Thalamic Atrophy Without Whole Brain Atrophy Is Associated With Absence of 2-Year NEDA in Multiple Sclerosis.

Jyrki Lötjönen,Juha Rinne,Jari O Karhu,Juha Koikkalainen,Matias Viitala,Teemu Paavilainen,Merja Soilu-Hänninen,Katariina Hänninen

doi:10.3389/fneur.2019.00459

Abstract

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.

Highlights

The quantification of brain atrophy by MRI has become an increasingly important part of evaluating neurodegeneration in MS [1, 2]
There were no significant differences between the relapsing MS (RMS) and secondary progressive MS (SPMS) patients in their comorbidities, alcohol consumption, education status, smoking habits, serum vitamin D levels or BMI
There was no significant difference in the Expanded Disability Status Scale (EDSS), relapses or SDMT points between Groups 1 and 2 at baseline

Summary

Introduction

The quantification of brain atrophy by MRI has become an increasingly important part of evaluating neurodegeneration in MS [1, 2]. Atrophy measures can reflect the damage on the central nervous system (CNS) caused by the pathological processes of the disease. Brain atrophy occurs in all clinical stages of untreated MS patients at a rate of 0.5–1.35%/year, in comparison with 0.1–0.3%/year in healthy individuals [1]. Several studies have shown associations between GM atrophy and measures of disease progression, such as accumulation of physical disability [3, 4] and cognitive impairment [5]. Thalamic atrophy occurs from early on in the disease course [6] and it has been associated with the transition from clinically isolated syndrome (CIS) to definite MS [7]. Thalamic atrophy has been shown to correlate with accumulation of disability in patients with MS [8]

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