommel, Antoine Thuriot, Laurent Lamalle, D. Perennou, Olivier Detante, Olivier Heck, K. Garambois, J.F. Le Bas, Félix Renard, Wilfried Vadot, Bernadette Naegele, Irène Troprès, J. Gere, M. Barbieux-Guillot, Thomas A. Zeffiro, and Sylvie Grand

Subjects
Adult, Male, medicine.medical_specialty, Brain activity and meditation, Cognitive Neuroscience, lcsh:Computer applications to medicine. Medical informatics, Brain mapping, lcsh:RC346-429, Functional Laterality, 050105 experimental psychology, 03 medical and health sciences, Superior temporal gyrus, 0302 clinical medicine, Physical medicine and rehabilitation, Parietal Lobe, Image Processing, Computer-Assisted, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Stroke, lcsh:Neurology. Diseases of the nervous system, Brain Mapping, Movement Disorders, Putamen, 05 social sciences, Motor Cortex, Regular Article, Recovery of Function, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Oxygen, medicine.anatomical_structure, Neurology, Cerebellar cortex, lcsh:R858-859.7, Regression Analysis, Female, Neurology (clinical), Psychology, Neuroscience, 030217 neurology & neurosurgery, Brodmann area, Motor cortex
Abstract

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

Published
2017
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37. Ischemic stroke location, sleep disordered breathing and sleep: Intermediate analysis of an observational prospective cohort

Author

Sébastien Bailly, J.-L. Pépin, Olivier Detante, Rita Guzun, M. Destors, Sarah Alexandre, Sébastien Baillieul, Renaud Tamisier, and F. Yonnet

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Epworth Sleepiness Scale, Apnea, Atrial fibrillation, Physical examination, Polysomnography, medicine.disease, nervous system diseases, respiratory tract diseases, Internal medicine, Intensive care, Cohort, medicine, Cardiology, cardiovascular diseases, medicine.symptom, Cardiology and Cardiovascular Medicine, Prospective cohort study, business
Abstract

Introduction Sleep disordered breathing (SDB) and ischemic stroke (IS) are intertwined pathologies. The topography of IS may interacts with SDB (vigilance, ventilatory and upper airway control). Objective To evaluate the association between stroke location and SDB after a first IS. Method Prospective monocentric cohort of patients aged 18–85 years, hospitalized in the Intensive Care Stroke Unit for a first IS, without any past neurovascular or sleep history. Stroke location was determined on the diagnostic brain imaging (magnetic resonance imaging or computerized tomography scan). At three months post-stroke (median delay [Q1;Q3] = 134 days [97;227]), patients underwent a clinical examination including validated sleep-related questionnaires and a full-night polysomnography (PSG), performed according to AASM recommendations. Results One hundred and forty-two patients were included. Patients were classified according to the absence or the presence of SDB [Apnea-Hypopnea Index (AHI) ≥ 15 events/hour of sleep]. Among them 53% had a SDB with a median AHI at 28/h [21; 43] (52% obstructive, 25% coexistent, 23% central). Post-IS patients were slightly symptomatic and did not differed (for SDB and non-SDB respectively, Epworth Sleepiness Scale 8 [4; 12] vs. 6 [4; 10] and Pichot Fatigue scale 8 [3; 18] vs. 11 [4; 20]). SDB patients were older (65 years old [55; 71] vs. 53 [48; 63]), and predominantly male (71%). Comorbidities were similar in both groups except for atrial fibrillation that was more frequent in the SDB group (14 (19%) vs 3 (5%), P = 0.01). The macrostructure of sleep was affected by SDB (in minute, light sleep = 16 [8; 31] vs 9.6 [5; 22] P = 0.01 and slow wave sleep = 4 [0; 9] vs 12 [5; 17] P Conclusion Those preliminary results suggest that cerebellar location might be associated with moderate to severe SDB. Moreover, post-stroke patients with IS were more prone to have atrial fibrillation.

Published
2020
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38. Topographie des infarctus cérébraux, syndrome d’apnées du sommeil et sommeil : résultats intermédiaires de cohorte observationnelle prospective

Author

Olivier Detante, M. Destors, Sarah Alexandre, Jean-Louis Pépin, Sébastien Baillieul, Renaud Tamisier, Rita Guzun, and Sébastien Bailly

Subjects
Behavioral Neuroscience, Neuropsychology and Physiological Psychology, Neurology, Cognitive Neuroscience, Neurology (clinical)
Abstract

Objectif Pathologies du sommeil et infarctus cerebral (IC) sont etroitement lies et possiblement la topographie de l’IC et la pathologie du sommeil interagissent (vigilance, commande ventilatoire et des voies aeriennes superieures). Objectif correlation entre topographie lesionnelle d’un premier IC et syndrome d’apnees du sommeil (SAS). Methodes Cohorte prospective monocentrique de patients âges de 18-85 ans, hospitalises en neuro-vasculaire pour un premier IC non hemorragique sans antecedent neurovasculaire ou sommeil. La topographie de l’IC etait definie sur l’imagerie au diagnostic (IRM ou TDM). A distance de l’IC, les patients realisaient un examen clinique, des auto-questionnaires et une polysomnographie (PSG) selon les recommandations de l’AASM (delai median de PSG [Q1 ;Q3] = 134 jours [97 ;227]). Resultats Sur 142 patients inclus, 53 % presentaient un SAS (IAH ≥ 15 evenements/heure de sommeil, IAH median a 28/h [21 ;43], 52 % obstructif, 25 % coexistant, 23 % central). Les patients post IC etaient peu symptomatiques et non differents (pour SAS et non SAS respectivement, Epworth a 8 [4 ;12] vs 6 [4 ;10] et Pichot 8 [3 ;18] vs 11 [4 ;20]). Les patients SAS etaient plus âges (65 ans [55 ;71] vs 53 [48 ;63]), et majoritairement masculins. Le SAS impactait la macrostructure du sommeil (en minute, Stade I = 16 [8 ;31] vs 9,6 [5 ;22] p = 0,01 et sommeil lent profond = 4 [0 ;9] vs 12 [5 ;17] p Conclusion Les resultats preliminaires semblent indiquer que la topographie de l’IC soit liee a la presence d’un SAS et possiblement sa typologie.

Published
2020
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39. Using tools effectively despite defective hand posture: A single-case study

Author

Assia Jaillard, Olivier Detante, François Osiurak, Mathieu Lesourd, and Bernadette Naegele

Subjects
Apraxias, Cognitive Neuroscience, Posture, Experimental and Cognitive Psychology, Single-subject design, Apraxia, 050105 experimental psychology, Lateralization of brain function, Functional Laterality, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 0501 psychology and cognitive sciences, Association (psychology), Transitive relation, Hand Strength, 05 social sciences, Motor control, Brain, medicine.disease, Hand, Neuropsychology and Physiological Psychology, Action (philosophy), Female, Psychology, Neurocognitive, 030217 neurology & neurosurgery, Psychomotor Performance, Cognitive psychology
Abstract

Apraxia, a cognitive disorder of motor control, can severely impair transitive actions (object-related) and may lead to action errors (e.g., rubbing a hammer on a nail instead of pounding it) and hand posture errors (e.g., grasping a tool in a wrong way). Here, we report a rare observation of a left-handed patient, left-lateralized for language, who developed a severe apraxia following a right brain lesion. Interestingly the patient showed a significant number of hand posture errors, while she perfectly demonstrated the actual use of tools. This case stressed the predictions made by the current theories of tool use. According to the manipulation-based approach, the hand posture errors should be associated with an impaired manipulation knowledge. According to the reasoning-based approach, the absence of action errors should be associated with spared mechanical knowledge. Moreover, to better understand the neurocognitive origins of the deficit observed in VF, we examined several potential brain lateralization of praxis functions. We initiated a systematic examination of VF's performance in several contexts of tool use allowing us to investigate which kinds of tool-use representations were potentially impaired in VF. Our investigation did not reveal any major deficit of manipulation knowledge. This can hardly account for the high frequency of hand posture errors, contrary to the predictions of the manipulation-based approach. In contrast, in line with the reasoning-based approach, mechanical knowledge was spared and can explain the absence of action errors. We also found that VF probably had a bilateral organization of praxis functions, but irrespective of the possible brain lateralization considered, none of which established a satisfactory association between manipulation knowledge and hand posture errors. Taken together, the manipulation-based approach fails to explain fully the deficit presented by this patient and should lead us to consider alternative explanations.

Published
2019

40. Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study

Author

O. Fain, Denis Sablot, C. Héroum, Thomas Ronzière, M. Gaudron, S. Di Legge, A. Lecluse, Olivier Detante, F. Dumont, S. Marcel, Sonia Alamowitch, D. Gobert, Isabelle Boccon-Gibod, Guillaume Marc, D. Smadja, Michael Obadia, D. Launay, S. Lefèvre, M. Sévin, Laurence Bouillet, Laurent Suissa, Stéphane Gayet, M. B. Vlaicu, Emilie Doche, Clara Vigneron, Nicolas Javaud, Igor Sibon, I. Ion, I. Arnaud, and P. Girard‐Madoux

Subjects
0301 basic medicine, Male, medicine.medical_specialty, medicine.medical_treatment, Bradykinin, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Brain Ischemia, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sex Factors, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, Thrombolytic Therapy, Angioedema, Aged, Mechanical ventilation, business.industry, Case-control study, Odds ratio, Thrombolysis, Stroke, 030104 developmental biology, chemistry, Case-Control Studies, Ischemic stroke, Cardiology, Female, France, medicine.symptom, business, Complication
Abstract

BACKGROUND Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P

Published
2019

41. Effect of perceptual-motor rehabilitation on speech recovery in two patients with chronic post-stroke aphasia

Author

Audrey Acher, Hélène Lœvenbruck, Diandra Fabre, Olivier Detante, Thomas Hueber, Emilie Cousin, Louise Kauffmann, Monica Baciu, Célise Haldin, Pascal Perrier, Dominic Pérennou, Assia Jaillard, Pierre Badin, Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Unité neurovasculaire, CHU Grenoble, GIPSA - Vision and Brain Signal Processing (GIPSA-VIBS), Département Images et Signal (GIPSA-DIS), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA - Cognitive Robotics, Interactive Systems, & Speech Processing (GIPSA-CRISSP), Département Parole et Cognition (GIPSA-DPC), IRMaGe (IRMaGe ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA - Perception, Contrôle, Multimodalité et Dynamiques de la parole (GIPSA-PCMD), Service de Médecine Physique et Réadaptation [CHU de Grenoble] (MPR), Centre Hospitalier Universitaire [Grenoble] (CHU), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was performed on the IRMaGe platform member of France Life Imaging network (grant ANR-11-INBS-0006), and HALDIN, Célise

Subjects
non-fluent, Cognitive Neuroscience, speech, 050105 experimental psychology, rehabilitation, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, 0501 psychology and cognitive sciences, langage, IRMf, AVC, Philosophy, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 05 social sciences, PMI, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, aphasie, [SCCO.LING]Cognitive science/Linguistics, aphasia, Neuropsychology and Physiological Psychology, rééducation, [SCCO.LING] Cognitive science/Linguistics, Humanities, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract

Recent studies on speech rehabilitation in aphasic patients show that a visual articulatory input can be useful for speech recovery, alongside the auditory input conventionally used. Moreover, the persistence of disorders, despite speech-therapy training generally undergone by these patients, emphasizes the need to develop new methods of speech rehabilitation. In this study, we evaluated a method of rehabilitation based on perceptual motor integration (PMI) – via the Ultraspeech player software – in two patients with chronic non-fluent aphasia after stroke. P1 showed a clinical picture of Broca’s aphasia, while P2 presented a global aphasia after stroke, which later transformed into a Broca’s aphasia. The Ultraspeech player software allows the visualization by the patient of reference tongue movements using ultrasound and video imaging for phonemes. The evaluation of the effect of this method was based on the comparison, before and after reeducation, of multimodal data allowing: a quantitative analysis of the acoustic parameters of the speech signal, a qualitative analysis of language performances and language scores, and a neurophysiological assessment of the anatomo-functional networks recruited in several language tasks. Our results show the efficiency of PMI in P1 but only a limited benefit in P2. In qualitative terms, naming, reading, word repetition, and rhyme detection improved in P1, while P2 declined in reading and rhyme detection. Quantitatively speaking, P1 improved in her production of vowels and consonants whereas P2 only partially improved in the quality of some consonants and vowels. In terms of cerebral correlates, in P1, we observed a modulation of the cerebral activity in language networks, in agreement with the behavioral improvement in speech and language, as well as efficient functional reorganization patterns. We discuss these results in the framework of theoretical models of speech motor control and we describe the conditions of PMI application in patients with non-fluent aphasia., Des études portant sur la rééducation de la parole chez des patients aphasiques montrent que l’ajout d’un support visuel, en complément du support auditif utilisé classiquement, peut être utile pour la récupération de la parole. Nous avons évalué une méthode de rééducation basée sur l’intégration perceptivo-motrice (IPM) via le logiciel Ultraspeech player, chez deux patientes présentant une aphasie non fluente chronique post-accident vasculaire cérébral (AVC). L’évaluation de l’effet de cette méthode s’est appuyée sur la comparaison, avant et après rééducation, de données multimodales permettant : une évaluation quantitative des paramètres acoustiques du signal de parole, une évaluation qualitative des performances langagières et scores de langage, et une évaluation neurophysiologique des réseaux recrutés dans des tâches langagières. Nos résultats montrent l’efficacité de l’IPM chez P1 mais un bénéfice limité chez P2. Qualitativement, la dénomination, la lecture, la répétition des mots et le jugement de rimes s’améliorent chez P1, tandis que P2 décline en lecture et jugement de rimes. Quantitativement, P1 améliore sa production de voyelles et consonnes alors que P2 s’améliore pour quelques consonnes et voyelles uniquement. En IRMf, nous observons, chez P1, une modulation de l’activité des réseaux langagiers, en accord avec l’amélioration comportementale du langage ainsi que des patrons de réorganisation fonctionnelle efficaces.

Published
2019
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42. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Author

Bruce C V Campbell, Charles B L M Majoie, Gregory W Albers, Bijoy K Menon, Nawaf Yassi, Gagan Sharma, Wim H van Zwam, Robert J van Oostenbrugge, Andrew M Demchuk, Francis Guillemin, Philip White, Antoni Dávalos, Aad van der Lugt, Kenneth S Butcher, Aboubaker Cherifi, Henk A Marquering, Geoffrey Cloud, Juan M Macho Fernández, Jeremy Madigan, Catherine Oppenheim, Geoffrey A Donnan, Yvo B W E M Roos, Jai Shankar, Hester Lingsma, Alain Bonafé, Hélène Raoult, María Hernández-Pérez, Aditya Bharatha, Reza Jahan, Olav Jansen, Sébastien Richard, Elad I Levy, Olvert A Berkhemer, Marc Soudant, Lucia Aja, Stephen M Davis, Timo Krings, Marie Tisserand, Luis San Román, Alejandro Tomasello, Debbie Beumer, Scott Brown, David S Liebeskind, Serge Bracard, Keith W Muir, Diederik W J Dippel, Mayank Goyal, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Lucie A van den Berg, Hester F Lingsma, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Vitor Mendes Pereira, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, Xavier Ducrocq, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Olivier Naggara, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Anand Dixit, Andrew Clifton, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, Clinical Neurophysiology, Weimar, Christian (Beitragende*r), Radiology and nuclear medicine, Rheumatology, ACS - Atherosclerosis & ischemic syndromes, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: MA AIOS Neurologie (9), The Royal Melbourne Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Stanford University, University of Calgary, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Universitat Autònoma de Barcelona (UAB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Alberta, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Monash University [Melbourne], St George’s University Hospitals, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dalhousie University [Halifax], Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], St. Michael's Hospital, University of California [Los Angeles] (UCLA), University of California, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Toronto Western Hospital, Hôpital Foch [Suresnes], Vall d'Hebron University Hospital [Barcelona], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Glasgow, Queen Elizabeth University Hospital (Glasgow), David Geffen School of Medicine [Los Angeles], University of California-University of California, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Radiology & Nuclear Medicine, Public Health, Neurology, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Pulmonary hypertension & thrombosis, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, Biomedical Engineering and Physics, APH - Personalized Medicine, APH - Quality of Care, and AMS - Restoration & Development

Subjects
SELECTION, COMPUTED TOMOGRAPHIC PERFUSION, Medizin, Perfusion scanning, 030204 cardiovascular system & hematology, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, REPERFUSION, Stroke, ComputingMilieux_MISCELLANEOUS, Thrombectomy, Aged, 80 and over, medicine.diagnostic_test, Penumbra, Endovascular Procedures, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Cerebral blood flow, Tissue Plasminogen Activator, INFARCT, Cardiology, Female, TRIAL, CT, medicine.medical_specialty, Perfusion Imaging, Neuroimaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Fibrinolytic Agents, ALTEPLASE, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Aged, business.industry, MECHANICAL THROMBECTOMY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Magnetic resonance imaging, Odds ratio, medicine.disease, Neurology (clinical), business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Fibrinolytic agent, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Published
2019
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43. Cell therapy in stroke—cautious steps towards a clinical treatment

Author

Olivier Detante, Keith W. Muir, and Jukka Jolkkonen

Subjects
0301 basic medicine, medicine.medical_specialty, Neurology, medicine.medical_treatment, Alternative medicine, Cell- and Tissue-Based Therapy, Translational Research, Biomedical, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Intensive care medicine, Psychiatry, Stroke, Clinical Trials as Topic, Rehabilitation, business.industry, General Neuroscience, Stem-cell therapy, Vascular surgery, medicine.disease, 3. Good health, Clinical trial, 030104 developmental biology, Neurology (clinical), Neurosurgery, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

In the future, stroke patients may receive stem cell therapy as this has the potential to restore lost functions. However, the development of clinically deliverable therapy has been slower and more challenging than expected. Despite recommendations by STAIR and STEPS consortiums, there remain flaws in experimental studies such as lack of animals with comorbidities, inconsistent approaches to experimental design, and concurrent rehabilitation that might lead to a bias towards positive results. Clinical studies have typically been small, lacking control groups as well as often without clear biological hypotheses to guide patient selection. Furthermore, they have used a wide range of cell types, doses, and delivery methods, and outcome measures. Although some ongoing and recent trial programs offer hints that these obstacles are now being tackled, the Horizon2020 funded RESSTORE trial will be given as an example of inconsistent regulatory requirements and challenges in harmonized cell production, logistic, and clinical criteria in an international multicenter study. The PISCES trials highlight the complex issues around intracerebral cell transplantation. Therefore, a better understanding of translational challenges is expected to pave the way to more successful help for stroke patients.

Published
2018

44. Sub-acute and Chronic Ischemic Stroke Lesion MRI Segmentation

Author

Olivier Detante, Senan Doyle, Olivier Heck, Assia Jaillard, Florence Forbes, and Michel Dojat

Subjects
medicine.diagnostic_test, Computer science, Atlas (topology), business.industry, 05 social sciences, Probabilistic logic, Pattern recognition, Magnetic resonance imaging, Sub acute, Fluid-attenuated inversion recovery, 050105 experimental psychology, Lesion, 03 medical and health sciences, 0302 clinical medicine, Ischemic stroke, medicine, 0501 psychology and cognitive sciences, Artificial intelligence, medicine.symptom, Hidden Markov random field, business, 030217 neurology & neurosurgery
Abstract

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.

Published
2018
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45. Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Author

Bruce C V Campbell, Wim H van Zwam, Mayank Goyal, Bijoy K Menon, Diederik W J Dippel, Andrew M Demchuk, Serge Bracard, Philip White, Antoni Dávalos, Charles B L M Majoie, Aad van der Lugt, Gary A Ford, Natalia Pérez de la Ossa, Michael Kelly, Romain Bourcier, Geoffrey A Donnan, Yvo B W E M Roos, Oh Young Bang, Raul G Nogueira, Thomas G Devlin, Lucie A van den Berg, Frédéric Clarençon, Paul Burns, Jeffrey Carpenter, Olvert A Berkhemer, Dileep R Yavagal, Vitor Mendes Pereira, Xavier Ducrocq, Anand Dixit, Helena Quesada, Jonathan Epstein, Stephen M Davis, Olav Jansen, Marta Rubiera, Xabier Urra, Emilien Micard, Hester F Lingsma, Olivier Naggara, Scott Brown, Francis Guillemin, Keith W Muir, Robert J van Oostenbrugge, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Debbie Beumer, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Nawaf Yassi, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Gagan Sharma, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Alain Bonafé, Reza Jahan, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G 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J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Gregory W Albers, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Sébastien Richard, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Hélène Raoult, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Martin M Brown, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Geoffrey Cloud, Andrew Clifton, Jeremy Madigan, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, University of Melbourne, University of Calgary, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Amsterdam [Amsterdam] (UvA), Universitat Autònoma de Barcelona (UAB), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, Neurology, Graduate School, Other Research, APH - Personalized Medicine, APH - Quality of Care, Biomedical Engineering and Physics, ARD - Amsterdam Reproduction and Development, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, Radiology & Nuclear Medicine, Public Health, Weimar, Christian (Beitragende*r), Molecular cell biology and Immunology, Pathology, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurovascular Disorders, Rheumatology, Beeldvorming, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: CARIM - R3.11 - Imaging, MUMC+: DA BV Medisch Specialisten Radiologie (9), Klinische Neurowetenschappen, and MUMC+: MA Neurologie (3)

Subjects
Male, medicine.medical_specialty, Sedation, Medizin, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Anesthesia, General, CONTROLLED-TRIAL, THERAPY, law.invention, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Randomized controlled trial, law, Modified Rankin Scale, Journal Article, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Humans, General anaesthesia, Stroke, Aged, Randomized Controlled Trials as Topic, Thrombectomy, Aged, 80 and over, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Odds ratio, MR, Middle Aged, Outcome and Process Assessment (Health Care), medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Surgery, Outcome and Process Assessment, Health Care, Meta-analysis, Observational study, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Meta-Analysis
Abstract

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.

Published
2018
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46. The future of stem cell therapy for stroke rehabilitation

Author

Olivier Detante, Cesar V. Borlongan, and Jukka Jolkkonen

Subjects
medicine.medical_specialty, Neurology, Rehabilitation, Combination therapy, business.industry, medicine.medical_treatment, Translational research, Stem-cell therapy, medicine.disease, University hospital, Article, medicine, Physical therapy, Neurology (clinical), Neurosurgery, business, Stroke
Abstract

Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612 USA University of Eastern Finland, Institute of Clinical Medicine – Neurology, Yliopistonranta 1 C, 70210 Kuopio, Finland University Hospital of Grenoble, Stroke Unit, Department of Neurology, CS 10217, 38043 Grenoble, France Inserm, U 836, BP 170, 38042 Grenoble, France University Grenoble Alpes, Grenoble Institute of Neurosciences, BP 170, 38042 Grenoble, France *Authors for correspondence: Tel: +1 813 974 3154; Fax: +1 813 974 3078; cborlong@health.usf.edu and, Tel: +358 40 355 2519; Fax: +358 17 163539; jukka.jolkkonen@uef.fi Currently what are the biggest challenges in the field of stem cell therapy for stroke rehabilitation? Borlongan: The biggest challenge is the coalescing cell therapy with rehabilitation therapy in an effort to realize improved outcomes in stroke patients. Indeed, in the recent Stem Cell Therapeutics as an Emerging Paradigm for Stroke or STEPS 3 meeting, a key theme that was advanced by the group is to examine stem cell therapy vis-a-vis with rehabilitation therapy to reveal not only stand-alone effects of each therapy [1,2], but to potentially assess the concept of combination therapy for stroke. Although stroke rehabilitation is well recognized in the clinic [3], most of the preclinical studies on stem cell therapy have not incorporated this rehabilitation effect in the experimental design. Accordingly, this lack of rehabilitation control arm in the laboratory represents as a major disconnect between the preclinical arena and the clinical setting, limiting the recognition of the potential benefits of stem cell therapy to stroke rehabilitation and vice versa. Notwithstanding, if we define rehabilitation as ‘exercise’, there are excellent studies in the laboratory that have assessed the beneficial role of exercise

Published
2015
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47. Fibromuscular dysplasia: what the radiologist should know: a pictorial review

Author

Olivier Detante, Adrian Kastler, Alexandre Krainik, F. Thony, L. Varennes, Florence Tahon, Emmanuel Touzé, Sylvie Grand, and J. P. Baguet

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Arterial dissection, business.industry, Pictorial Review, Interventional radiology, Fibromuscular dysplasia, Arteries, medicine.disease, Aneurysm, Familial hypertension, medicine.anatomical_structure, Ectasia, cardiovascular system, medicine, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Radiology, business, Artery, Rare disease, Neuroradiology
Abstract

Fibromuscular dysplasia (FMD) is an idiopathic, segmentary, non-inflammatory and non-atherosclerotic disease that can affect all layers of both small- and medium-calibre arteries. The prevalence of FMD is estimated between 4 and 6 % in the renal arteries and between 0.3 and 3 % in the cervico-encephalic arteries. FMD most frequently affects the renal, carotid and vertebral arteries, but it can theoretically affect any artery. Radiologists play an important role in the diagnosis of FMD, and good knowledge of FMD’s signs will certainly help reduce the delay between the first symptoms and diagnosis. The common string-of-beads aspect is well known, but less common presentations also have to be considered. These less common imaging findings include vascular loops, fusiform vascular ectasia, arterial dissection, aneurysm and subarachnoid haemorrhage. These radiologic presentations should be known by radiologists in order to diagnose possible FMD, particularly when present in young females or when associated with personal or familial hypertension, to reduce the delay between the onset of the first symptom and the final diagnosis. The patients have to be referred to specialised FMD centres for dedicated management. • Fibromuscular dysplasia is not a rare disease. • Radiologists should recognise less common presentations to orient specific management. • Vascular loops, fusiform vascular ectasia and a “string-of-beads” aspect are typical presentations. • Arterial dissection, aneurysm and subarachnoid haemorrhage are less typical radiologic presentations.

Published
2015
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48. Fisiopatologia dell’ischemia cerebrale

Author

M Barbieux, Emmanuel L. Barbier, Isabelle Favre, Assia Jaillard, Marc Hommel, Olivier Detante, K. Garambois, and Anaïck Moisan

Subjects
Physics, Humanities
Abstract

L’ischemia cerebrale (IC) rappresenta l’80% degli accidenti vascolari cerebrali (AVC), seconda causa di mortalita nel mondo. Essa fa seguito all’interruzione del flusso ematico in un’arteria cerebrale. Si definisce come una riduzione della pressione di perfusione cerebrale sotto la soglia di autoregolazione fisiologica del flusso ematico cerebrale, che conduce a un insufficiente apporto in ossigeno e in energia. Si tratta di un fenomeno che evolve molto rapidamente nel tempo e nello spazio, andando dal «silenzio elettrofisiologico» di neuroni ancora vitali (penombra) alla necrosi irreversibile (infarto). La risonanza magnetica o la TC di perfusione permettono di visualizzare in urgenza queste zone di IC. I meccanismi che inducono la morte cellulare (omeostasi di Ca2+, Na+/Cl–, K+ ed eccitotossicita, depolarizzazione peri-infartuale, stress ossidativo, infiammazione, ecc.) non sono limitati ai neuroni. Essi coinvolgono l’insieme dell’unita neurovascolare, gli oligodendrociti e la microglia. Inoltre, l’immunodepressione sistemica causata dall’AVC e responsabile di infezioni che peggiorano la prognosi funzionale. E necessaria una migliore comprensione integrativa «al di la del neurone» di questi fenomeni per sviluppare dei trattamenti limitati, a tutt’oggi, alla gestione specializzata delle AVC, alla riperfusione per trombolisi e all’emicraniectomia decompressiva per gli infarti estesi. Parallelamente ai meccanismi deleteri, esistono una neuroprotezione endogena iniziale e, poi, un recupero che dura diversi mesi. Questo recupero, facilitato dalla rieducazione, e legato a un compenso dei deficit e alla plasticita cerebrale: riorganizzazione dei circuiti danneggiati e neurosinaptogenesi in relazione con la glia e i microvasi all’interno di «nicchie neuro-oligo-vascolari» perilesionali. L’ottimizzazione di questa plasticita multicellulare e, oggi, l’obiettivo di trattamenti promettenti di medicina rigenerativa basati sull’utilizzo di fattori di crescita e di cellule staminali o differenziate (terapia cellulare).

Published
2015
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49. Speech recovery and language plasticity can be facilitated by Sensori-Motor Fusion training in chronic non-fluent aphasia. A case report study

Author

Hélène Lœvenbruck, Diandra Fabre, Thomas Hueber, Assia Jaillard, Pierre Badin, Pascal Perrier, Dominic Pérennou, Olivier Detante, Louise Kauffmann, Monica Baciu, Célise Haldin, Audrey Acher, Emilie Cousin, Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Unité neurovasculaire, CHU Grenoble, Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft, GIPSA - Cognitive Robotics, Interactive Systems, & Speech Processing (GIPSA-CRISSP), Département Parole et Cognition (GIPSA-DPC), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IRMaGe (IRMaGe ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA - Perception, Contrôle, Multimodalité et Dynamiques de la parole (GIPSA-PCMD), Dept of NeuroRehabilitation, CHU Grenoble Alpes, Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Badin, Pierre

Subjects
Linguistics and Language, Speech production, medicine.medical_specialty, medicine.medical_treatment, media_common.quotation_subject, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Audiology, Pronunciation, Speech Therapy, 050105 experimental psychology, Language and Linguistics, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, 03 medical and health sciences, Speech and Hearing, 0302 clinical medicine, Tongue, Feedback, Sensory, Aphasia, medicine, Humans, Speech, 0501 psychology and cognitive sciences, Articulatory gestures, media_common, Language, Speech disorders, Aphasia, Broca, Rehabilitation, Neuronal Plasticity, Rhyme, 05 social sciences, Magnetic Resonance Imaging, Lip, non-fluent aphasia, fusion therapy, Speech disorder, Female, Syllable, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Cognitive psychology, Sensori-motor
Abstract

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.

Published
2017
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50. Evaluation of parametric response mapping to assess therapeutic response to human mesenchymal stem cells after experimental stroke

Author

Olivier Detante, Emmanuel L. Barbier, Benjamin Lemasson, Alexandre Krainik, Rui He, Anaïck Moisan, and Chantal Rémy

Subjects
Male, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Cell- and Tissue-Based Therapy, Biomedical Engineering, lcsh:Medicine, 030218 nuclear medicine & medical imaging, Cell therapy, diffusion MRI, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, medicine, ischemic stroke, Effective diffusion coefficient, Animals, Humans, Stroke, Saline, mesenchymal stem cell, 030304 developmental biology, 0303 health sciences, Transplantation, medicine.diagnostic_test, business.industry, lcsh:R, Magnetic resonance imaging, Mesenchymal Stem Cells, Thrombolysis, Original Articles, Cell Biology, medicine.disease, Magnetic Resonance Imaging, Rats, Disease Models, Animal, parametric response map, perfusion MRI, cell therapy, Nuclear medicine, business, Stroke recovery, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

Stroke is the leading cause of disability in adults. After the very narrow time frame during which treatment by thrombolysis and mechanical thrombectomy is possible, cell therapy has huge potential for enhancing stroke recovery. Accurate analysis of the response to new therapy using imaging biomarkers is needed to assess therapeutic efficacy. The aim of this study was to compare 2 analysis techniques: the parametric response map (PRM), a voxel-based technique, and the standard whole-lesion approach. These 2 analyses were performed on data collected at 4 time points in a transient middle cerebral artery occlusion (MCAo) model, which was treated with human mesenchymal stem cells (hMSCs). The apparent diffusion coefficient (ADC), cerebral blood volume (CBV), and vessel size index (VSI) were mapped using magnetic resonance imaging (MRI). Two groups of rats received an intravenous injection of either 1 mL phosphate-buffered saline (PBS)-glutamine (MCAo-PBS, n = 10) or 3 million hMSCs (MCAo-hMSC, n = 10). One sham group was given PBS-glutamine (sham, n = 12). Each MRI parameter was analyzed by both the PRM and the whole-lesion approach. At day 9, 1 d after grafting, PRM revealed that hMSCs had reduced the fraction of decreased ADC (PRMADC−: MCAo-PBS 6.7% ± 1.7% vs. MCAo-hMSC 3.3% ± 2.4%), abolished the fraction of increased CBV (PRMCBV+: MCAo-PBS 16.1% ± 3.7% vs. MCAo-hMSC 6.4% ± 2.6%), and delayed the fraction of increased VSI (PRMVSI+: MCAo-PBS 17.5% ± 6.3% vs. MCAo-hMSC 5.4% ± 2.6%). The whole-lesion approach was, however, insensitive to these early modifications. PRM thus appears to be a promising technique for the detection of early brain changes following treatments such as cell therapy.

Published
2017
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