Projects per year
Abstract
Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
| Original language | English |
|---|---|
| Pages (from-to) | 755-766 |
| Number of pages | 12 |
| Journal | Multiple Sclerosis Journal |
| Volume | 27 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Apr 2021 |
Keywords
- Multiple sclerosis
- disability outcome
- early symptomatology
- prognostic marker
- cerebellar
- brainstem
Projects
-
Biomarkers to prevent disability in multiple sclerosis
Kalincik, T., Havrdova, E. K., Kuhle, J., Olsson, T., Hillert, J., Taylor, B. V. M., Malpas, C., Kilpatrick, T. J., Barnett, M. & Buzzard, K.
1/07/19 → 30/06/22
Project: Research
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Le, M., Malpas, C., Sharmin, S., Horáková, D., Havrdova, E., Trojano, M., Izquierdo, G., Eichau, S., Ozakbas, S., Lugaresi, A., Prat, A., Girard, M., Duquette, P., Larochelle, C., Alroughani, R., Bergamaschi, R., Sola, P., Ferraro, D., Grammond, P., ... on behalf of the MSBase Study Group (2021). Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis. Multiple Sclerosis Journal, 27(5), 755-766. https://doi.org/10.1177/1352458520926955
Le, Minh ; Malpas, Charles ; Sharmin, Sifat ; Horáková, Dana ; Havrdova, Eva ; Trojano, Maria ; Izquierdo, Guillermo ; Eichau, Sara ; Ozakbas, Serkan ; Lugaresi, Alessandra ; Prat, Alexandre ; Girard, Marc ; Duquette, Pierre ; Larochelle, Catherine ; Alroughani, Raed ; Bergamaschi, Roberto ; Sola, Patrizia ; Ferraro, Diana ; Grammond, Pierre ; Grand’ Maison, Francois ; Terzi, Murat ; Boz, Cavit ; Hupperts, Raymond ; Butzkueven, Helmut ; Pucci, Eugenio ; Granella, Franco ; Van Pesch, Vincent ; Soysal, Aysun ; Yamout, Bassem I. ; Lechner-Scott, Jeannette ; Spitaleri, Daniele L.A. ; Ampapa, Radek ; Turkoglu, Recai ; Iuliano, Gerardo ; Ramo-Tello, Cristina ; Sanchez-Menoyo, Jose Luis ; Sidhom, Youssef ; Gouider, Riadh ; Shaygannejad, Vahid ; Prevost, Julie ; Altintas, Ayse ; Fragoso, Yara Dadalti ; McCombe, Pamela Ann ; Petersen, Thor ; Slee, Mark ; Barnett, Michael H. ; Vucic, Steve ; Van Der Walt, Anneke ; Kalincik, Tomas ; on behalf of the MSBase Study Group. / Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis. In: Multiple Sclerosis Journal. 2021 ; Vol. 27, No. 5. pp. 755-766.
@article{59cbc6c5b50048c2858f0ab7d4ec5c44,
title = "Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis",
abstract = "Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.",
keywords = "Multiple sclerosis, disability outcome, early symptomatology, prognostic marker, cerebellar, brainstem",
author = "Minh Le and Charles Malpas and Sifat Sharmin and Dana Hor{\'a}kov{\'a} and Eva Havrdova and Maria Trojano and Guillermo Izquierdo and Sara Eichau and Serkan Ozakbas and Alessandra Lugaresi and Alexandre Prat and Marc Girard and Pierre Duquette and Catherine Larochelle and Raed Alroughani and Roberto Bergamaschi and Patrizia Sola and Diana Ferraro and Pierre Grammond and {Grand{\textquoteright} Maison}, Francois and Murat Terzi and Cavit Boz and Raymond Hupperts and Helmut Butzkueven and Eugenio Pucci and Franco Granella and {Van Pesch}, Vincent and Aysun Soysal and Yamout, {Bassem I.} and Jeannette Lechner-Scott and Spitaleri, {Daniele L.A.} and Radek Ampapa and Recai Turkoglu and Gerardo Iuliano and Cristina Ramo-Tello and Sanchez-Menoyo, {Jose Luis} and Youssef Sidhom and Riadh Gouider and Vahid Shaygannejad and Julie Prevost and Ayse Altintas and Fragoso, {Yara Dadalti} and McCombe, {Pamela Ann} and Thor Petersen and Mark Slee and Barnett, {Michael H.} and Steve Vucic and {Van Der Walt}, Anneke and Tomas Kalincik and {on behalf of the MSBase Study Group}",
note = "Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.V.H.L., C.B.M. and S.S. report no disclosure. D.H. received speaker honoraria and consulting fees from Biogen, Merck, Roche, Teva and Novartis, as well as support for research activities from Biogen and research grant from Czech Ministry of Education PROGRES Q27/LF1. E.K.H. received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva and support for research activities from Czech Ministry of Education (project Progres Q27/LF1). M.T. received speaker honoraria from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck, Teva, Novartis and Almirall; has received research grants for her institution from Biogen Idec, Merck and Novartis. G.I. received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva. S.E. received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. S.O. reports no disclosure. A.L. has served as a Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme and Teva Advisory Board Member. She received travel grants and honoraria from Mylan, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Novartis. A.P. reports no disclosure. M.G. received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research (CIHR). P.D. served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme and Teva Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis and Genzyme. C.L. received consulting and speaker fees from Celgene, Actelion, EMD-Serono, Teva Canada Innovation, Roche, Biogen, Novartis and Genzyme Sanofi. She holds grants from the CIHR, the MS Society of Canada and the Grant for Multiple Sclerosis Innovation (GMSI) from Merck-EMD-Serono. She is a junior research scholar of the Fonds de recherche du Qu{\'e}bec-Sant{\'e} (FRQS). R.A. received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi Genzyme. R.B. received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi Aventis and Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis and Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi Aventis and Teva. P.S. served on scientific advisory boards for Biogen Idec and Teva; she has received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her institution from Bayer, Biogen, Merck, Novartis, Sanofi and Teva. D.F. received travel grants and/or speaker honoraria from Merck, Teva, Novartis, Biogen and Sanofi Genzyme. P.G. is a Merck, Novartis, Teva Neuroscience, Biogen and Genzyme advisory board member, consultant for Merck, received payments for lectures by Merck, Teva Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva Neuroscience and Novartis. F.G'M. received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals. M.T. received travel grants from Novartis, Bayer Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. C.B. received conference travel support from Biogen, Novartis, Bayer Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. R.H. received honoraria as consultant on scientific advisory boards from Merck, Biogen, Genzyme-Sanofi and Teva, research funding from Merck and Biogen, and speaker honoraria from Sanofi Genzyme and Novartis. H.B. served on scientific advisory boards for Biogen, Novartis and Sanofi Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis and has received research support from Merck, Novartis and Biogen. E.P. reports the following relationships that were present during the 36 months prior to writing this paper: he has received honoraria and/or travel grants from Roche, Sanofi Genzyme, Novartis, Biogen, Merck and Teva; he has received equipment from {\textquoteleft}Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche{\textquoteright}. F.G. received research grant from Biogen, served on scientific advisory boards for Biogen, Novartis, Merck and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen, Merck, Sanofi Aventis and Almirall. V.V.P. received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma and Bayer Schering. A.S. and B.Y. report no disclosure. J.L-S. accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Biogen, Sanofi Genzyme, Merck, Novartis and Teva and has been involved in clinical trials with Biogen, Clene, Novartis and Teva. D.S. received honoraria as a consultant on scientific advisory boards by Bayer Schering, Novartis and Sanofi Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck. R.A. received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in clinical trials by Biogen, Novartis, Teva and Actelion. R.T. reports no disclosure. G.I. had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis and Teva. C.R-T. received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Merck, Genzyme and Almirall. J.L.S-M. accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen. Y.S., R.G. and V.S. report no disclosure. J.P. accepted travel compensation from Novartis, Biogen, Genzyme and Teva and speaking honoraria from Biogen, Novartis, Genzyme and Teva. A.A. received personal fees and speaker honoraria from Teva, Merck, Biogen–Gen Pharma, Roche, Novartis, Bayer, Sanofi Genzyme; received travel and registration grants from Merck, Biogen–Gen Pharma, Roche, Sanofi Genzyme and Bayer. Y.F. received honoraria as a consultant on scientific advisory boards by Novartis, Teva, Roche and Sanofi Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva, Roche and Merck. P.A.McC. received funding or speaker honoraria from Biogen, Merck, Novartis and Sanofi Aventis. T.P. received funding or speaker honoraria from Biogen, Merck, Novartis, Bayer Schering, Sanofi Aventis, Roche and Genzyme. M.S. has participated in, but not received honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi Aventis and Novartis. M.B. served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. S.V. reports no disclosure. A.van Der W. served on scientific advisory boards for Biogen, Novartis, Merck and Genzyme. She has received conference travel support from Novartis, Merck, Biogen, Genzyme and Roche. She has received research support from Merck, Novartis and Biogen. T.K. served on scientific advisory boards for Roche, Genzyme Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme Sanofi, Teva, BioCSL and Merck and received research support from Biogen. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was financially supported by the National Health and Medical Research Council (1140766, 1129189, 1157717). Publisher Copyright: {\textcopyright} The Author(s), 2020.",
year = "2021",
month = apr,
doi = "10.1177/1352458520926955",
language = "English",
volume = "27",
pages = "755--766",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "5",
}
Le, M, Malpas, C, Sharmin, S, Horáková, D, Havrdova, E, Trojano, M, Izquierdo, G, Eichau, S, Ozakbas, S, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Larochelle, C, Alroughani, R, Bergamaschi, R, Sola, P, Ferraro, D, Grammond, P, Grand’ Maison, F, Terzi, M, Boz, C, Hupperts, R, Butzkueven, H, Pucci, E, Granella, F, Van Pesch, V, Soysal, A, Yamout, BI, Lechner-Scott, J, Spitaleri, DLA, Ampapa, R, Turkoglu, R, Iuliano, G, Ramo-Tello, C, Sanchez-Menoyo, JL, Sidhom, Y, Gouider, R, Shaygannejad, V, Prevost, J, Altintas, A, Fragoso, YD, McCombe, PA, Petersen, T, Slee, M, Barnett, MH, Vucic, S, Van Der Walt, A, Kalincik, T & on behalf of the MSBase Study Group 2021, 'Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis', Multiple Sclerosis Journal, vol. 27, no. 5, pp. 755-766. https://doi.org/10.1177/1352458520926955
Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis. / Le, Minh; Malpas, Charles; Sharmin, Sifat; Horáková, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Eichau, Sara; Ozakbas, Serkan; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Larochelle, Catherine; Alroughani, Raed; Bergamaschi, Roberto; Sola, Patrizia; Ferraro, Diana; Grammond, Pierre; Grand’ Maison, Francois; Terzi, Murat; Boz, Cavit; Hupperts, Raymond; Butzkueven, Helmut; Pucci, Eugenio; Granella, Franco; Van Pesch, Vincent; Soysal, Aysun; Yamout, Bassem I.; Lechner-Scott, Jeannette; Spitaleri, Daniele L.A.; Ampapa, Radek; Turkoglu, Recai; Iuliano, Gerardo; Ramo-Tello, Cristina; Sanchez-Menoyo, Jose Luis; Sidhom, Youssef; Gouider, Riadh; Shaygannejad, Vahid; Prevost, Julie; Altintas, Ayse; Fragoso, Yara Dadalti; McCombe, Pamela Ann; Petersen, Thor; Slee, Mark; Barnett, Michael H.; Vucic, Steve; Van Der Walt, Anneke; Kalincik, Tomas; on behalf of the MSBase Study Group.
In: Multiple Sclerosis Journal, Vol. 27, No. 5, 04.2021, p. 755-766.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis
AU - Le, Minh
AU - Malpas, Charles
AU - Sharmin, Sifat
AU - Horáková, Dana
AU - Havrdova, Eva
AU - Trojano, Maria
AU - Izquierdo, Guillermo
AU - Eichau, Sara
AU - Ozakbas, Serkan
AU - Lugaresi, Alessandra
AU - Prat, Alexandre
AU - Girard, Marc
AU - Duquette, Pierre
AU - Larochelle, Catherine
AU - Alroughani, Raed
AU - Bergamaschi, Roberto
AU - Sola, Patrizia
AU - Ferraro, Diana
AU - Grammond, Pierre
AU - Grand’ Maison, Francois
AU - Terzi, Murat
AU - Boz, Cavit
AU - Hupperts, Raymond
AU - Butzkueven, Helmut
AU - Pucci, Eugenio
AU - Granella, Franco
AU - Van Pesch, Vincent
AU - Soysal, Aysun
AU - Yamout, Bassem I.
AU - Lechner-Scott, Jeannette
AU - Spitaleri, Daniele L.A.
AU - Ampapa, Radek
AU - Turkoglu, Recai
AU - Iuliano, Gerardo
AU - Ramo-Tello, Cristina
AU - Sanchez-Menoyo, Jose Luis
AU - Sidhom, Youssef
AU - Gouider, Riadh
AU - Shaygannejad, Vahid
AU - Prevost, Julie
AU - Altintas, Ayse
AU - Fragoso, Yara Dadalti
AU - McCombe, Pamela Ann
AU - Petersen, Thor
AU - Slee, Mark
AU - Barnett, Michael H.
AU - Vucic, Steve
AU - Van Der Walt, Anneke
AU - Kalincik, Tomas
AU - on behalf of the MSBase Study Group
N1 - Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.V.H.L., C.B.M. and S.S. report no disclosure. D.H. received speaker honoraria and consulting fees from Biogen, Merck, Roche, Teva and Novartis, as well as support for research activities from Biogen and research grant from Czech Ministry of Education PROGRES Q27/LF1. E.K.H. received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva and support for research activities from Czech Ministry of Education (project Progres Q27/LF1). M.T. received speaker honoraria from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck, Teva, Novartis and Almirall; has received research grants for her institution from Biogen Idec, Merck and Novartis. G.I. received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva. S.E. received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. S.O. reports no disclosure. A.L. has served as a Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme and Teva Advisory Board Member. She received travel grants and honoraria from Mylan, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Novartis. A.P. reports no disclosure. M.G. received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research (CIHR). P.D. served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme and Teva Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis and Genzyme. C.L. received consulting and speaker fees from Celgene, Actelion, EMD-Serono, Teva Canada Innovation, Roche, Biogen, Novartis and Genzyme Sanofi. She holds grants from the CIHR, the MS Society of Canada and the Grant for Multiple Sclerosis Innovation (GMSI) from Merck-EMD-Serono. She is a junior research scholar of the Fonds de recherche du Québec-Santé (FRQS). R.A. received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi Genzyme. R.B. received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi Aventis and Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis and Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi Aventis and Teva. P.S. served on scientific advisory boards for Biogen Idec and Teva; she has received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her institution from Bayer, Biogen, Merck, Novartis, Sanofi and Teva. D.F. received travel grants and/or speaker honoraria from Merck, Teva, Novartis, Biogen and Sanofi Genzyme. P.G. is a Merck, Novartis, Teva Neuroscience, Biogen and Genzyme advisory board member, consultant for Merck, received payments for lectures by Merck, Teva Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva Neuroscience and Novartis. F.G'M. received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals. M.T. received travel grants from Novartis, Bayer Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. C.B. received conference travel support from Biogen, Novartis, Bayer Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. R.H. received honoraria as consultant on scientific advisory boards from Merck, Biogen, Genzyme-Sanofi and Teva, research funding from Merck and Biogen, and speaker honoraria from Sanofi Genzyme and Novartis. H.B. served on scientific advisory boards for Biogen, Novartis and Sanofi Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis and has received research support from Merck, Novartis and Biogen. E.P. reports the following relationships that were present during the 36 months prior to writing this paper: he has received honoraria and/or travel grants from Roche, Sanofi Genzyme, Novartis, Biogen, Merck and Teva; he has received equipment from ‘Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche’. F.G. received research grant from Biogen, served on scientific advisory boards for Biogen, Novartis, Merck and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen, Merck, Sanofi Aventis and Almirall. V.V.P. received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma and Bayer Schering. A.S. and B.Y. report no disclosure. J.L-S. accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Biogen, Sanofi Genzyme, Merck, Novartis and Teva and has been involved in clinical trials with Biogen, Clene, Novartis and Teva. D.S. received honoraria as a consultant on scientific advisory boards by Bayer Schering, Novartis and Sanofi Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck. R.A. received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in clinical trials by Biogen, Novartis, Teva and Actelion. R.T. reports no disclosure. G.I. had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis and Teva. C.R-T. received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Merck, Genzyme and Almirall. J.L.S-M. accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen. Y.S., R.G. and V.S. report no disclosure. J.P. accepted travel compensation from Novartis, Biogen, Genzyme and Teva and speaking honoraria from Biogen, Novartis, Genzyme and Teva. A.A. received personal fees and speaker honoraria from Teva, Merck, Biogen–Gen Pharma, Roche, Novartis, Bayer, Sanofi Genzyme; received travel and registration grants from Merck, Biogen–Gen Pharma, Roche, Sanofi Genzyme and Bayer. Y.F. received honoraria as a consultant on scientific advisory boards by Novartis, Teva, Roche and Sanofi Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva, Roche and Merck. P.A.McC. received funding or speaker honoraria from Biogen, Merck, Novartis and Sanofi Aventis. T.P. received funding or speaker honoraria from Biogen, Merck, Novartis, Bayer Schering, Sanofi Aventis, Roche and Genzyme. M.S. has participated in, but not received honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi Aventis and Novartis. M.B. served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis. S.V. reports no disclosure. A.van Der W. served on scientific advisory boards for Biogen, Novartis, Merck and Genzyme. She has received conference travel support from Novartis, Merck, Biogen, Genzyme and Roche. She has received research support from Merck, Novartis and Biogen. T.K. served on scientific advisory boards for Roche, Genzyme Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme Sanofi, Teva, BioCSL and Merck and received research support from Biogen. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was financially supported by the National Health and Medical Research Council (1140766, 1129189, 1157717). Publisher Copyright: © The Author(s), 2020.
PY - 2021/4
Y1 - 2021/4
N2 - Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
AB - Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods: This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores. Results: The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk. Conclusion: Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
KW - Multiple sclerosis
KW - disability outcome
KW - early symptomatology
KW - prognostic marker
KW - cerebellar
KW - brainstem
UR - http://www.scopus.com/inward/record.url?scp=85102729504&partnerID=8YFLogxK
U2 - 10.1177/1352458520926955
DO - 10.1177/1352458520926955
M3 - Article
C2 - 32538713
AN - SCOPUS:85102729504
VL - 27
SP - 755
EP - 766
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
SN - 1352-4585
IS - 5
ER -
Le M, Malpas C, Sharmin S, Horáková D, Havrdova E, Trojano M et al. Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis. Multiple Sclerosis Journal. 2021 Apr;27(5):755-766. https://doi.org/10.1177/1352458520926955