Purpose: To study which brain volume measures best differentiate early relapsing MS (RMS) and secondary progressive MS (SPMS) patients and correlate with disability and cognition. To test whether isolated thalamic atrophy at study baseline correlates with NEDA (no evidence of disease activity) at 2 years. Methods: Total and regional brain volumes were measured from 24 newly diagnosed RMS patients 6 months after initiation of therapy and 2 years thereafter, and in 36 SPMS patients. Volumes were measured by SIENAX and cNeuro. The patients were divided into subgroups based on whole brain parenchyma (BP) and thalamic atrophy at baseline. Standard scores ( z -scores) were computed by comparing individual brain volumes against healthy controls. A z -score cut-off of −1.96 was applied to separate atrophic from normal brain volumes. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed at baseline and at 2 years. Differences in achieving NEDA-3, NEDA-4, EDSS progression, and SDMT change were analyzed between patients with no thalamic or BP atrophy and in patients with isolated thalamic atrophy at baseline. Results: At baseline, 7 SPMS and 12 RMS patients had no brain atrophy, 8 SPMS and 10 RMS patients had isolated thalamic atrophy and 2 RMS and 20 SPMS patients had both BP and thalamic atrophy. NEDA-3 was reached in 11/19 patients with no brain atrophy but only in 2/16 patients with isolated thalamic atrophy ( p = 0.012). NEDA-4 was reached in 7/19 patients with no brain atrophy and in 1/16 of the patients with isolated thalamic atrophy ( p = 0.047). At 2 years, EDSS was same or better in 16/19 patients with no brain atrophy but only in 5/17 patients with isolated thalamic atrophy ( p = 0.002). There was no significant difference in the EDSS, relapses or SDMT between patients with isolated thalamic atrophy and no atrophy at baseline. Conclusion: Patients with isolated thalamic atrophy were at a higher risk for not reaching 2-year NEDA-3 and for EDSS increase than patients with no identified brain atrophy. The groups were clinically indistinguishable. A single measurement of thalamic and whole brain atrophy could help identify patients needing most effective therapies from early on.
Given the high risk for stroke in this MS population and the observed complexity among the coincident common risk factors for circulatory diseases, the high risk for type 1 diabetes and common infections raise a need to recognize patients at risk with these conditions and with the other known risk factors such as metabolic syndrome and smoking. The survival disadvantage related to circulatory diseases observed in general population is true also in MS and should be recognized to reduce the burden of disease and premature mortality in MS.
Purpose: Thalamus is among the first brain regions to become atrophic in multiple sclerosis (MS). We studied whether thalamic atrophy predicts disability progression at 5 years in a cohort of Finnish MS patients. Methods: Global and regional brain volumes were measured from 24 newly diagnosed relapsing MS (RMS) patients 6 months after initiation of therapy and from 36 secondary progressive MS (SPMS) patients. The patients were divided into groups based on baseline whole brain parenchymal (BP) and thalamic atrophy. Standard scores (z scores) were computed by comparing individual brain volumes with healthy controls. A z score cutoff of −1.96 was applied to separate atrophic from normal brain volumes. The Expanded Disability Status Scale (EDSS), brain magnetic resonance imaging (MRI) findings, and relapses were assessed at baseline and at 2 years and EDSS progression at 5 years. Results: Baseline thalamus volume predicted disability in 5 years in a logistic regression model (p = 0.031). At 5 years, EDSS was same or better in 12 of 18 patients with no brain atrophy at baseline but only in 5 of 18 patients with isolated thalamic atrophy [odds ratio (OR) (95% CI) = 5.2 (1.25, 21.57)]. The patients with isolated thalamic atrophy had more escalations of disease-modifying therapies during follow-up. Conclusion: Patients with thalamic atrophy at baseline were at a higher risk for 5-year EDSS increase than patients with no identified brain atrophy. Brain volume measurement at a single time point could help predict disability progression in MS and complement clinical and routine MRI evaluation in therapeutic decision-making.
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