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2. An exploratory intervention study suggests clinical benefits of training in chronic stroke to be paralleled by changes in brain activity using repeated fMRI

Author

Landsmann B, Pinter D, Pirker E, Pichler G, Schippinger W, Weiss EM, Mathie G, Gattringer T, Fazekas F, and Enzinger C

Subjects
mobility, cognition, lacunar stroke, training, rehabilitation, neuronal plasticity, Geriatrics, RC952-954.6
Abstract

Barbara Landsmann,1,2 Daniela Pinter,2 Eva Pirker,1,2 Gerald Pichler,3 Walter Schippinger,3 Elisabeth M Weiss,1 Gabriel Mathie,2 Thomas Gattringer,2 Franz Fazekas,2 Christian Enzinger2,4 1Institute of Psychology, University of Graz, Graz, Austria; 2Department of Neurology, Medical University of Graz, Graz, Austria; 3Albert Schweitzer Clinic Graz, Graz, Austria; 4Division of Neuroradiology, Department of Radiology, Medical University of Graz, Graz, Austria Purpose: Previous studies demonstrated changes in sensorimotor network activation over time after stroke that have been interpreted as partly compensatory. Locomotor and balance trainings may improve both mobility and cognition even in chronic stroke and thereby impact on cerebral activation patterns. We here aimed at testing these assumptions in an exploratory study to inform subsequent larger intervention studies. Patients and methods: Eight patients (73.3±4.4 years) with a chronic lacunar stroke (mean interval 3.7 years after the acute event with a range from 2 to 4 years) and residual leg paresis leading to gait disturbance received a guided 5-week training focusing on mobility, endurance, and coordination. Before and afterward, they underwent clinical, neuropsychological, and gait assessments and brain MRI at 3 T including a functional ankle movement paradigm. Sixteen healthy controls (HCs; 68.8±5.4 years) followed the same protocol without intervention. Results: After training, patients had improved in mobility, memory, and delayed recall of memory. While cerebral activations in HC remained completely unaltered, patients showed increased activations in the right precentral gyrus, the right and left superior frontal gyri, and the right frontal lobe, with bipedal ankle movements after training. Conclusion: In this exploratory study of chronic stroke, we found not only significant effects of physical training on mobility but also distinct aspects of cognition already with a small number of highly selected patients. These improvements were paralleled by alterations in cerebral activity possibly reflecting neuronal plasticity. Larger studies including randomization are needed. Keywords: mobility, cognition, lacunar stroke, training, rehabilitation, neuronal plasticity

Published
2016

4. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke

Author

Jaworek, T, Xu, H, Gaynor, BJ, Cole, JW, Rannikmae, K, Stanne, TM, Tomppo, L, Abedi, V, Amouyel, P, Armstrong, ND, Attia, J, Bell, S, Benavente, OR, Boncoraglio, GB, Butterworth, A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez, J, Chen, Z, Chong, M, Cruchaga, C, Cushman, M, Danesh, J, Debette, S, Duggan, DJ, Durda, JP, Engstrom, G, Enzinger, C, Faul, JD, Fecteau, NS, Fernandez-Cadenas, I, Gieger, C, Giese, A-K, Grewal, RP, Grittner, U, Havulinna, AS, Heitsch, L, Hochberg, MC, Holliday, E, Hu, J, Ilinca, A, INVENT Consortium, Irvin, MR, Jackson, RD, Jacob, MA, Janssen, RR, Jimenez-Conde, J, Johnson, JA, Kamatani, Y, Kardia, SL, Koido, M, Kubo, M, Lange, L, Lee, J-M, Lemmens, R, Levi, CR, Li, J, Li, L, Lin, K, Lopez, H, Luke, S, Maguire, J, McArdle, PF, McDonough, CW, Meschia, JF, Metso, T, Muller-Nurasyid, M, O'Connor, TD, O'Donnell, M, Peddareddygari, LR, Pera, J, Perry, JA, Peters, A, Putaala, J, Ray, D, Rexrode, K, Ribases, M, Rosand, J, Rothwell, PM, Rundek, T, Ryan, KA, Sacco, RL, Salomaa, V, Sanchez-Mora, C, Schmidt, R, Sharma, P, Slowik, A, Smith, JA, Smith, NL, Wassertheil-Smoller, S, Soederholm, M, Stine, OC, Strbian, D, Sudlow, CL, Tatlisumak, T, Terao, C, Thijs, V, Torres-Aguila, NP, Tregouet, D-A, Tuladhar, AM, Veldink, JH, Walters, RG, Weir, DR, Woo, D, Worrall, BB, Hong, CC, Ross, O, Zand, R, Leeuw, F-ED, Lindgren, AG, Pare, G, Anderson, CD, Markus, HS, Jern, C, Malik, R, Dichgans, M, Mitchell, BD, Kittner, SJ, and Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC)

Subjects
Neurology & Neurosurgery, 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences
Abstract

BACKGROUND AND OBJECTIVES: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. METHODS: We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. RESULTS: We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). DISCUSSION: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.

Published
2022

7. A multicentric investigation of the diagnostic accuracy of cortical lesions and central vein sign in multiple sclerosis

Author

Cagol, A., Cortese, R., Barakovic, M., Schaedelin, S., Ruberte, E., Absinta, M., Barkhof, F., Calabrese, M., Marco Castellaro, Ciccarelli, O., Cocozza, S., Stefano, N., Enzinger, C., Filippi, M., Jurynczyk, M., Maggi, P., Mahmoudi, N., Montalban, X., Palace, J., Pontillo, G., Rocca, M. A., Ropele, S., Rovira, A., Schoonheim, M. M., Sowa, P., Strijbis, E., Wattjes, M. P., Wuerfel, J., Kappos, L., and Granziera, C.

Published
2022

8. The longitudinal relationship between fatigue, depression, anxiety, disability, and adherence with cognitive status in patients with early multiple sclerosis treated with interferon beta-1a

Author

Ballegooijen, H. van, Hiele, K. van der, Enzinger, C., Voer, G. de, and Visser, L.H.

Subjects
Neurology
Abstract

Cognitive dysfunction is common in multiple sclerosis and may worsen with reduced treatment adherence. We examined longitudinal relationships between anxiety, depression, fatigue, disability and adherence with cognitive status in patients with relapsing-remitting multiple sclerosis (MS) treated with interferon beta-1a in four countries.The Confidence study is a prospective study in 165 people with MS with four visits (baseline/12/24/36 months). Physical and psychological symptoms were assessed using standardized questionnaires. Adherence was calculated as the number of injections divided by number of expected injections. Cognitive status was assessed by the Brief Repeatable Battery of Neuropsychological Tests and converted to a global Z-score.At baseline, mean age was 35.7 ± 11 years and 66% were female (Our findings provide evidence for a longitudinal association between depression and low cognitive status in patients treated with interferon beta-1a in routine medical practice.

Published
2021

9. P.048 International MAGNIMS-CMSC-NAIMS consensus recommendations on the use of standardized MRI in MS

Author

Traboulsee, A, primary, Wattjes, M, additional, Ciccarelli, O, additional, Reich, D, additional, Banwell, B, additional, de Stefano, N, additional, Enzinger, C, additional, Fazekas, F, additional, Filippi, M, additional, Frederiksen, J, additional, Gasperini, C, additional, Hacohen, Y, additional, Kappos, L, additional, Li, DK, additional, Mankad, K, additional, Montalban, X, additional, Newsome, S, additional, Oh, J, additional, Palace, J, additional, Rocca, M, additional, Sastre-Garriga, J, additional, Tintore, M, additional, Vrenken, H, additional, Yours, T, additional, Barkhof, F, additional, and Rovira, A, additional

Published
2021
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10. The role of pontine lesion location in differentiating multiple sclerosis from vascular risk factor-related small vessel disease

Author

Geraldes, R., Jurynczyk, M., dos Passos, G. R., Pichler, A., Chung, K., Hagens, M., Ruggieri, S., Auger, C., Sastre-Garriga, J., Enzinger, C., Chard, D., Barkhof, F., Gasperini, C., Rovira, A., DeLuca, G., Palace, J., MAGNIMS Study, Group, Filippi, M., Rocca, M. A., Institut Català de la Salut, [Geraldes R, Juryńczyk M, Rodrigues dos Passos G] Nuffield Department of Clinical Neurosciences, Oxford, UK. [Pichler A] Department of Neurology, Medical University of Graz, Graz, Austria/Division of Neuroradiology, Vascular & Interventional Radiology, Medical University of Graz, Graz, Austria. [Chung K] NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London Institute of Neurology, London, UK. [Hagens M] MS Center Amsterdam, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. [Auger C, Rovira A] Secció de Neuroradiologia, Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sastre-Garriga J] Servei de Neurologia/ Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Neuroscience - Brain Imaging, Radiology and nuclear medicine, Geraldes, R., Jurynczyk, M., dos Passos, G. R., Pichler, A., Chung, K., Hagens, M., Ruggieri, S., Auger, C., Sastre-Garriga, J., Enzinger, C., Chard, D., Barkhof, F., Gasperini, C., Rovira, A., Deluca, G., Palace, J., MAGNIMS Study, Group, Filippi, M., and Rocca, M. A.

Subjects
medicine.medical_specialty, cerebral small vessel disease, differential diagnosis, imaging, Multiple sclerosis, Esclerosi múltiple, Disease, Vascular risk, Cervell - Vasos sanguinis - Malalties, Lesion, 03 medical and health sciences, 0302 clinical medicine, Short Reports, Risk Factors, Internal medicine, Pons, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::enfermedades de los pequeños vasos cerebrales [ENFERMEDADES], Medicine, Humans, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], 030304 developmental biology, 0303 health sciences, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Cerebral Small Vessel Diseases [DISEASES], business.industry, Brain, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], medicine.disease, Magnetic Resonance Imaging, Neurology, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Cardiology, Imatgeria per ressonància magnètica, Neurology (clinical), Small vessel, Differential diagnosis, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Esclerosi múltiple; Diagnòstic diferencial; Imatges Esclerosis múltiple; Diagnóstico diferencial; Imagen Multiple sclerosis; Differential diagnosis; Imaging Background: Differentiating multiple sclerosis (MS) from vascular risk factor (VRF)-small vessel disease (SVD) can be challenging. Objective and Methods: In order to determine whether or not pontine lesion location is a useful discriminator of MS and VRF-SVD, we classified pontine lesions on brain magnetic resonance imaging (MRI) as central or peripheral in 93 MS cases without VRF, 108 MS patients with VRF and 43 non-MS cases with VRF. Results: MS without VRF were more likely to have peripheral pons lesions (31.2%, 29/93) than non-MS with VRF (0%, 0/43) (Exp(B) = 29.8; 95% confidence interval (CI) = (1.98, 448.3); p = 0.014) but there were no significant differences regarding central pons lesions between MS without VRF (5.4%, 5/93) and non-MS with VRF patients (16.3%, 7/43) (Exp(B) = 0.89; 95% CI = (0.2, 3.94); p = 0.87). The presence of peripheral pons lesions discriminated between MS and VRF-SVD with 100% (95% CI = (91.8, 100)) specificity. The proportion of peripheral pons lesions in MS with VRF (30.5%, 33/108) was similar to that seen in MS without VRF (31.2%, 29/93, p = 0.99). Central lesions occurred in similar frequency in MS with VRF (8.3%, 9/108) and non-MS with VRF (16.3%, 7/43, p = 0.15). Conclusion: Peripheral pons lesion location is a good discriminator of MS from vascular lesions. The author(s) received no financial support for the research, authorship and/or publication of this article.

Published
2020

11. Evaluation of the Central Vein Sign as a Diagnostic Imaging Biomarker in Multiple Sclerosis

Author

Sinnecker T., Clarke M. A., Meier D., Enzinger C., Calabrese M., De Stefano N., Pitiot A., Giorgio A., Schoonheim M. M., Paul F., Pawlak M. A., Schmidt R., Kappos L., Montalban X., Rovira A., Evangelou N., Wuerfel J., MAGNIMS Study Group, Filippi M, Rocca M. A., Anatomy and neurosciences, Amsterdam Neuroscience - Neuroinfection & -inflammation, Sinnecker, T., Clarke, M. A., Meier, D., Enzinger, C., Calabrese, M., De Stefano, N., Pitiot, A., Giorgio, A., Schoonheim, M. M., Paul, F., Pawlak, M. A., Schmidt, R., Kappos, L., Montalban, X., Rovira, A., Evangelou, N., Wuerfel, J., MAGNIMS Study, Group, Filippi, M, and Rocca, M. A.

Subjects
Central Nervous System, Male, Imaging biomarker, diagnosis, Cluster Headache, Relapsing-Remitting, multiple sclerosis, 0302 clinical medicine, 80 and over, 030212 general & internal medicine, Aged, 80 and over, Clinically isolated syndrome, medicine.diagnostic_test, Lupus Vasculitis, Central Nervous System, Neuromyelitis Optica, Brain, Middle Aged, Magnetic Resonance Imaging, medicine.anatomical_structure, Biomarker (medicine), biomarker, Female, Radiology, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, Migraine Disorders, Lupus Vasculitis, Sensitivity and Specificity, Lesion, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, central vein sign, clinical 3T magnetic resonance imaging, medicine, Humans, Vein, Aged, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Correction, Magnetic resonance imaging, Case-Control Studies, Cerebral Veins, Cross-Sectional Studies, Demyelinating Diseases, Multiple Sclerosis, medicine.disease, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Importance: The central vein sign has been proposed as a specific imaging biomarker for distinguishing between multiple sclerosis (MS) and not MS, mainly based on findings from ultrahigh-field magnetic resonance imaging (MRI) studies. The diagnostic value of the central vein sign in a multicenter setting with a variety of clinical 3 tesla (T) MRI protocols, however, remains unknown.Objective: To evaluate the sensitivity and specificity of various central vein sign lesion criteria for differentiating MS from non-MS conditions using 3T brain MRI with various commonly used pulse sequences.Design, Setting, and Participants: This large multicenter, cross-sectional study enrolled participants (n = 648) of ongoing observational studies and patients included in neuroimaging research databases of 8 neuroimaging centers in Europe. Patient enrollment and MRI data collection were performed between January 1, 2010, and November 30, 2016. Data analysis was conducted between January 1, 2016, and April 30, 2018. Investigators were blinded to participant diagnosis by a novel blinding procedure.Main Outcomes and Measures: Occurrence of central vein sign was detected on 3T T2*-weighted or susceptibility-weighted imaging. Sensitivity and specificity were assessed for these MRI sequences and for different central vein sign lesion criteria, which were defined by the proportion of lesions with central vein sign or by absolute numbers of lesions with central vein sign.Results: A total of 606 participants were included in the study after exclusion of 42 participants. Among the 606 participants, 413 (68.2%) were women. Patients with clinically isolated syndrome and relapsing-remitting MS (RRMS) included 235 women (66.6%) and had a median (range) age of 37 (14.7-61.4) years, a median (range) disease duration of 2 (0-33) years, and a median (range) Expanded Disability Status Scale score of 1.5 (0-6.5). Patients without MS included 178 women (70.4%) and had a median (range) age of 54 (18-83) years. A total of 4447 lesions were analyzed in a total of 487 patients: 690 lesions in 98 participants with clinically isolated syndrome, 2815 lesions in 225 participants with RRMS, 54 lesions in 13 participants with neuromyelitis optica spectrum disorder, 54 lesions in 14 participants with systemic lupus erythematosus, 121 lesions in 29 participants with migraine or cluster headache, 240 lesions in 20 participants with diabetes, and 473 lesions in 88 participants with other types of small-vessel disease. The sensitivity was 68.1% and specificity was 82.9% for distinguishing MS from not MS using a 35% central vein sign proportion threshold. The 3 central vein sign lesion criteria had a sensitivity of 61.9% and specificity of 89.0%. Sensitivity was higher when an optimized T2*-weighted sequence was used.Conclusions and Relevance: In this study, use of the central vein sign at 3T MRI yielded a high specificity and a moderate sensitivity in differentiating MS from not MS; international, multicenter studies may be needed to ascertain whether the central vein sign-based criteria can accurately detect MS.

Published
2019

13. Short-term adaptation to a simple motor task: A physiological process preserved in multiple sclerosis

Author

Mancini, L., Ciccarelli, O., Manfredonia, F., Thornton, J.S., Agosta, F., Barkhof, F., Beckmann, C., De Stefano, N., Enzinger, C., Fazekas, F., Filippi, M., Gass, A., Hirsch, J.G., Johansen-Berg, H., Kappos, L., Korteweg, T., Manson, S.C., Marino, S., Matthews, P.M., Montalban, X., Palace, J., Polman, C., Rocca, M., Ropele, S., Rovira, A., Wegner, C., Friston, K., Thompson, A., and Yousry, T.

Published
2009
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14. Mind the gap: from neurons to networks to outcomes in multiple sclerosis

Author

Chard, D. T., Alahmadi, A. A. S., Audoin, B., Charalambous, T., Enzinger, C., Hulst, H. E., Rocca, M. A., Rovira, A., Sastre-Garriga, J., Schoonheim, M. M., Tijms, B., Tur, C., Gandini Wheeler-Kingshott, C. A. M., Wink, A. M., Ciccarelli, O., Barkhof, F., De Stefano, N., Filippi, M., Frederiksen, J. L., Gasperini, C., Kappos, L., Palace, J., Yousry, T., Vrenken, H., University College of London [London] (UCL), Department of Diagnostic Radiology, Faculty of Applied Medical Science, King Abdulaziz University (KAU), Jeddah, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Department of Neurology, Research Unit for Neuronal Repair and Plasticity, Medical University of Graz, Graz, Department of Radiology, Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, Graz, Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Neuroimaging Research Unit and Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Universitat Autònoma de Barcelona (UAB), Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Department of Neurology, Luton and Dunstable University Hospital, Luton, Università degli Studi di Pavia = University of Pavia (UNIPV), Brain MRI 3T Research Center, IRCCS Mondino Foundation, Pavia, Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Section of Neuroradiology, Department of Radiology Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Institutes of Neurology and Healthcare Engineering, University College London, London, Chard, Declan T, Alahmadi, Adnan A S, Audoin, Bertrand, Charalambous, Thali, Enzinger, Christian, Hulst, Hanneke E, Rocca, Maria A, Rovira, Àlex, Sastre-Garriga, Jaume, Schoonheim, Menno M, Tijms, Betty, Tur, Carmen, Gandini Wheeler-Kingshott, Claudia A M, Wink, Alle Meije, Ciccarelli, Olga, Barkhof, Frederik, MAGNIMS Study, Group, and Filippi, Massimo

Subjects
Multiple Sclerosis, Grey matter, Network topology, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Default mode network, ComputingMilieux_MISCELLANEOUS, Inflammation, Neurons, Artificial neural network, business.industry, Multiple sclerosis, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, medicine.disease, medicine.anatomical_structure, Neurology (clinical), Disconnection, Alzheimer's disease, Nerve Net, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

MRI studies have provided valuable insights into the structure and function of neural networks, particularly in health and in classical neurodegenerative conditions such as Alzheimer disease. However, such work is also highly relevant in other diseases of the CNS, including multiple sclerosis (MS). In this Review, we consider the effects of MS pathology on brain networks, as assessed using MRI, and how these changes to brain networks translate into clinical impairments. We also discuss how this knowledge can inform the targeting of MS treatments and the potential future directions for research in this area. Studying MS is challenging as its pathology involves neurodegenerative and focal inflammatory elements, both of which could disrupt neural networks. The disruption of white matter tracts in MS is reflected in changes in network efficiency, an increasingly random grey matter network topology, relative cortical disconnection, and both increases and decreases in connectivity centred around hubs such as the thalamus and the default mode network. The results of initial longitudinal studies suggest that these changes evolve rather than simply increase over time and are linked with clinical features. Studies have also identified a potential role for treatments that functionally modify neural networks as opposed to altering their structure.

Published
2021

15. Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper)

Author

Wiendl, H., Gold, R., Berger, T., Derfuss, T., Linker, R., Mäurer, M., Aktas, O., Baum, K., Berghoff, M., Bittner, S., Chan, A., Czaplinski, A., Deisenhammer, F., Di Pauli, F., Du Pasquier, R., Enzinger, C., Fertl, E., Gass, A., Gehring, K., Gobbi, C., Goebels, N., Guger, M., Haghikia, A., Hartung, H.P., Heidenreich, F., Hoffmann, O., Kallmann, B., Kleinschnitz, C., Klotz, L., Leussink, V.I., Leutmezer, F., Limmroth, V., Lünemann, J.D., Lutterotti, A., Meuth, S.G., Meyding-Lamadé, U., Platten, M., Rieckmann, P., Schmidt, S., Tumani, H., Weber, F., Weber, M.S., Zettl, U.K., Ziemssen, T., Zipp, F., and ‘Multiple Sclerosis Therapy Consensus Group' (MSTCG)

Subjects
disease-modifying therapy, guideline, multiple sclerosis, treatment recommendation
Abstract

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

Published
2021

16. Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

Author

Nogueira, R.G. Qureshi, M.M. Abdalkader, M. Martins, S.O. Yamagami, H. Qiu, Z. Mansour, O.Y. Sathya, A. Czlonkowska, A. Tsivgoulis, G. Aguiar de Sousa, D. Demeestere, J. Mikulik, R. Vanacker, P. Siegler, J.E. Kõrv, J. Biller, J. Liang, C.W. Sangha, N.S. Zha, A.M. Czap, A.L. Holmstedt, C.A. Turan, T.N. Ntaios, G. Malhotra, K. Tayal, A. Loochtan, A. Ranta, A. Mistry, E.A. Alexandrov, A.W. Huang, D.Y. Yaghi, S. Raz, E. Sheth, S.A. Mohammaden, M.H. Frankel, M. Bila Lamou, E.G. Aref, H.M. Elbassiouny, A. Hassan, F. Menecie, T. Mustafa, W. Shokri, H.M. Roushdy, T. Sarfo, F.S. Alabi, T.O. Arabambi, B. Nwazor, E.O. Sunmonu, T.A. Wahab, K. Yaria, J. Mohammed, H.H. Adebayo, P.B. Riahi, A.D. Sassi, S.B. Gwaunza, L. Ngwende, G.W. Sahakyan, D. Rahman, A. Ai, Z. Bai, F. Duan, Z. Hao, Y. Huang, W. Li, G. Li, W. Liu, G. Luo, J. Shang, X. Sui, Y. Tian, L. Wen, H. Wu, B. Yan, Y. Yuan, Z. Zhang, H. Zhang, J. Zhao, W. Zi, W. Leung, T.W. Chugh, C. Huded, V. Menon, B. Pandian, J.D. Sylaja, P.N. Usman, F.S. Farhoudi, M. Hokmabadi, E.S. Horev, A. Reznik, A. Sivan Hoffmann, R. Ohara, N. Sakai, N. Watanabe, D. Yamamoto, R. Doijiri, R. Tokuda, N. Yamada, T. Terasaki, T. Yazawa, Y. Uwatoko, T. Dembo, T. Shimizu, H. Sugiura, Y. Miyashita, F. Fukuda, H. Miyake, K. Shimbo, J. Sugimura, Y. Yagita, Y. Takenobu, Y. Matsumaru, Y. Yamada, S. Kono, R. Kanamaru, T. Yamazaki, H. Sakaguchi, M. Todo, K. Yamamoto, N. Sonoda, K. Yoshida, T. Hashimoto, H. Nakahara, I. Kondybayeva, A. Faizullina, K. Kamenova, S. Zhanuzakov, M. Baek, J.-H. Hwang, Y. Lee, J.S. Lee, S.B. Moon, J. Park, H. Seo, J.H. Seo, K.-D. Sohn, S.I. Young, C.J. Ahdab, R. Wan Zaidi, W.A. Aziz, Z.A. Basri, H.B. Chung, L.W. Ibrahim, A.B. Ibrahim, K.A. Looi, I. Tan, W.Y. Yahya, N.W. Groppa, S. Leahu, P. Al Hashmi, A.M. Imam, Y.Z. Akhtar, N. Pineda-Franks, M.C. Co, C.O. Kandyba, D. Alhazzani, A. Al-Jehani, H. Tham, C.H. Mamauag, M.J. Venketasubramanian, N. Chen, C.-H. Tang, S.-C. Churojana, A. Akil, E. Aykaç, Ö. Ozdemir, A.O. Giray, S. Hussain, S.I. John, S. Le Vu, H. Tran, A.D. Nguyen, H.H. Nhu Pham, T. Nguyen, T.H. Nguyen, T.Q. Gattringer, T. Enzinger, C. Killer-Oberpfalzer, M. Bellante, F. De Blauwe, S. Vanhooren, G. De Raedt, S. Dusart, A. Lemmens, R. Ligot, N. Pierre Rutgers, M. Yperzeele, L. Alexiev, F. Sakelarova, T. Bedeković, M.R. Budincevic, H. Cindric, I. Hucika, Z. Ozretic, D. Saric, M.S. Pfeifer, F. Karpowic, I. Cernik, D. Sramek, M. Skoda, M. Hlavacova, H. Klecka, L. Koutny, M. Vaclavik, D. Skoda, O. Fiksa, J. Hanelova, K. Nevsimalova, M. Rezek, R. Prochazka, P. Krejstova, G. Neumann, J. Vachova, M. Brzezanski, H. Hlinovsky, D. Tenora, D. Jura, R. Jurák, L. Novak, J. Novak, A. Topinka, Z. Fibrich, P. Sobolova, H. Volny, O. Krarup Christensen, H. Drenck, N. Klingenberg Iversen, H. Simonsen, C.Z. Truelsen, T.C. Wienecke, T. Vibo, R. Gross-Paju, K. Toomsoo, T. Antsov, K. Caparros, F. Cordonnier, C. Dan, M. Faucheux, J.-M. Mechtouff, L. Eker, O. Lesaine, E. Ondze, B. Peres, R. Pico, F. Piotin, M. Pop, R. Rouanet, F. Gubeladze, T. Khinikadze, M. Lobjanidze, N. Tsiskaridze, A. Nagel, S. Ringleb, P.A. Rosenkranz, M. Schmidt, H. Sedghi, A. Siepmann, T. Szabo, K. Thomalla, G. Palaiodimou, L. Sagris, D. Kargiotis, O. Klivenyi, P. Szapary, L. Tarkanyi, G. Adami, A. Bandini, F. Calabresi, P. Frisullo, G. Renieri, L. Sangalli, D. Pirson, A. Uyttenboogaart, M. van den Wijngaard, I. Kristoffersen, E.S. Brola, W. Fudala, M. Horoch-Lyszczarek, E. Karlinski, M. Kazmierski, R. Kram, P. Rogoziewicz, M. Kaczorowski, R. Luchowski, P. Sienkiewicz-Jarosz, H. Sobolewski, P. Fryze, W. Wisniewska, A. Wiszniewska, M. Ferreira, P. Ferreira, P. Fonseca, L. Marto, J.P. Pinho E Melo, T. Nunes, A.P. Rodrigues, M. Tedim Cruz, V. Falup-Pecurariu, C. Krastev, G. Mako, M. de Leciñana, M.A. Arenillas, J.F. Ayo-Martin, O. Cruz Culebras, A. Tejedor, E.D. Montaner, J. Pérez-Sánchez, S. Tola Arribas, M.A. Rodriguez Vasquez, A. Mayza, M. Bernava, G. Brehm, A. Machi, P. Fischer, U. Gralla, J. Michel, P.L. Psychogios, M.-N. Strambo, D. Banerjee, S. Krishnan, K. Kwan, J. Butt, A. Catanese, L. Demchuk, A.M. Field, T. Haynes, J. Hill, M.D. Khosravani, H. Mackey, A. Pikula, A. Saposnik, G. Scott, C.A. Shoamanesh, A. Shuaib, A. Yip, S. Barboza, M.A. Barrientos, J.D. Portillo Rivera, L.I. Gongora-Rivera, F. Novarro-Escudero, N. Blanco, A. Abraham, M. Alsbrook, D. Altschul, D. Alvarado-Ortiz, A.J. Bach, I. Badruddin, A. Barazangi, N. Brereton, C. Castonguay, A. Chaturvedi, S. Chaudry, S.A. Choe, H. Choi, J.H. Dharmadhikari, S. Desai, K. Devlin, T.G. Doss, V.T. Edgell, R. Etherton, M. Farooqui, M. Frei, D. Gandhi, D. Grigoryan, M. Gupta, R. Hassan, A.E. Helenius, J. Kaliaev, A. Kaushal, R. Khandelwal, P. Khawaja, A.M. Khoury, N.N. Kim, B.S. Kleindorfer, D.O. Koyfman, F. Lee, V.H. Leung, L.Y. Linares, G. Linfante, I. Lutsep, H.L. Macdougall, L. Male, S. Malik, A.M. Masoud, H. McDermott, M. Mehta, B.P. Min, J. Mittal, M. Morris, J.G. Multani, S.S. Nahab, F. Nalleballe, K. Nguyen, C.B. Novakovic-White, R. Ortega-Gutierrez, S. Rahangdale, R.H. Ramakrishnan, P. Romero, J.R. Rost, N. Rothstein, A. Ruland, S. Shah, R. Sharma, M. Silver, B. Simmons, M. Singh, A. Starosciak, A.K. Strasser, S.L. Szeder, V. Teleb, M. Tsai, J.P. Voetsch, B. Balaguera, O. Pujol Lereis, V.A. Luraschi, A. Almeida, M.S. Cardoso, F.B. Conforto, A. De Deus Silva, L. Varrone Giacomini, L. Oliveira Lima, F. Longo, A.L. Magalhães, P.S.C. Martins, R.T. Mont'alverne, F. Mora Cuervo, D.L. Costa Rebello, L. Valler, L. Zetola, V.F. Lavados, P.M. Navia, V. Olavarría, V.V. Almeida Toro, J.M. Amaya, P.F.R. Bayona, H. Corredor, A. Rivera Ordonez, C.E. Mantilla Barbosa, D.K. Lara, O. Patiño, M.R. Diaz Escobar, L.F. Dejesus Melgarejo Fariña, D.E. Cardozo Villamayor, A. Zelaya Zarza, A.J. Barrientos Iman, D.M. Rodriguez Kadota, L. Campbell, B. Hankey, G.J. Hair, C. Kleinig, T. Ma, A. Tomazini Martins, R. Sahathevan, R. Thijs, V. Salazar, D. Yuan-Hao Wu, T. Haussen, D.C. Liebeskind, D. Yavagal, D.R. Jovin, T.G. Zaidat, O.O. Nguyen, T.N. SVIN COVID-19 Global Stroke Registry SVIN COVID-19 Global Stroke Registry

Abstract

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months. © 2021 American Academy of Neurology.

Published
2021

18. Reproducibility of fMRI in the clinical setting: Implications for trial designs

Author

Bosnell, R., Wegner, C., Kincses, Z.T., Korteweg, T., Agosta, F., Ciccarelli, O., De Stefano, N., Gass, A., Hirsch, J., Johansen-Berg, H., Kappos, L., Barkhof, F., Mancini, L., Manfredonia, F., Marino, S., Miller, D.H., Montalban, X., Palace, J., Rocca, M., Enzinger, C., Ropele, S., Rovira, A., Smith, S., Thompson, A., Thornton, J., Yousry, T., Whitcher, B., Filippi, M., and Matthews, P.M.

Published
2008
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37. Acute Cerebrovascular Disease in the Young: The Stroke in Young Fabry Patients Study

Author

Rolfs, Arndt, Fazekas, Franz, Grittner, Ulrike, Dichgans, Martin, Martus, Peter, Holzhausen, Martin, Böttcher, Tobias, Heuschmann, Peter U., Tatlisumak, Turgut, Tanislav, Christian, Jungehulsing, Gerhard J., Giese, Anne-Katrin, Putaala, Jukaa, Huber, Roman, Bodechtel, Ulf, Lichy, Christoph, Enzinger, Christian, Schmidt, Reinhold, Hennerici, Michael G., Kaps, Manfred, Kessler, Christof, Lackner, Karl, Paschke, Eduard, Meyer, Wolfgang, Mascher, Hermann, Riess, Olaf, Kolodny, Edwin, Norrving, Bo, Rolfs, A, Ginsberg, M, Hennerici, MG, Kessler, C, Kolodny, E, Martus, P, Norrving, B, Ringelstein, EB, Rothwell, PM, Venables, G, Bornstein, N, deDeyn, P, Dichgans, M, Fazekas, F, Markus, H, Rie, O, Biedermann, C, Böttcher, T, Brüderlein, K, Burmeister, J, Federow, I, König, F, Makowei, G, Niemann, D, Rolfs, A, Rösner, S, Zielke, S, Grittner, U, Martus, P, Holzhausen, M, Fazekas, F, Enzinger, C, Schmidt, R, Ropele, S, Windisch, M, Sterner, E, Bodamer, O, Fellgiebel, A, Hillen, U, Jonas, L, Kampmann, C, Kropp, P, Lackner, K, Laue, M, Mascher, H, Meyer, W, Paschke, E, Weidemann, F, Berrouschot, J, Stoll, A, Rokicha, A, Sternitzky, C, Thomä, M, DeDeyn, PP, Sheorajpanday, R, De Brabander, I, Yperzeele, L, Brouns, R, Oschmann, P, Pott, M, Schultes, K, Schultze, C, Hirsekorn, J, Jungehulsing, GJ, Villringer, A, Schmidt, W, Liman, T, Nowe, T, Ebinger, M, Wille, A, Loui, H, Objartel, A, übelacker, A, Mette, R, Jegzentis, K, Nabavi, DG, Crome, O, Bahr, D, Ebke, M, Platte, B, Kleinen, C, Mermolja Gunther, K, Heide, W, Pape, O, Hanssen, JR, Stangenberg, D, Klingelhofer, J, Schmidt, B, Schwarz, S, Schwarze, J, Frandlih, L, Iwanow, J, Steinbach, I, Krieger, D, Boysen, G, Leth Jeppesen, L, Petersen, A, Reichmann, H, Becker, U, Dzialkowski, I, Hentschel, H, Lautenschlager, C, Hanso, H, Gahn, G, Ziemssen, T, Fleischer, K, Sehr, B, McCabe, DJH, Tobin, O, Kinsella, J, Murphy, RP, Jander, S, Hartung, HP, Siebler, M, Bottcher, C, Kohne, A, Platzen, J, Brosig, TC, Rothhammer, V, Henseler, C, Neumann-Haefelin, T, Singer, OC, Ermis, U, dos Santos, IMRM, Schuhmann, C, van de Loo, S, Kaps, M, Allendorfer, J, Tanislav, C, Brandtner, M, Muir, K, Dani, K, MacDougall, N, Smith, W, Rowe, A, Welch, A, Fazekas, F, Schrotter, G, Krenn, U, Horner, S, Pendl, B, Pluta-Fuerst, A, Trummer, U, Kessler, C, Chatzopoulos, M, v Sarnowski, Bettina, Schminke, Ulf, Link, T, Khaw, A, Nieber, E, Zierz, S, Muller, T, Wegener, N, Wartenberg, K, Gaul, C, Richter, D, Rosenkranz, M, Krützelmann, AC, Hoppe, J, Choe, CU, Narr, S, Magnus, TU, Thomalla, G, Leypoldt, F, Otto, D, Lichy, C, Hacke, W, Barrows, RJ, Tatlisumak, T, Putaala, J, Curtze, S, Metso, M, Willeit, J, Furtner, M, Spiegel, M, Knoflach, MH, Prantl, B, Witte, OW, Brämer, D, Günther, A, Prell, T, Herzau, C, Aurich, K, Deuschl, G, Wodarg, F, Zimmermann, P, Eschenfelder, CC, Levsen, M, Weber, JR, Marecek, SM, Schneider, D, Michalski, D, Kloppig, W, Küppers-Tiedt, L, Schneider, M, Schulz, A, Matzen, P, Weise, C, Hobohm, C, Meier, H, Langos, R, Urban, D, Gerhardt, I, Thijs, V, Lemmens, R, Marcelis, E, Hulsbosch, C, Aichner, F, Haring, HP, Bach, E, Machado Candido, J, e Silva, AA, Lourenco, M, de Sousa, AIM, Derex, L, Cho, TH, Díez-Tejedor, E, Fuentes, B, Martínez-Sanchez, P, Pérez-Guevara, MI, Hamer, H, Metz, A, Hallenberger, K, Müller, P, Baron, P, Bersano, A, Gattinoni, M, Vella, N, Mallia, M, Jauss, M, Adam, L, Heidler, F, Gube, C, Kiszka, M, Dichgans, M, Karpinska, A, Mewald, Y, Straub, V, Dörr, A, Zollver, A, Ringelstein, EB, Schilling, M, Borchert, A, Preuth, N, Duning, T, Kuhlenbäumer, G, Schulte, D, Rothwell, PM, Marquardt, L, Schlachetzki, F, Boy, S, Mädl, J, Ertl, GM, Fehm, NPR, Stadler, C, Benecke, R, Dudesek, A, Kolbaske, S, Lardurner, G, Sulzer, C, Zerbs, A, Lilek, S, Walleczek, AM, Sinadinowska, D, Janelidze, M, Beridze, M, Lobjanidze, N, Dzagnidze, A, Melms, A, Horber, K, Fink, I, Liske, B, Ludolph, AC, Huber, R, Knauer, K, Hendrich, C, Raubold, S, Czlonkowska, A, Baranowska, A, Blazejewska-Hyzorek, B, Lang, W, Kristoferitsch, W, Ferrari, J, Ulrich, E, Flamm-Horak, A, Lischka-Lindner, A, Schreiber, W, Demarin, V, Tranjec, Z, Bosner-Puretic, M, Jurašić, MJ, Basic Kes, V, Budisic, M, and Kopacevic, L

Published
2013
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42. Monogenic cerebral small‐vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology

Author

Mancuso, M., primary, Arnold, M., additional, Bersano, A., additional, Burlina, A., additional, Chabriat, H., additional, Debette, S., additional, Enzinger, C., additional, Federico, A., additional, Filla, A., additional, Finsterer, J., additional, Hunt, D., additional, Lesnik Oberstein, S., additional, Tournier‐Lasserve, E., additional, and Markus, H. S., additional

Published
2020
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48. Relating functional changes during hand movement to clinical parameters in patients with multiple sclerosis in a multi-centre fMRI study

Author

Wegner, C., Filippi, M., Korteweg, T., Beckmann, C., Ciccarelli, O., De Stefano, N., Enzinger, C., Fazekas, F., Agosta, F., Gass, A., Hirsch, J., Johansen-Berg, H., Kappos, L., Barkhof, F., Polman, C., Mancini, L., Manfredonia, F., Marino, S., Miller, D. H., Montalban, X., Palace, J., Rocca, M., Ropele, S., Rovira, A., Smith, S., Thompson, A., Thornton, J., Yousry, T., and Matthews, P. M.

Published
2008

50. Creating accurate reference segmentations of deep GM structures in MS patients by fast semi-automated outlining

Author

Sitter, A., Bartel, F., Palotai, M., Burggraaff, J., Liu, Y., Simoes, J., Ruggieri, S., Schregel, K., Pinzon, A. Morales, Ropele, S., Rocca, M. A., Gasperini, C., Gallo, A., Schoonheimm, M., Amann, M., Yiannakas, M., Wattjes, M. P., Sastre-Garriga, J., Kappos, L., Massimo Filippi, Enzinger, C., Ciccarelli, O., Frederiksen, J., Barkhof, F., Guttmann, C. R. G., Munck, J. C., Vrenken, H., Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Neurology, Medical psychology, Other Research, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer biology and immunology, and Amsterdam Neuroscience - Neurovascular Disorders

Published
2018

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