RT Journal Article
T1 Early clinical markers of aggressive multiple sclerosis.
A1 Malpas, Charles B
A1 Manouchehrinia, Ali
A1 Sharmin, Sifat
A1 Roos, Izanne
A1 Horakova, Dana
A1 Havrdova, Eva Kubala
A1 Trojano, Maria
A1 Izquierdo, Guillermo
A1 Eichau, Sara
A1 Bergamaschi, Roberto
A1 Sola, Patrizia
A1 Ferraro, Diana
A1 Lugaresi, Alessandra
A1 Prat, Alexandre
A1 Girard, Marc
A1 Duquette, Pierre
A1 Grammond, Pierre
A1 Grand'Maison, Francois
A1 Ozakbas, Serkan
A1 Van Pesch, Vincent
A1 Granella, Franco
A1 Hupperts, Raymond
A1 Pucci, Eugenio
A1 Boz, Cavit
A1 Sidhom, Youssef
A1 Gouider, Riadh
A1 Spitaleri, Daniele
A1 Soysal, Aysun
A1 Petersen, Thor
A1 Verheul, Freek
A1 Karabudak, Rana
A1 Turkoglu, Recai
A1 Ramo-Tello, Cristina
A1 Terzi, Murat
A1 Cristiano, Edgardo
A1 Slee, Mark
A1 McCombe, Pamela
A1 Macdonell, Richard
A1 Fragoso, Yara
A1 Olascoaga, Javier
A1 Altintas, Ayse
A1 Olsson, Tomas
A1 Butzkueven, Helmut
A1 Hillert, Jan
A1 Kalincik, Tomas
K1 aggressive disease
K1 disability
K1 multiple sclerosis
K1 precision medicine
K1 prediction
AB Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis.
YR 2020
FD 2020
LK http://hdl.handle.net/10668/15534
UL http://hdl.handle.net/10668/15534
LA en
DS RISalud
RD Apr 6, 2025