Year: 2022
Type: dissertation
Study design: Observational Study
Abstract: Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Although great advances in MS treatment have been made, it remains one of the most common causes of neurological disability in young adults globally. The disease course can be highly variable. The emergence of effective disease modifying therapies (DMTs) for relapsing-remitting MS (RRMS) has created a need for blood and imaging biomarkers for disease activity and prognosis for improved treatment decisions. Aims of the study: To study which brain volume measures correlate with disability and cognition in a clinical cohort of relapsing and secondary progressive Finnish MS patients, and to evaluate whether a single-time-point brain volume measure could predict disability progression. A further aim was to study whether serum neurofilament light chain (sNfL) levels are affected by supplementation of vitamin D and correlate with magnetic resonance imaging (MRI) activity in interferon-beta-1b (IFN)-treated MS patients. Another aim was to compare outcomes of initial treatment with high-efficacy therapies vs starting therapy with mediumefficacy therapy in a propensity-matched cohort of Finnish RRMS patients. Results: Worse performance in Symbol Digit Modalities Test (SDMT) for cognition and higher Expanded Disability Status Scale (EDSS) for physical disability significantly correlated with smaller deep grey matter and total brain volumes. Even very early brain atrophy, such that atrophy was detected in thalamus only, was a negative prognostic marker for disability. Patients with only thalamic atrophy were at a higher risk for not reaching 2-year No Evidence of Disease Activity (NEDA) and for EDSS increase at 2 and 5 years than patients with no brain atrophy. In a small cohort of clinically stable IFN-treated patients, sNfL levels were similarly low in patients supplemented with high-dose vitamin D or placebo. Subclinical disease activity in MRI was associated with higher sNfL levels. Initiating MStherapy with high-efficacy DMTs significantly reduced the risk of 5-year disability progression and relapse compared to using moderate-efficacy DMT as first treatment. Conclusions: Measuring brain volume early in the disease course could aid therapeutic decision making. In clinically stable patients, elevated sNfL levels may assist detection of subclinical inflammatory disease activity. Early high-efficacy therapy in RRMS patients leads to better prognosis than initiating treatment with moderate-efficacy therapies.
Source: UTUPub (University of Turku)
Author: Kuutti, Katariina
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6981346837