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.

Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino Avellino Italy

Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases Istanbul Turkey

Brain and Mind Centre The University of Sydney Camperdown NSW Australia

Centre hospitalier de l'Universite de Montreal Montreal QC Canada

CISSS de Chaudière Appalache Levis QC Canada

Cliniques Universitaires Saint Luc Brussels Belgium

CORe Department of Medicine The University of Melbourne Melbourne VIC Australia; Department of Neurology The Royal Melbourne Hospital Melbourne VIC Australia

CSSS Saint Jérôme Saint Jerome QC Canada

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Medicine and Surgery University of Parma Parma Italy

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Neurology Razi Hospital Manouba Tunisia

Department of Neuroscience Azienda Ospedaliera Universitaria Modena Italy

Department of Neuroscience Central Clinical School Monash University Melbourne VIC Australia

Division of Neurology Department of Medicine Amiri Hospital Sharq Kuwait

Dokuz Eylul University Konak Izmir Turkey

Faculty of Medicine 19 Mayis University Samsun Turkey

Farabi Hospital KTU Faculty of Medicine Trabzon Turkey

Flinders University Adelaide SA Australia

Haydarpasa Numune Training and Research Hospital Istanbul Turkey

Hospital de Galdakao Usansolo Galdakao Spain

Hospital Germans Trias i Pujol Barcelona Spain

Hospital Universitario Virgen Macarena Sevilla Spain

IRCCS Istituto delle Scienze Neurologiche di Bologna UOSI Riabilitazione Sclerosi Multipla Bologna Italy Dipartimento di Scienze Biomediche e Neuromotorie Università di Bologna Bologna Italy

IRCCS Mondino Foundation Pavia Italy

Isfahan University of Medical Sciences Isfahan Iran Islamic Republic of

Kommunehospitalet Arhus C Denmark

Nehme and Therese Tohme Multiple Sclerosis Center American University of Beirut Medical Center Beirut Lebanon

Nemocnice Jihlava Jihlava Czech Republic

Neuro Rive Sud Quebec QC Canada

Ospedali Riuniti di Salerno Salerno Italy

School of Medicine and Public Health The University of Newcastle Australia Newcastle NSW Australia

School of Medicine Koc University Istanbul Turkey

The University of Queensland Brisbane QLD Australia

Universidade Metropolitana de Santos Santos Brazil

UOC Neurologia Azienda Sanitaria Unica Regionale Marche AV3 Macerata Italy

Westmead Hospital Sydney NSW Australia

Zuyderland Ziekenhuis Sittard Netherlands

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