A Longitudinal Study of Disability, Cognition and Gray Matter Atrophy in Early Multiple Sclerosis Patients According to Evidence of Disease Activity

Abstract

New treatment options may make “no evidence of disease activity” (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to “evidence of disease activity” (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8–2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0–1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity.

Symptoms of fatigue and depression is reflected in altered default mode network connectivity in multiple sclerosis

“…We included in total 74 MS patients at Oslo University Hospital for a prospective longitudinal study. Some other data from this study have been published earlier (15, 16). All participants were diagnosed between January 2009 and October 2012 with relapsing-remitting MS (RRMS) according to the revised McDonald Criteria (17) and were referred to brain MRI between January 2012 and January 2013.…”

“…The mean BDI sum score in our dataset was 9.1, which is lower than reported in some studies (5), but comparable with a Swedish study (36). Possible reasons for the relatively low BDI sum score in our sample include the low age, newly diagnosed RRMS, short disease duration and few brain lesions in our MS patients (15).…”

“…However, the associations between symptoms of fatigue and depression with DMN connectivity identified by rs-fMRI in our study suggest different pathophysiology for the two most prominent components revealed by the multivariate decomposition analysis of symptoms of fatigue and depression. Previous studies assessing cortical morphometry in an overlapping patient sample reported regional associations between cortical surface areas and several clinical manifestations, where the most prominent structural association were smaller cortical surface area and volume significantly associated with depressive symptoms (15).…”

Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

“…Sixty-six patients newly diagnosed with relapsing-remitting (RR) MS according to the revised 2010 McDonald criteria [17] were prospectively enrolled in this study. The patients were diagnosed with MS between January 2009 and October 2012, and recruited from an on-going longitudinal study at our institution [29]. All patients underwent a detailed neurological examination at baseline within 14.4 ± 9.6 months (range 1-34) from diagnosis.…”

“…This study is based on perfusion data from our previous baseline study [28] and on clinical data from approximately one-year follow-up [29]. We aimed to investigate whether there are differences in normalized perfusion measures between clinical subgroups of newly diagnosed MS patients, defined according to disease severity and disease activity.…”