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1. Optical coherence tomography reflects clinically relevant gray matter damage in patients with multiple sclerosis

Author

Cagol, A., Fuertes, N.C., Stoessel, M., Barakovic, M., Schaedelin, S., D'Souza, M., Würfel, J., Brandt, A.U., Kappos, L., Sprenger, T., Naegelin, Y., Kuhle, J., Granziera, C., and Papadopoulou, A.

Subjects
Function and Dysfunction of the Nervous System
Abstract

BACKGROUND: Retinal degeneration leading to optical coherence tomography (OCT) changes is frequent in patients with multiple sclerosis (PwMS). OBJECTIVE: To investigate associations among OCT changes, MRI measurements of global and regional brain volume loss, and physical and cognitive impairment in PwMS. METHODS: 95 PwMS and 52 healthy controls underwent OCT and MRI examinations. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness and ganglion cell/inner plexiform layer (GCIPL) volume were measured. In PwMS disability was quantified with the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). Associations between OCT, MRI, and clinical measures were investigated with multivariable regression models. RESULTS: In PwMS, pRNFL and GCIPL were associated with the volume of whole brain (p

Published
2023

2. Comparative effectiveness of autologous haematopoietic stem cell transplantation vs. fingolimod, ocrelizumab and natalizumab in relapsing-remitting MS

Author

Atkins, H., Burman, J., Massey, J., Sutton, I., Withers, B., Macdonell, R., Grigg, A., Torkildsen, O., Bo, L., Lehmann, A., Horakova, D., Havrdova, E., Krasulova, E., Trneny, M., Kozak, T., van der Walt, A., Butzkueven, H., McCombe, P., Van Wijmeersch, B., Buzzard, K., Skibina, O., Lechner-Scott, J., Willekens, B., Barnett, M., Cartechini, E., Ozakbas, S., Alroughani, R., Izquierdo, G., Boz, C., Kalincik, T., Sharman, S., Roos, I., Freedman, M., Eichau, S., Snowden, J., Sharrack, B., Turkoglu, R., Prevost, J., Slee, M., Soysal, A., Khoury, S., Lugaresi, A., Onofrj, M., Grammond, P., Duquette, P., Girard, M., Prat, A., Terzi, M., Patti, F., and Kuhle, J.

Published
2022

3. Emulating randomized clinical trials in relapsing-remitting multiple sclerosis with nonrandomized real-world evidence: an application using data from the MSBase registry

Author

Karabudak, R., Boz, C., Khoury, S., Girard, M., Turkoglu, R., Soysal, A., Alroughani, R., Terzi, M., Horakova, D., Havrdova, E., Ozakbas, S., Ponzano, M., Grammond, P., Yamout, B., Kalincik, T., Prat, A., Eichau, S., Izquierdo, G., Kuhle, J., Patti, F., Lechner-Schott, J., Sormani, M. P., Butzkueven, H., van der Walt, A., and Signori, A.

Published
2022

4. Early non-disabling relapses are associated with a higher risk of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Coles, A., Daruwalla, C., Shaygannejad, V., Ozakbas, S., Havrdova, E. K., Alroughani, R., Patti, F., Onofrj, M., Eichau, S., Girard, M., Grand'Maison, F., Yamout, B., Sajedi, S. A., Amato, M. P., Altintas, A., Skibina, O., Grammond, P., Butzkueven, H., Maimone, D., Lechner-Scott, J., Soysal, A., John, N., Gerlach, O., Iuliano, G., Foschi, M., Van Pesch, V., Cartechini, E., Kuhle, J., Sa, M. J., Kermode, A., Gouider, R., Hodgkinson, S., McCombe, P., Sanchez-Menoyo, J. L., Singhal, B., Blanco, Y., Hughes, S., McGuigan, C., Taylor, B., Habek, M., Al-Asmi, A., Mihaela, S., Castillo Trivino, T., Al-Harbi, T., Rojas, J. I., Gray, O., Khurana, D., Van Wijmeersch, B., Kalincik, T., and Brown, J. W. L.

Published
2022

5. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable

Author

Butler, E., Van Pesch, V., Shalaby, N., Kermode, A., Maimone, D., Blanco, Y., Altintas, A., Turkoglu, R., Butzkueven, H., Van der Walt, A., Skibina, O., Buzzard, K., Lechner-Scott, J., Grammond, P., Khoury, S. J., Yamout, B., Grand'Maison, F., Karabudak, R., Amato, M. P., Terzi, M., Duquette, P., Girard, M., Prat, A., Weinstock-Guttman, B., Lugaresi, A., Onofrj, M., Zakaria, M., Boz, C., Eichau, S., Izquierdo, G., Shaygannejad, V., Alroughani, R., Patti, F., Havrdova, E. K., Horakova, D., Ozakbas, S., Sanchez, M. Martinez, Malpas, C., Simpson-Yap, S., Roos, I., Sharmin, S., Sidhom, Y., Gouider, R., Gerlach, O., Soysal, A., Barnett, M., Kuhle, J., Hughes, S., Sa, M. Jose, and Kalincik, T.

Published
2022

6. Efficacy and persistence between dimethyl fumarate, fingolimod, and ocrelizumab after natalizumab cessation

Author

Macdonell, R., Zhu, C., Kalincik, T., Horakova, D., Zhen, Z., Buzzard, K., Skibina, O., Alroughani, R., Izquierdo, G., Eichau, S., Kuhle, J., Patti, F., Grand'Maison, F., Hodgkinson, S., Grammond, P., Lechner-Scott, J., Butler, E., Prat, A., Girard, M., Butzkueven, H., Van der Walt, A., Merlo, D., Monif, M., Jokubaitis, V., Khoury, S. J., Yamout, B., Garber, J., Kermode, A., Van Hijfte, L., Laureys, G., Boz, C., Terzi, M., Prevost, J., Gerlach, O., Van Wijmeersch, B., Barnett, M., Van Pesch, V., Sa, M. Jose, Slee, M., Ozakbas, S., Weinstock-Guttman, B., and Duquette, P.

Published
2022

7. A non-inferiority study of rituximab versus ocrelizumab in relapsing-remitting multiple sclerosis

Author

Skibina, O., Msbase and Danish Sclerosis Registry Study Grp, Msbase and Danish Sclerosis Registry Study Grp, Kalincik, T., Magyari, M., Gray, O., Sellebjerg, F., Soysal, A., Grand'Maison, F., Grammond, P., John, N., Van Hijfte, L., Laureys, G., Terzi, M., Kuhle, J., Lechner-Scott, J., Butzkueven, H., Van der Walt, A., Buzzard, K., Ozakbas, S., Alroughani, R., Boz, C., MacDonnell, G., Hughes, S., and Roos, I.

Published
2022

8. Real-World Comparative Effectiveness and Persistence of Cladribine Tablets and Other Oral Disease-Modifying Treatments for Multiple Sclerosis from GLIMPSE: Results from the MSBase Registry

Author

Spitaleri, D., Kuhle, J., Ozakbas, SERKAN, Patti, F., Ampapa, R., Horakova, D., Soysal, A., Butzkueven, H., Spelman, T., Lechner-Scott, J., Yamout, B., Alroughani, R., Terzi, M., Hodgkinson, S., Sanchez-Menoyo, J., Blanco, Y., Van Pesch, V., Van der Walt, A., Kalincik, T., Laureys, G., Wong, S., Tundia, N., Altintas, A., Oh, J., Gerlach, O., Al-Asmi, A., and Macdonell, R.

Published
2022

9. Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression (vol 208, 106180, 2021)

Author

De Brouwer, E, Becker, T, Moreau, Y, Havrdova, EK, Trojano, M, Eichau, S, Ozakbas, S, Onofrj, M, Grammond, P, Kuhle, J, Kappos, L, Sola, P, Cartechini, E, Lechner-Scott, J, Alroughani, R, Gerlach, O, Kalincik, T, Granella, F, Grand'Maison, F, Bergamaschi, R, Sa, MJ, Van Wijmeersch, B, Soysal, A, Sanchez-Menoyo, JL, Solaro, C, Boz, C, Iuliano, G, Buzzard, K, Aguera-Morales, E, Terzi, M, Trivio, TC, Spitaleri, D, Van Pesch, V, Shaygannejad, V, Moore, F, Oreja-Guevara, C, Maimone, D, Gouider, R, Csepany, T, Ramo-Tello, C, and Peeters, L

Published
2022

10. Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials

Author

Hardmeier, M., Schlaeger, R., Lascano, A. M., Toffolet, L., Schindler, C., Gobbi, C., Lalive, P., Kuhle, J., Kappos, L., and Fuhr, P.

Subjects
Disability Evaluation, Multiple Sclerosis, Neurology, Physiology (medical), Disease Progression, Humans, Neurology (clinical), Multiple Sclerosis, Chronic Progressive, Prognosis, Evoked Potentials, Sensory Systems, Biomarkers
Abstract

OBJECTIVE: To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities. METHODS: Thirty-nine patients with PPMS (expanded disability status scale (EDSS): 2.0-6.5; mean clinical follow-up: 2.8 years) had visual (VEP), upper and lower limb somatosensory (SEP) and motor EP (MEP) at baseline. Quantitative EP-scores for single (qVEP, qSEP, qMEP) and combined modalities were correlated to EDSS and compared to previously published data of 21 PPMS patients. Predictors of EDSS-change were analyzed in pooled data by linear regression. RESULTS: Samples were comparable. Except qVEP, all EP-scores were correlated to EDSS at baseline (Rho: 0.45-0.69; p < 0.01) and follow-up (Rho: 0.59-0.80; p < 0.001). Combined EP-modalities significantly predicted EDSS-change (R(2)adj: 0.24), while EDSS and age did not. Tibial qSEP (R(2)adj: 0.22) and qMEP (R(2)adj: 0.26) were the best single modality predictors, outperformed by their combination (R(2)adj: 0.32). CONCLUSIONS: Quantitative EP-scores predict up to 32% of EDSS-change over three years. Modalities representing motor and long tract function carry the main prognostic information. SIGNIFICANCE: Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS.

Published
2021

11. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author

Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, van Pesch, V, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, Albert, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, Teunissen, Charlotte E, Universitat Autònoma de Barcelona, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Basic (bio-) Medical Sciences, Ayşe, Altıntaş, Leurs, C.E., Twaalfhoven, H.A.M., Lissenberg-Witte, B.I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L.M., Alvarez-Cermeño, J.C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L.M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Rejdak, K., Frederiksen, J.L., Pihl-Jensen, G., Jensen, P.E.H., Khalil, M., Voortman, M.M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B.M.J., Killestein, J., Bridel, C., Teunissen, C., School of Medicine, Department of Neurology, Neurology, Laboratory Medicine, Epidemiology and Data Science, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Department of Anatomy and Neurosciences [Amsterdam, The Netherlands] (Amsterdam Neuroscience), Section Clinical Neuroanatomy [Amsterdam, The Netherlands], VU University Medical Center [Amsterdam]-VU University Medical Center [Amsterdam], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Cliniques Universitaires Saint-Luc [Bruxelles], Clinical Centre of Serbia, Università degli Studi di Ferrara (UniFE), University Hospital Basel [Basel], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Red Española de Esclerosis Múltiple (REEM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Neurology, Medical University of Innsbruck, Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'Esclerosi Múltiple de Catalunya (CemCat), Vall d'Hebron University Hospital [Barcelona], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Szeged [Szeged], Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Koç University, Medical University of Lublin, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Danish Multiple Sclerosis Research Centre, Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Department of Neurology, AZ Sint Jan Brugge Oostende, Neuroscience Amsterdam, VU University Medical Centre, 1081HV 1117, Amsterdam, Amsterdam Neuroscience [Pays-Bas], and Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam]

Subjects
KFLC (kappa free light chain), Adult, Male, Multiple Sclerosis, Clinical Neurology, Esclerosi múltiple, CSF, CSF (cerebrospinal fluid), Immunoglobulin light chain, Sensitivity and Specificity, NO, Multiple sclerosis, Immunoglobulin kappa-Chains, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Immunoglobulin lambda-Chains, Humans, Medicine, Diagnostic biomarker, biomarkers, KFLC, OCB, 030304 developmental biology, 0303 health sciences, business.industry, Biochemical markers, Oligoclonal Bands, Reproducibility of Results, Middle Aged, OCB (oligoclonal IgG band), Free Light Chain, Biomarkers, Neurology, Multicenter study, Marcadors bioquímics, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Original Research Papers, 030217 neurology & neurosurgery, Kappa
Abstract

Objective: to validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: we performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: the cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS., NA

Published
2020

12. Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis

Author

Maggi P, Kuhle J, Schädelin S, van der Meer F, Weigel M, Galbusera R, Mathias A, Lu PJ, Rahmanzadeh R, Benkert P, La Rosa F, Bach Cuadra M., Bach Cuadra M, Sati P, Théaudin M, Pot C, van Pesch V, Leppert D, Stadelmann C, Kappos L, Du Pasquier R, Reich DS, Absinta M, and Granziera C

Abstract

Objective:To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage. Methods:In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases. Results:In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68;p< 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4;p= 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (βadd, 16.3; 95% confidence interval [CI], 4.6-28.0;p< 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; βadd, 30.4; 95% CI, 15.6-45.2;p< 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (βadd, 1.1; 95% CI, 0.3-1.9;p< 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center:p= 0.004 andp= 0.0002, respectively). Conclusion:Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.

Published
2021

13. Serum neurofilament light and tau as markers for overall mortality in the elderly general population – an analysis from the MEMO cohort study

Author

Rübsamen, N, Maceski, A, Leppert, D, Kuhle, J, Peters, A, Karch, A, and Berger, K

Subjects
SIMOA, ddc: 610, nervous system, biomarker, prognosis, tau, neurofilament, 610 Medical sciences, Medicine, mortality
Abstract

Background: Neurofilament light (NfL) is assumed to be released from dying neurons. Detection of NfL in serum is a quantitative measure of neuro-axonal injury. Tau, a microtubule-associated protein in neurons, is complementary to NfL because of its strong association with the process of overall brain[for full text, please go to the a.m. URL], 65th Annual Meeting of the German Association for Medical Informatics, Biometry and Epidemiology (GMDS), Meeting of the Central European Network (CEN: German Region, Austro-Swiss Region and Polish Region) of the International Biometric Society (IBS)

Published
2021
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14. Cortical lesion detection using FLAWS in multiple sclerosis

Author

Muller, J., Rahmanzadeh, R., Tsagkas, C., Barakovic, M., Lu, P. -J., Yaldizli, O., Weigel, M., Beaumont, J., La Rosa, F., Cuadra, M. Bach, Kappos, L., Kuhle, J., Gambarota, G., Granziera, C., Jonchère, Laurent, University Hospital Basel [Basel], Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne (UNIL), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lausanne = University of Lausanne (UNIL)

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Meeting Abstract

Published
2021

15. Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

Author

Schindler, P., Grittner, U., Oechtering, J., Leppert, D., Siebert, N., Duchow, A.S., Oertel, F.C., Asseyer, S., Kuchling, J., Zimmermann, H.G., Brandt, A.U., Benkert, P., Reindl, M., Jarius, S., Paul, F., Bellmann-Strobl, J., Kuhle, J., and Ruprecht, K.

Subjects
Adult, Male, Serum, Research, Neuromyelitis Optica, Aquaporin-4 immunoglobulin G, Biomarker, Middle Aged, Prognosis, Glial fibrillary acidic protein, Severity of Illness Index, Neurofilament light chain protein, Neuromyelitis optica spectrum disorder, Neurofilament Proteins, Humans, Female, Myelin oligodendrocyte glycoprotein immunoglobulin G, Neurology. Diseases of the nervous system, Function and Dysfunction of the Nervous System, RC346-429, Biomarkers, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Aged, Autoantibodies
Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG(+)) NMOSD. Methods: sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG(+) patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG(+)) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG(+) patients over a median observation period of 4.25 years. Results: In patients with AQP4-IgG(+) NMOSD, median sGFAP (109.2 pg/ml) was non-significantly higher than in MOG-IgG(+) patients (81.1 pg/ml; p = 0.83) and healthy controls (67.7 pg/ml; p = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG(+), but not MOG-IgG(+) patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30, p = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = - 1.28, p = 0.01). While in AQP4-IgG(+), but not MOG-IgG(+) patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24, p = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09, p = 0.15) and MSFC (standardized effect size = - 1.75, p = 0.06) in patients with AQP4-IgG(+) NMOSD. Patients with AQP4-IgG(+) NMOSD with sGFAP > 90 pg/ml at baseline had a shorter time to a future attack than those with sGFAP

Published
2021

16. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

Author

Disanto, G1, Adiutori, R2, Dobson, R2, Martinelli, V3, Dalla Costa G3, Runia, T4, Evdoshenko, E5, Thouvenot, E6, Trojano, M7, Norgren, N8, Teunissen, C9, Kappos, L10, Giovannoni, G2, Kuhle, J, Bianchi, L, Topping, J, Bestwick, Jp, Meier, Uc, Lazareva, N, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, Jc, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, Ad, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, Km, Galimberti, D, Rejdak, K, Lycke, J, Frederiksen, Jl, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rl, Yaldizli, Ö, Vécsei, L, Kieseier, Bc, Hartung, Hp, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, Lm, Leone, M, Barizzone, N, Deisenhammer, F, Montalban, X, Tintoré, M, Olsson, T, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Furlan, R, Comi, G, Ramagopalan, Sv., Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratory Medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, Disanto, G., Adiutori, R., Dobson, R., Martinelli, V., Dalla Costa, G., Runia, T., Evdoshenko, E., Thouvenot, E., Trojano, M., Norgren, N., Teunissen, C., Kappos, L., Giovannoni, G., Kuhle, J., on behalf of the International ClinicallyIsolated Syndrome Study, Group, and Neurology

Subjects
Male, Pathology, Future studies, Gastroenterology, 0302 clinical medicine, Neurofilament Proteins, Multiple Sclerosi, 0303 health sciences, Clinically isolated syndrome, medicine.diagnostic_test, Medicine (all), Neurofilament Protein, Demyelinating Disease, Magnetic Resonance Imaging, Psychiatry and Mental Health, Predictive value of tests, Disease Progression, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, Neurofilament light, multiple sclerosis, adult, axons, biomarkers, demyelinating diseases, disease progression, female, follow-up studies, humans, magnetic resonance imaging, male, neurofilament proteins, predictive value of tests, neurology (clinical), psychiatry and mental health, surgery, arts and humanities (miscellaneous), medicine (all), [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Axon, Follow-Up Studie, 03 medical and health sciences, Arts and Humanities (miscellaneous), Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, MULTIPLE SCLEROSIS, 030304 developmental biology, business.industry, Multiple sclerosis, Magnetic resonance imaging, Biomarker, medicine.disease, Axons, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Demyelinating Diseases, Follow-Up Studies
Abstract

International audience; BACKGROUND:Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls.METHODS:We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3-7.9)); and 92 healthy controls.RESULTS:NfL levels were higher in FC (24.1 pg/mL (13.5-51.8)) and NC (19.3 pg/mL (13.6-35.2)) than in healthy controls (7.9 pg/mL (5.6-17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p = 1.5 × 10(-5) and OR = 7.03; 95% CI 2.85 to 17.34; p = 2.3 × 10(-5), respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR = 2.36; 95% CI 1.21 to 4.59; p = 0.011), gadolinium-enhancing lesions (OR = 2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR = 2.54; 95% CI 1.21 to 5.31; p = 0.013) at CIS diagnosis.CONCLUSIONS:If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.

Published
2016

17. Elevated Lipoprotein(a) in Perinatally HIV-Infected Children Compared with Healthy Ethnicity-Matched Controls

Author

Van Den Hof, Malon, Haneveld, Mirthe J.Klein, Blokhuis, Charlotte, Scherpbier, Henriette J., Jansen, Hans P.G., Kootstra, N. A., Dallinga-Thie, Geesje M., Van Deventer, Sander J.H., Tsimikas, Sotirios, Pajkrt, Dasja, Van Den Hof, M., Blokhuis, C., Cohen, S., Pajkrt, D., Kuijpers, T. W., Van Der Plas, A., Weijsenfeld, A., Ter Stege, J. S., Caan, M. W.A., Mutsaerts, H. J.M.M., Majoie, C. B.L.M., Demirkaya, N., Verbraak, F. D., Schmand, B., Geurtsen, G., Mathot, R. A.A., Wit, F. W.N.M., Reiss, P., Teunissen, C. E., Kuhle, J., Meijer, J. C.M., Pediatric surgery, Amsterdam Reproduction & Development (AR&D), APH - Aging & Later Life, Ophthalmology, Clinical chemistry, and ACS - Atherosclerosis & ischemic syndromes

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

Background: HIV-associated cardiovascular disease (CVD) risk in combination antiretroviral therapy (cART)-treated perinatally HIV-infected patients (PHIV+) remains unknown due to the young age of this population. Lipoprotein(a) (Lp(a)) has been established as an independent causal risk factor for CVD in the general population but has not been well established in the population of PHIV+. Methods: We cross-sectionally compared lipid profiles, including nonfasting Lp(a), together with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides between 35 cART-treated PHIV+ children aged 8-18 years and 37 controls who were matched for age, sex, ethnicity, and socioeconomic status. We explored associations between Lp(a) and disease-and treatment-related factors (inflammation, monocyte activation, and vascular), biomarkers, and neuroimaging outcomes using linear regression models. Results: PHIV+ children had significantly higher levels of Lp(a) compared with controls (median, 43.6 [21.6-82.4] vs 21.8 [16.8-46.6] mg/dL; P =. 033). Other lipid levels were comparable between groups. Additional assessment of apolipoprotein B, apolipoprotein CIII, apolipoprotein E, and APOE genotype revealed no significant differences. Higher Lp(a) levels were associated with higher plasma apoB levels and with lower monocyte chemoattractant protein-1 and TG levels in PHIV+ children. Lp(a) was not associated with HIV-or cART-related variables or with neuroimaging outcomes. Conclusions: cART-treated PHIV+ children appear to have higher levels of Lp(a) compared with ethnicity-matched controls, which may implicate higher CVD risk in this population. Future research should focus on the association between Lp(a) and (sub)clinical CVD measurements in cART-treated PHIV+ patients. Dutch Trial Register number: NRT4074.

Published
2019

19. Elevated Lipoprotein(a) in Perinatally HIV-Infected Children Compared With Healthy Ethnicity-Matched Controls

Author

Hof, M. van den, Haneveld, M.J.K., Blokhuis, C., Scherpbier, H.J., Jansen, H.P.G., Kootstra, N.A., Dallinga-Thie, G.M., Deventer, S.J.H. van, Tsimikas, S., Pajkre, D., Cohen, S., Kuijpers, T.W., Plas, A. van der, Weijsenfeld, A., Stege, J.S. ter, Caan, M.W.A., Mutsaerts, H.J.M.M., Majoie, C.B.L.M., Deinirkaya, N., Verbraak, F.D., Schmand, B., Geurtsen, G., Mathot, R.A.A., Wit, F.W.N.M., Reiss, P., Teunissen, C.F., Kuhle, J., Meijer, J.C.M., and NOVICE Study Grp

Subjects
lipids, lipoprotein(a), lipids (amino acids, peptides, and proteins), perinatal HIV infection, cardiovascular disease risk, MRI
Abstract

Background. HIV-associated cardiovascular disease (CVD) risk in combination antiretroviral therapy (cART)-treated perinatally HIV-infected patients (PHIV+) remains unknown due to the young age of this population. Lipoprotein(a) (Lp(a)) has been established as an independent causal risk factor for CVD in the general population but has not been well established in the population of PHIV+.Methods. We cross-sectionally compared lipid profiles, including nonfasting Lp(a), together with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides between 35 cART-treated PHIV+ children aged 8-18 years and 37 controls who were matched for age, sex, ethnicity, and socioeconomic status. We explored associations between Lp(a) and disease- and treatment-related factors (inflammation, monocyte activation, and vascular), biomarkers, and neuroimaging outcomes using linear regression models.Results. PHIV+ children had significantly higher levels of Lp(a) compared with controls (median, 43.6 [21.6-82.4] vs 21.8 [16.8-46.6] mg/dL; P = .033). Other lipid levels were comparable between groups. Additional assessment of apolipoprotein B, apolipoprotein CIII, apolipoprotein E, and APOE genotype revealed no significant differences. Higher Lp(a) levels were associated with higher plasma apoB levels and with lower monocyte chemoattractant protein-1 and TG levels in PHIV+ children. Lp(a) was not associated with HIV- or cART-related variables or with neuroimaging outcomes.Conclusions. cART-treated PHIV+ children appear to have higher levels of Lp(a) compared with ethnicity-matched controls, which may implicate higher CVD risk in this population. Future research should focus on the association between Lp(a) and (sub) clinical CVD measurements in cART-treated PHIV+ patients.

Published
2019

20. Real-world experience with Ocrelizumab in the MSBase Registry

Author

Patti, F., Eichau, S., Alroughani, R., Terzi, M., Boz, C., Grand'Maison, F., Grammond, P., Kalincik, T., Van Pesch, V., Barnett, M., Kuhle, J., Hodgkinson, S., Skibina, O., Soysal, A., Butler, E., Slee, M., Prevost, J., Laureys, G., Macdonell, R., van Beek, J., Craveiro, L., Wormser, D., Muros-Le Rouzic, E., Lechner-Scott, J., Ozakbas, SERKAN, Butzkueven, H., and Spelman, T.

Published
2019

21. Elevated Lipoprotein(a) in Perinatally HIV-Infected Children Compared with Healthy Ethnicity-Matched Controls

Author

van den Hof, Malon, Haneveld, Mirthe J. Klein, Blokhuis, Charlotte, Scherpbier, Henriette J., Jansen, Hans P. G., Kootstra, Neeltje A., Dallinga-Thie, Geesje M., van Deventer, Sander J. H., Tsimikas, Sotirios, Pajkrt, Dasja, van den Hof, M., Blokhuis, C., Cohen, S., Pajkrt, D., Scherpbier, H. J., Kuijpers, T. W., van der Plas, A., Weijsenfeld, A., ter Stege, J. S., Kootstra, N. A., Caan, M. W. A., Mutsaerts, H. J. M. M., Majoie, C. B. L. M., Verbraak, F. D., Schmand, B., Geurtsen, G., Mathot, R. A. A., Wit, F. W. N. M., Reiss, P., Teunissen, C. E., Kuhle, J., Meijer, J. C. M., Paediatric Infectious Diseases / Rheumatology / Immunology, APH - Aging & Later Life, AII - Infectious diseases, Graduate School, ARD - Amsterdam Reproduction and Development, APH - Quality of Care, APH - Personalized Medicine, Paediatric Pulmonology, General Paediatrics, Experimental Immunology, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Biomedical Engineering and Physics, Radiology and Nuclear Medicine, ACS - Microcirculation, Pharmacy, Global Health, APH - Methodology, APH - Societal Participation & Health, APH - Mental Health, and ACS - Pulmonary hypertension & thrombosis

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

Background: HIV-associated cardiovascular disease (CVD) risk in combination antiretroviral therapy (cART)-treated perinatally HIV-infected patients (PHIV+) remains unknown due to the young age of this population. Lipoprotein(a) (Lp(a)) has been established as an independent causal risk factor for CVD in the general population but has not been well established in the population of PHIV+. Methods: We cross-sectionally compared lipid profiles, including nonfasting Lp(a), together with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides between 35 cART-treated PHIV+ children aged 8-18 years and 37 controls who were matched for age, sex, ethnicity, and socioeconomic status. We explored associations between Lp(a) and disease-and treatment-related factors (inflammation, monocyte activation, and vascular), biomarkers, and neuroimaging outcomes using linear regression models. Results: PHIV+ children had significantly higher levels of Lp(a) compared with controls (median, 43.6 [21.6-82.4] vs 21.8 [16.8-46.6] mg/dL; P =. 033). Other lipid levels were comparable between groups. Additional assessment of apolipoprotein B, apolipoprotein CIII, apolipoprotein E, and APOE genotype revealed no significant differences. Higher Lp(a) levels were associated with higher plasma apoB levels and with lower monocyte chemoattractant protein-1 and TG levels in PHIV+ children. Lp(a) was not associated with HIV-or cART-related variables or with neuroimaging outcomes. Conclusions: cART-treated PHIV+ children appear to have higher levels of Lp(a) compared with ethnicity-matched controls, which may implicate higher CVD risk in this population. Future research should focus on the association between Lp(a) and (sub)clinical CVD measurements in cART-treated PHIV+ patients. Dutch Trial Register number: NRT4074.

Published
2019

22. Introducing Machine Learning for full MS patient trajectories improves predictions for disability score progression

Author

Brouwer, E., Peeters, L., Becker, T., Altintas, A., Soysal, A., Wijmeersch, B., Boz, C., Oreja-Guevara, C., Gobbi, C., Solaro, C., Ramo, C., Spitaleri, D. L., Maimone, D., Aguera-Morales, E., Cartechini, E., Butler, E., Havrdova, E., Patti, F., Granella, F., Grand Maison, F., Moore, F., Verheul, F., Iuliano, G., Butzkueven, H., Lechner-Scott, J., Kuhle, J., Sanchez Menoyo, J. L., Rojas, J. I., Prevost, J., Onofrj, M., Rio, M. E., Sa, M. J., Saladino, M. L., Slee, M., Barnett, M., Terzi, M., Deri, N., Mccombe, P., Sola, P., Duquette, P., Grammond, P., Ampapa, R., Alroughani, R., Hupperts, R., Recai Turkoglu, Gouider, R., Fernandez Bolanos, R., Bergamaschi, R., Kalincik, T., and Moreau, Y.

Published
2019

23. Neurofilament light chain: a biomarker for disease onset and survival in genetic frontotemporal dementia

Author

Meeter, L., Dopper, E., Jiskoot, L., Sanchez-Valle, R., Caroline Graff, Benussi, L., Ghidoni, R., Pijnenburg, Y., Borroni, B., Galimberti, D., Laforce, R. J., Masellis, M., Vandenberghe, R., Le Ber, I., Otto, M., Minkelen, R., Papma, J., Rombouts, S., Balasa, M., Oijerstedt, L., Jelic, V., Cash, D., Harding, S., Cardoso, M. J., Ourselin, S., Dick, K., Rossor, M., Binetti, G., Padovani, A., Scarpini, E., Fenoglio, C., Tartaglia, C., Lamari, F., Barro, C., Kuhle, J., Rohrer, J., Teunissen, C., and Swieten, J.

Published
2016

24. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

Author

Disanto, G, Adiutori, R, Dobson, R, Martinelli, V, Costa, GD, Runia, T, Evdoshenko, E, Thouvenot, E, Trojano, M, Norgren, N, Teunissen, C, Kappos, L, Giovannoni, G, Kuhle, J, Bianchi, L, Topping, J, Bestwick, JP, Meier, UC, Lazareva, N, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeno, JC, Kleinova, P, Horakova, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martinez, AD, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, O, Myhr, K, Galimberti, D, Rejdak, K, Lycke, J, Frederiksen, JL, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, RL, Yaldizli, O, Vecsei, L, Kieseier, BC, Hartung, HP, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdova, E, Villar, LM, Leone, M, Barizzone, N, Deisenhammer, F, Montalban, X, Tintore, M, Olsson, T, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Furlan, R, Comi, G, Ramagopalan, SV, and Int Clinically Isolated Syndrome S

Abstract

Background Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls. Methods We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3-7.9)); and 92 healthy controls. Results NfL levels were higher in FC (24.1 pg/mL (13.5-51.8)) and NC (19.3 pg/mL (13.6-35.2)) than in healthy controls (7.9 pg/mL (5.6-17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p=1.5x10(-5) and OR=7.03; 95% CI 2.85 to 17.34; p=2.3x10(-5), respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR=2.36; 95% CI 1.21 to 4.59; p=0.011), gadolinium-enhancing lesions (OR=2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR=2.54; 95% CI 1.21 to 5.31; p=0.013) at CIS diagnosis. Conclusions If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.

Published
2016

27. Neurofilament ELISA validation

Author

Petzold, A. Altintas, A. Andreoni, L. Bartos, A. Berthele, A. Blankenstein, M.A. Buee, L. Castellazzi, M. Cepok, S. Comabella, M. Constantinescu, C.S. Deisenhammer, F. Deniz, G. Erten, G. Espiño, M. Fainardi, E. Franciotta, D. Freedman, M.S. Giedraitis, V. Gilhus, N.E. Giovannoni, G. Glabinski, A. Grieb, P. Hartung, H.-P. Hemmer, B. Herukka, S.-K. Hintzen, R. Ingelsson, M. Jackson, S. Jacobsen, S. Jafari, N. Jalosinski, M. Jarius, S. Kapaki, E. Kieseier, B.C. Koel-Simmelink, M.J.A. Kornhuber, J. Kuhle, J. Kurzepa, J. Lalive, P.H. Lannfelt, L. Lehmensiek, V. Lewczuk, P. Livrea, P. Marnetto, F. Martino, D. Menge, T. Norgren, N. Papuć, E. Paraskevas, G.P. Pirttilä, T. Rajda, C. Rejdak, K. Ricny, J. Ripova, D. Rosengren, L. Ruggieri, M. Schraen, S. Shaw, G. Sindic, C. Siva, A. Stigbrand, T. Stonebridge, I. Topcular, B. Trojano, M. Tumani, H. Twaalfhoven, H.A.M. Vécsei, L. Van Pesch, V. Vanderstichele, H. Vedeler, C. Verbeek, M.M. Villar, L.M. Weissert, R. Wildemann, B. Yang, C. Yao, K. Teunissen, C.E.

Abstract

Background: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. Methods: The UmanDiagnostics NF-light ®enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68 kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. Results: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R = 0.60, p < 0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R = 0.98, p < 0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. Conclusion: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online. © 2009 Elsevier B.V.

Published
2010

28. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results

Author

Comi, G, O'Connor, P, Montalban, X, Antel, J, Radue, Ew, Karlsson, G, Pohlmann, H, Aradhye, S, Kappos, L, Easton, Jd, Kesselring, J, Weinshenker, Bg, Laupacis, A, Zarbin, M, Calandra, T, Temkin, N, Dimarco, J, Hudson, Ld, Durcan, L, Bar Or, A, Duquette, P, Bernier, G, Freedman, M, Maclean, H, Costello, F, Gray, Ta, Hohol, M, Devonshire, V, Oger, J, Hashimoto, S, Sørensen, Ps, Datta, P, Faber Rod JC, Frederiksen, J, Knudsen, S, Petrenaite, V, Färkkila, M, Harno, H, Halavaara, J, Elovaara, I, Kuusisto, H, Palmio, J, Airas, L, Kaasinen, V, Laaksonen, M, Vermersch, P, Pelletier, J, Feuillet, L, Suchet, L, Mauch, E, Gunser, C, Oberbeck, K, Rieckmann, P, Buttmann, M, Klein, M, Ghezzi, A, Zaffaroni, M, Baldini, S, Mancardi, G, Cioli, F, Capello, E, Rodegher, M, Radaelli, M, Pozzilli, C, Onesti, Emanuela, Romano, Silvia, Czlonkowska, A, Litwin, T, Darda Ledzion, L, Kwiecinski, H, Golebiowski, M, Podlecka, A, Cunha, L, Sousa, L, Matias, F, Pedrosa, R, Almeida, M, Pena, Je, de Sá, J, Ferreira, J, Rosa, M, Arbizu, T, Carmona, O, Casado, V, Tintore, M, Pelayo, R, Arroyo, R, Bartolome, M, De las Heras, V, Casanova, B, Bosca, I, Fernandez, O, Leon, A, Romero, F, Izquierdo, G, Gamero, M, Garcia, Jm, Kuhle, J, Mehling, M, Achtnichts, L, Goebels, N, Skulina, C, Waskoenig, J, Bates, D, Nichols, P, Bendfeldt, K, de Vera, A, Gruenbauer, W., Ben Dahan, David, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oral, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Time Factors, Adolescent, Phases of clinical research, Administration, Oral, Kaplan-Meier Estimate, Relapsing-Remitting, administration /&/ dosage/adverse effects, Placebo, law.invention, Pulmonary function testing, 03 medical and health sciences, Disability Evaluation, Young Adult, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, law, Sphingosine, Internal medicine, Fingolimod Hydrochloride, administration /&/ dosage/adverse effects/analogs /&/ derivatives, medicine, Humans, Adverse effect, business.industry, Fingolimod, Magnetic Resonance Imaging, diagnosis/drug therapy/pathology, Administration, Oral, Adolescent, Adult, Disability Evaluation, Female, Humans, Immunosuppressive Agents, administration /&/ dosage/adverse effects, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Multiple Sclerosis, diagnosis/drug therapy/pathology, Propylene Glycols, administration /&/ dosage/adverse effects, Sphingosine, administration /&/ dosage/adverse effects/analogs /&/ derivatives, Time Factors, Treatment Outcome, Young Adult, 3. Good health, Surgery, Clinical trial, Treatment Outcome, Neurology, Propylene Glycols, 030220 oncology & carcinogenesis, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug
Abstract

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7—36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15—24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88—89%) or new T2 lesions (70—78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20—0.21, and 68—73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3—5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme.

Published
2010

29. A consensus protocol for the standardisation of cerebrospinal fluid collection and biobanking

Author

Teunissen, CE, Petzold, A, Bennett, JL, Berven, FS, Brundin, L, Comabella, M, Franciotta, D, Federiksen, JL, Fleming, JO, Furlan, R, Hintzen, Rogier, Hughes, SG, Johnson, MH, Krasulova, E, Kuhle, J, Magnone, MC, Rajda, C, Rejdak, K, Schmidt, HK, van Pesch, V, Waubant, E, Wolf, C, Giovannoni, G, Deisenhammer, F, Hegen, H, Hemmer, B, Tumani, HT, Molecular cell biology and Immunology, Neurology, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases

Abstract

There is a long history of research on body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only very few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of Studies owing to the lack of sufficient samples that call be obtained in sin-le-centre studies. Therefore, collaboration between investigators is needed to establish lame biobanks of well-defined samples. Standardised protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here. a consensus report on guidelines of CSF collection and biobanking is presented. formed by the European network for Biomarkers in MS for CSF biomarker research in Multiple sclerosis. In this paper, we FOCUS on CSF collection procedures, preanalytical factors, and high quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks For research targeting any neurological disease.

Published
2010

30. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study

Author

O'Connor, P, Comi, G, Montalban, X, Antel, J, Radue, Ew, de Vera, A, Pohlmann, H, Kappos, L, Easton, Jd, Kesselring, J, Weinshenker, Bg, Laupacis, A, Zarbin, M, Calandra, T, Temkin, N, Dimarco, J, Hudson, Ld, Durcan, L, Bar Or, A, Duquette, P, Bernier, G, Freedman, M, Maclean, H, Costello, F, Gray, Ta, Hohol, M, Devonshire, V, Hashimoto, S, Sørensen, Ps, Datta, P, Faber Rod JC, Frederiksen, J, Knudsen, S, Petrenaite, V, Harno, H, Färkkila, M, Halavaara, J, Elovaara, I, Kuusisto, H, Palmio, J, Airas, L, Kaasinen, V, Laaksonen, M, Vermersch, P, Pelletier, J, Feuillet, L, Suchet, L, Mauch, E, Gunser, C, Oberbeck, K, Rieckmann, P, Buttmann, M, Klein, M, Ghezzi, A, Zaffaroni, M, Baldini, S, Mancardi, G, Cioli, F, Capello, E, Rodegher, M, Radaelli, M, Pozzilli, C, Onesti, Emanuela, Romano, Silvia, Czlonkowska, A, Litwin, T, Darda Ledzion, L, Kwiecinski, H, Golebiowski, M, Podlecka, A, Nojszewska, K, Cunha, L, Sousa, L, Matias, F, Pedrosa, R, Almeida, M, Pena, Je, de Sá, J, Ferreira, J, Rosa, M, Arbizu, T, Carmona, O, Casado, V, Tintore, M, Pelayo, R, Arroyo, R, Bartolome, M, De las Heras, V, Casanova, B, Bosca, I, Fernandez, O, Leon, A, Romero, F, Izquierdo, G, Gamero, M, Garcia, Jm, Kuhle, J, Mehling, M, Achtnichts, L, Goebels, N, Skulina, C, Waskoenig, J, Bates, D, Nichols, P, Bendfeldt, K, Karlsson, G, Burtin, P, Zubal, T., Oconnor, P., Comi, G., Montalban, X., Antel, J., Radue, E. W., De Vera, A., Pohlmann, H., Kappos, L., and Radaelli, M

Subjects
Male, Time Factors, Administration, Oral, Kaplan-Meier Estimate, Gastroenterology, Severity of Illness Index, law.invention, Immunosuppressive Agent, Disability Evaluation, Randomized controlled trial, law, Oral administration, Sphingosine, hemic and lymphatic diseases, Multiple Sclerosi, administration /&/ dosage, Respiratory Function Test, Incidence, Middle Aged, Fingolimod, Propylene Glycol, Magnetic Resonance Imaging, Respiratory Function Tests, Tolerability, Administration, Female, Oral, Adolescent, Adult, Disability Evaluation, Double-Blind Method, Female, Humans, Immunosuppressive Agents, administration /&/ dosage, Incidence, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, drug therapy/mortality, Propylene Glycols, administration /&/ dosage, Respiratory Function Tests, methods, Severity of Illness Index, Sphingosine, administration /&/ dosage/analogs /&/ derivatives, Time Factors, Young Adult, medicine.symptom, Immunosuppressive Agents, medicine.drug, Human, Oral, Adult, medicine.medical_specialty, Multiple Sclerosis, Time Factor, Adolescent, Placebo, methods, Lesion, Young Adult, Double-Blind Method, Internal medicine, administration /&/ dosage/analogs /&/ derivatives, Severity of illness, medicine, drug therapy/mortality, Humans, business.industry, Fingolimod Hydrochloride, Surgery, Clinical trial, Propylene Glycols, Neurology (clinical), business
Abstract

Objective:: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS:: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS:: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS:: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity. © 2009 AAN Enterprises, Inc.

Published
2009

31. Health-related quality of life in multiple sclerosis: Effects of natalizumab

Author

Rudick, R. A., Miller, D., Hass, S., Hutchinson, M, Calabresi, P. A., Confavreux, C., Galetta, S. L., Giovannoni, G., Havrdova, E., Kappos, L., Lublin, F. D., Miller, D. H., O'Connor, P. W., Phillips, J. T., Polman, C. H., Radue, Ew, Stuart, W. H., Wajgt, A., Weinstock Guttman, B., Wynn, D. R., Lynn, F., Panzara, M. A., Affirm, Macdonell, SENTINEL Investigators including: R., Hughes, A., Taylor, I., Lee, Y. C., Ma, H., King, J., Kilpatrick, T., Butzkueven, H., Marriott, M., Pollard, J., Spring, P., Spies, J., Barnett, M., Dehaene, I., Vanopdenbosch, L., D’Hooghe, M., Van Zandijcke, M., Derijck, O., Seeldrayers, P., Jacquy, J., Piette, T., De Cock, C., Medaer, R., Soors, P., Vanroose, E., Vanderhoven, L., Nagels, G., Dubois, B., Deville, M. C., D’Haene, R., Jacques, F., Hallé, D., Gagnon, S., Likavcan, E., Murray, T. J., Bhan, V., Mackelvey, R., Maxner, C. E., Christie, S., Giaccone, R., Guzman, D. A., Melanson, M., Esfahani, F., Gomori, A. J., Nagaria, M. H., Grand’Maison, F., Berger, L., Nasreddine, Z., Duplessis, M., Brunet, D., Jackson, A., Pari, G., O’Connor, P., Gray, T., Hohol, M., Marchetti, P., Lee, L., Murray, B., Sahlas, J., Perry, J., Devonshire, V., Hooge, J., Hashimoto, S., Oger, J., Smyth, P., Rice, G., Kremenchutzky, M., Stourac, P., Kadanka, Z., Benesova, Y., Niedermayerova, I., Meluzinova, E., Marusic, P., M, Bojar, Zarubova, K., Houzvicková, E., Piková, J., Talab, R., Faculty, Hospital Olomouc, Olomouc, B. Muchova, Urbánek, K, Kettnerova, Z., Mares, J., Otruba, P., Zapletalová, O., Hradilek, P., Ddolezil, D. Dolezil, Woznicova, I., Höfer, R., Ambler J. Fiedler, Z. Ambler J. Fiedler, Sucha, J., Matousek, V., Rektor, I., Dufek, M., Mikulik, R., Mastik, J., Tyrlikova, I., General, Teaching Hospital, Prague, E. Havrdová, Horakova, D., Kalistová, H., Týblová, M., Ehler, E., Novotná, A., Geier, P., Soelberg Sorensen, P., Ravnborg, M., Petersen, B., Blinkenberg, M., Färkkilä, M., Harno, H., Kallela, M., Häppölä, O., Elovaara, I., Kuusisto, H., Ukkonen, M., Peltola, J., Palmio, J., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Edan, G., Le Page, E., Mérienne, M., Yaouanq, J., Clanet, M., Mekies, C., Azais Vuillemin, C., Senard, A., Lau, G., Steinmetz, G., Warter V. Wolff, J. Warter V. Wolff, Fleury, M., Tranchant, C., Stark, E., Buckpesch Heberer, U., Henn, K. H., Skoberne, T., Schimrigk, S., Hellwig, K., Brune, N., Weiller, C., Gbadamosi, J., Röther, J., Heesen, C., Buhmann, C., Karageorgiou, C., Korakaki, D., Giannoulis, D. r., Tsiara, S., Thomaides, T., Thomopoulos, I., Papageorgiou, H., Armakola, F., Komoly, S., Rózsa, C., Matolcsi, J., Szabó, G. y., Molnár, B., Lovas, G., Dioszeghy, P., Szulics, P., Magyar, Z., Incze, J., Farkas, J., Clemens, B., Kánya, J., Valicskó, Z. s., Bense, E., Nagy, Z. s., Geréby, G., Perényi, J., Simon, Z. s., Szapper, M., Gedeon, L., Csanyi, A., Rum, G., Lipóth, S., Szegedi, A., Jávor, L., Nagy, I., Adám, I., Szirmai, I., Simó, M., Ertsey, C., I, Amrein, Kamondi, A., Harcos, P., Dobos, E., Szabó, B., Balas, V., Guseo, A., Fodor, E., Jófejü, E., Eizler, K., Csiba, L., Csépány, T., Pallagi, E., Bereczki, D., Jakab, G., Juhász, M., Bszabó, B. Szabó I. Mayer, Katona, G., Hutchinson, M., O’Dwyer, J., O’Rourke, K., Sanders, E. A. C. M., Rijk van Andel, J. F., Bomhof, M. A. M., van Erven, P., Hintzen I. Hoppenbrouwers, R. Q. Hintzen I. Hoppenbrouwers, Neuteboom, R. F., Zemel, D., van Doorn, P. A., Jacobs, B. C., Munster, E. T. h. L. Van, ter Bruggen, J. P., Bernsen, R., Jongen, P. J. H., de Smet, E. A. A., Tacken, H. F. H., Polman, C., Zwemmer, J., Nielsen, J., Kalkers, N., Kragt, J., Jasperse, B., Willoughby, E., Anderson, N. E., Barber, A., Anderson, T., Parkin, P. J., Fink, J., Avery, S., Mason, D., Kwiecinski, H., Zakrzewska Pniewska, B., Kaminska, A., Podlecka, A., Nojszewska, M., Czlonkowska, A., Zaborski, J., Wicha, W., Kruszewska Ozimowska, J., Darda Ledzion, L., Selmaj, K., Mochecka Thoelke, A., Pentela Nowicka, J., Walczak, A., Stasiolek, M., Stelmasiak, Z., Bartosik Psujek, H., Mitosek Szewczyk, K., Belniak, E., Chyrchel, U., Maciejowski, M., Strzyzewska Lubos, L., Lubos, L., Matusik, E., Maciejek, Z., Niezgodzinska Maciejek, A., Sobczynska, D., Slotala, T., Wawrzyniak, S., Kochanowicz K. Kuczynski, J. Kochanowicz K. Kuczynski, Zimnoch, R., Pryszmont, M., Drozdowski, W., Baniukiewicz, E., Kulakowska, A., Borowik, H., Lewonowska, M., Szczudlik, A., Róg, T., Gryz Kurek, E., Pankiewicz, J., Furgal, J., Kimkowicz, A., Fryze, W., Wierbicki, T., Michalak, L., Kowalewska, J., Swiatkiewicz, J., Hillert, J., Åkesson, E, Fredrikson, S., Diener, P, Olsson, T., Wallström, E., Fpiehl, F. Piehl L. Hopia, Brundin, L., Marta, M., Andersson, M., Lycke, J., Runmarker, B., Malmeström, C., Vaghfeldt, P., Skoog, B., Schluep, M., Bogousslavskyr, J., Du Pasquier, R., Achtnichts, L., Kuhle, J., Buitrago Telez, C., Schläger, R., Naegelin, Y., Eraksoy, M., Bebek, N., Akman Demir, G., Topcuoglu, B., Kurtuncu, M., Istanbul, University, Istanbul:, A. Siva, Saip, S., Altintas, A., Kiyat, A., Sharief, M., Kasti, M., Lim, E. T., Rashid, W., Silber, E., Saldanha, G., Hawkins, C., Mamutse, G., Woolmore, J., Hawkes, C., Findley, L., Dasilva, R., Gunasekara, H., Palace, J., Cader, Z., Littleton, E., Burke, G., Sharrack O. Suliman, B. Sharrack O. Suliman, Klaffke, S., Swash, M., Dhillon, H., Bates, D., Westwood, M., Nichol, P., Barnes, D., Wren, D., Stoy, N., Robertson, N., Pickersgill, T., Pearson, O., Lawthom, C., Young, C., Mills, R., Lecky, B., Ford, C., Katzman, J., Rosenberg, G., Cooper, J., Wrubel, B., Richardson, B., Lynch, S., Ridings, L., Mcvey, A., Nowack, W., Rae Grant, A., Mackin, G. A., Castaldo, J. E., Spikol, L. J., Carter, J., Wingerchuk, D., Caselli, R., Dodick, D., Scarberry, S., Bailly, R., Garnaas, K., Haake, B., Rossman, H., Belkin, M., Boudouris, W. D., Pierce, R. P., Mass, M., Yadav, V., Bourdette, D., Whitham, R. H., Heitzman, D., Martin, A., Greenfield, C. F., Agius, M., Richman, D. P., Vijayan, N., Wheelock, V. L., Reder, A., Arnason, B., Noronha, A., Balabanov, R., Ray, A., Sheremata, W., Delgado, S., Shebert, B., Maldonado, J., Bowen, J., Garden, G. A., Distad, B. J., Carrithers, M., Rizzo, M., Vollmer, T., Reiningerova, J., Guarnaccia, J., Lo, A., Richardson, G. B., Fazekas, F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, : D, Lampaert, J., Bartholome, E., Bier, J., Stenager, : E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Soelberg Sørensen, P., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, : J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, : T., Noblet, M., Rouaud, O., Couvreur, G., Lepage, E., Drapier, S., De Burghgraeve, V., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, : S., Grupe, A., Gutmann, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher E. Rothenfusser Körber, A. Steinbrecher E. Rothenfusser Körber, Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky, : O., Karusiss, D., Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, : C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, : C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Kragt, J. J., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fernandez Fernandez, : O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, : L., Wilmes, S., Karabudak, : R., Kurne, A., Erdem, S., Siva, A., Atamer, A., Bilgili, F., Topcular, B., Giovannoni, : G., Lava, : N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Boudoris, W., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Doherty, M., Wundes, A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Radue, E. W., de Vera, A., Bacelar, O., and Kuster, P.

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Visual analogue scale, Health Status, Population, Pain, Comorbidity, Placebo, Antibodies, law.invention, Natalizumab, Randomized controlled trial, Quality of life, Double-Blind Method, law, Internal medicine, Surveys and Questionnaires, Monoclonal, medicine, Prevalence, Humans, Longitudinal Studies, education, Humanized, education.field_of_study, Expanded Disability Status Scale, Neuroscience (all), business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Female, Patient Satisfaction, Treatment Outcome, United States, Quality of Life, Multiple sclerosis, medicine.disease, Neurology, Physical therapy, Neurology (clinical), business, medicine.drug
Abstract

Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007

Published
2007

33. Leman-PV as a clinical decision-support tool to assess MS activity: a multicentric longitudinal study at 1.5T and 3T MRI

Author

Todea, R. -A., Melie-Garcia, L., Barakovic, M., Siebenborn, N., Rahmanzadeh, R., Galbusera, R., Lu, P. -J., Weigel, M., Ruberte, E., Radue, E. W., Schadelin, S., Benkert, P., Yaldizli, O., Oechtering, J., Sinnecker, T., Mueller, S., Achtnichts, L., Vehoff, J., Disanto, G., Findling, O., Chan, A., Salmen, A., Pot, C., Lalive, P., Bridel, C., Zecca, C., Derfuss, T., Remonda, L., Wagner, F., Vargas, M. I., Du Pasquier, R., Pravata, E., Weber, J., Gobbi, C., Leppert, D., Wuerfel, J., Kober, T., Marechal, B., Corredor-Jerez, R., Psychogios, M. -N., Lieb, J., Kappos, L., Cuandra, M. Bach, Kuhle, J., and Granziera, C.

36. Multivariate clinically isolated syndrome (CIS) risk factor study: towards individual prognosis and treatment indication in CIS

Author

Kuhle, J., Dobson, R., Bestwick, J. P., Topping, J., Dalla Costa, G., Khademi, M., Sombekke, M., Killestein, J., Evdoshenko, E., Lazareva, N., Runia, T., Zbornikova, P., Horakova, D., D Alfonso, S., Thouvenot, E., Moll, N., Hegen, H., Rauch, S., Khalil, M., Fuchs, S., Lindberg, R. L. P., Derfuss, T., Sara Llufriu, Franciotta, D., Roesler, R., Lauda, F., Rajda, C., Drulovic, J., Menge, T., Kieseier, B. C., Avsar, T., Marignier, R., Malmestrom, C., Myhr, K. M., Wergeland, S., Annibali, V., Romano, S., Carra, A., Laroni, A., Frederiksen, J. L., Larsson, H. B., Uccelli, A., Martinez, A. D., Salvetti, M., Torkildsen, O., Lycke, J., Confavreux, C., Rejdak, K., Bosca, I., Brassat, D., Scarpini, E., Fenoglio, C., Galimberti, D., Siva, A., Hartung, H. P., Dujmovic, I., Vecsei, L., Tumani, H., Bergamaschi, R., Colombo, E., Villoslada, P., Saiz, A., Enzinger, C., Kappos, L., Deisenhammer, F., Alvarez-Cermeno, J. C., Villar, L., Pelletier, J., Lehmann, S., Castelnovo, G., Barizzone, N., Leone, M., Havrdova, E., Trojano, M., Iaffaldano, P., Direnzo, V., Comabella, M., Tintore, M., Montalban, X., Hintzen, R., Lapin, S., Teunissen, C., Piehl, F., Olsson, T., Furlan, R., Martinelli, V., Comi, G., Ramagopalan, S., and Giovannoni, G.

37. Comparison of the effectiveness of ocrelizumab vs interferons, fingolimod and natalizumab on relapses in relapsing-remitting multiple sclerosis

Author

Izanne Roos, Sharmin, S., Ozakbas, S., Horakova, D., Havrdova, E. K., Boz, C., Alroughani, R., Patti, F., Terzi, M., Lechner-Scott, J., Izquierdo, G., Eichau, S., Grammond, P., Buzzard, K., Skibina, O., Prat, A., Girard, M., Duquette, P., Soysal, A., Grand Maison, F., Kuhle, J., Walt, A., Butzkueven, H., Turkoglu, R., Butler, E., Laureys, G., Hijfte, L., Shaygannejad, V., Yamout, B., Khoury, S., Prevost, J., Sidhom, Y., Gouider, R., Cartechini, E., Sanchez-Menoyo, J. L., Sa, M. Jose, Macdonell, R., Pesch, V., Ramo-Tello, C., Mccombe, P., Willekens, B., Spitaleri, D., Ampapa, R., Al-Asmi, A., Slee, M., Besora, S., Malpas, C., and Kalincik, T.

45. Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes

Author

Todea R, Lu P, Fartaria M, Bonnier G, Du Pasquier R, Krueger G, Bach Cuadra M, Psychogios M, Kappos L, Kuhle J, and Cristina Granziera

Subjects
relapses, mri lesions, interferon beta-1a therapy, cortical lesions, serum neurofilamants, MP2RAGE, MRI, early relapsing remitting multiple sclerosis, scale, disability, Neurology, decreases, pathology, patterns, Neurology (clinical), mri, mp2rage, time
Abstract

Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes. Methods: Thirty-two RRMS patients (

50. Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: Results from MSBase registry

Author

Tim Spelman, Serkan Ozakbas, Raed Alroughani, Murat Terzi, Suzanne Hodgkinson, Guy Laureys, Tomas Kalincik, Anneke Van Der Walt, Bassem Yamout, Jeannette Lechner-Scott, Aysun Soysal, Jens Kuhle, Jose Luis Sanchez-Menoyo, Yolanda Blanco Morgado, Daniele LA Spitaleri, Vincent van Pesch, Dana Horakova, Radek Ampapa, Francesco Patti, Richard Macdonell, Abdullah Al-Asmi, Oliver Gerlach, Jiwon Oh, Ayse Altintas, Namita Tundia, Schiffon L Wong, Helmut Butzkueven, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Spelman, T., Ozakbas, S., Alroughani, R., Terzi, M., Hodgkinson, S., Laureys, G., Kalincik, T., Van Der Walt, A., Yamout, B., Lechner-Scott, J., Soysal, A., Kuhle, J., Sanchez-Menoyo, J.L., Blanco Morgado, Y., Spitaleri, D., van Pesch, V., Horakova, D., Ampapa, R., Patti, F., Macdonell, R., Al-Asmi, A., Gerlach, O., Oh, J., Tundia, N., Wong, S.L., Butzkueven, H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Subjects
relapse, Multiple Sclerosis, real-world data, Fingolimod Hydrochloride, switching, Dimethyl Fumarate, Neurosciences and neurology, MS, registry, Multiple Sclerosis, Relapsing-Remitting, Disability, Discontinuation, Real-world data, Registry, Relapse, Switching, Neurology, disability, Recurrence, Medicine and Health Sciences, Humans, Cladribine, Neurology (clinical), Registries, Immunosuppressive Agents, Retrospective Studies, Tablets, discontinuation
Abstract

Background: effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. Objectives: use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. Methods: retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). Results: cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. Conclusion: cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators., Financial support for this study was provided entirely by a contract with EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA (CrossRef Funder ID: 10.13039/100004755). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. The following authors are employed by the sponsor: NT and SLW.

Published
2023

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