Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis

Minh Le; Charles Malpas; Sifat Sharmin; Dana Horakova; Eva Havrdova; Maria Trojano; Guillermo Izquierdo; Sara Eichau; Serkan Ozakbas; Alessandra Lugaresi; Alexandre Prat; Marc Girard; Pierre Pascal Duquette; Catherine Larochelle; Raed A Alroughani; Roberto Bergamaschi; Patrizia Sola; DIana Ferraro; Pierre Grammond; Francois Grand’Maison; Murat Terzi; Cavit Boz; Raymond Hupperts; Helmut Butzkueven; Eugenio Pucci; Franco Granella; Vincent Van Pesch; Aysun Soysal; Bassem I. Yamout; Jeannette Lechner-Scott; Daniele La Spitaleri; Radek Ampapa; Recai Turkoglu; Gerardo Iuliano; Cristina Ramo-Tello; Jose Luis Sanchez-Menoyo; Youssef Sidhom; Riadh Gouider; Vahid Shaygannejad; Julie Prevost; Ayse Altintas; Yara Dadalti Fragoso; Pamela Ann McCombe; Thor Petersen; Mark Slee; Michael H Barnett; Steve Vucic; Anneke Van Der Walt; Tomas Kalincik; on behalf of the MSBase Study Group

doi:10.1177/1352458520926955

Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis

Minh Le, Charles Malpas, Sifat Sharmin, Dana Horakova, Eva Havrdova, Maria Trojano, Guillermo Izquierdo, Sara Eichau, Serkan Ozakbas, Alessandra Lugaresi, Alexandre Prat, Marc Girard, Pierre Pascal Duquette, Catherine Larochelle, Raed A Alroughani, Roberto Bergamaschi, Patrizia Sola, DIana Ferraro, Pierre Grammond, Francois Grand’MaisonMurat Terzi, Cavit Boz, Raymond Hupperts, Helmut Butzkueven, Eugenio Pucci, Franco Granella, Vincent Van Pesch, Aysun Soysal, Bassem I. Yamout, Jeannette Lechner-Scott, Daniele La Spitaleri, Radek Ampapa, Recai Turkoglu, Gerardo Iuliano, Cristina Ramo-Tello, Jose Luis Sanchez-Menoyo, Youssef Sidhom, Riadh Gouider, Vahid Shaygannejad, Julie Prevost, Ayse Altintas, Yara Dadalti Fragoso, Pamela Ann McCombe, Thor Petersen, Mark Slee, Michael H Barnett, Steve Vucic, Anneke Van Der Walt, Tomas Kalincik, on behalf of the MSBase Study Group

Department of Neuroscience

Research output: Contribution to journal › Article › Research › peer-review

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 (beta = 0.16,p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89,p = 0.01) and EDSS (beta = -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
Number of pages	12
Journal	Multiple Sclerosis Journal
DOIs	https://doi.org/10.1177/1352458520926955
Publication status	Accepted/In press - Jun 2020

Keywords

Multiple sclerosis
disability outcome
early symptomatology
prognostic marker
cerebellar
brainstem

Access to Document

10.1177/1352458520926955

Cite this

Le, M., Malpas, C., Sharmin, S., Horakova, D., Havrdova, E., Trojano, M., Izquierdo, G., Eichau, S., Ozakbas, S., Lugaresi, A., Prat, A., Girard, M., Duquette, P. P., Larochelle, C., Alroughani, R. A., Bergamaschi, R., Sola, P., Ferraro, DI., Grammond, P., ... on behalf of the MSBase Study Group (Accepted/In press). Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis. Multiple Sclerosis Journal. https://doi.org/10.1177/1352458520926955

Le, Minh ; Malpas, Charles ; Sharmin, Sifat ; Horakova, Dana ; Havrdova, Eva ; Trojano, Maria ; Izquierdo, Guillermo ; Eichau, Sara ; Ozakbas, Serkan ; Lugaresi, Alessandra ; Prat, Alexandre ; Girard, Marc ; Duquette, Pierre Pascal ; Larochelle, Catherine ; Alroughani, Raed A ; 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 ; La Spitaleri, Daniele ; 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. 2020.

@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 (beta = 0.16,p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89,p = 0.01) and EDSS (beta = -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 Horakova 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 Duquette, {Pierre Pascal} and Catherine Larochelle and Alroughani, {Raed A} and Roberto Bergamaschi and Patrizia Sola and DIana Ferraro and Pierre Grammond and Francois Grand{\textquoteright}Maison 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 {La Spitaleri}, Daniele 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 = "Manuscript ID: MSJ 19-0755.R2",

year = "2020",

month = jun,

doi = "10.1177/1352458520926955",

language = "English",

journal = "Multiple Sclerosis Journal",

issn = "1352-4585",

publisher = "SAGE Publications Ltd",

}

Le, M, Malpas, C, Sharmin, S, Horakova, D, Havrdova, E, Trojano, M, Izquierdo, G, Eichau, S, Ozakbas, S, Lugaresi, A, Prat, A, Girard, M, Duquette, PP, Larochelle, C, Alroughani, RA, Bergamaschi, R, Sola, P, Ferraro, DI, 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, La Spitaleri, D, 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 2020, 'Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis', Multiple Sclerosis Journal. https://doi.org/10.1177/1352458520926955

Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis. / Le, Minh; Malpas, Charles; Sharmin, Sifat; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Eichau, Sara; Ozakbas, Serkan; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre Pascal; Larochelle, Catherine; Alroughani, Raed A; 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; La Spitaleri, Daniele; 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, 06.2020.

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 - Horakova, 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 Pascal

AU - Larochelle, Catherine

AU - Alroughani, Raed A

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 - La Spitaleri, Daniele

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 - Manuscript ID: MSJ 19-0755.R2

PY - 2020/6

Y1 - 2020/6

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 (beta = 0.16,p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89,p = 0.01) and EDSS (beta = -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 (beta = 0.16,p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89,p = 0.01) and EDSS (beta = -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

U2 - 10.1177/1352458520926955

DO - 10.1177/1352458520926955

M3 - Article

C2 - 32538713

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

ER -