Development of Cortical Lesion Volumes on Double Inversion Recovery MRI in Patients With Relapse-Onset Multiple Sclerosis

Abstract

Background and Objective: In multiple sclerosis (MS) patients, Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to detect cortical lesions (CL). While the quantity and distribution of CLs seems to be associated with patients' disease course, literature lacks frequent assessments of CL volumes (CL-V) in this context. We investigated the reliability of DIR for the longitudinal assessment of CL-V development with frequent follow-up MRIs and examined the course of CL-V progressions in relation to white-matter lesions (WML), contrast enhancing lesions (CEL) and clinical parameters in patients with Relapsing-Remitting Multiple Sclerosis (RRMS). Methods: In this post-hoc analysis, image- and clinical data of a subset of 24 subjects that were part of a phase IIa clinical trial on the "Safety, Tolerability and Mechanisms of Action of Boswellic Acids in Multiple Sclerosis (SABA)" (ClinicalTrials.gov, NCT01450124) were included. The study was divided in three phases (screening, treatment, study-end). All patients received 12 MRI follow-up-examinations (including DIR) during a 16-months period. CL-Vs were assessed for each patient on each follow-up MRI separately by two experienced neuroradiologists. Results of neurological screening tests, as well as other MRI parameters (WML number and volume and CELs) were included from the SABA investigation data. Results: Inter-rater agreement regarding CL-V assessment over time was good-to-excellent (κ = 0.89). Mean intraobserver variability was 1.1%. In all patients, a total number of 218 CLs was found. Total CL-Vs of all patients increased during the 4 months of baseline screening followed by a continuous and significant decrease from month 5 until study-end (p < 0.001, Kendall'W = 0.413). A positive association between WML volumes and CL-Vs was observed during baseline screening. Decreased CL-V were associated with lower EDSS and also with improvements of SDMT- and SCRIPPS scores. Conclusion: DIR MRI seems to be a reliable tool for the frequent assessment of CL-Vs. Overall CL-Vs decreased during the follow-up period and were associated with improvements of cognitive and disability status scores. Our results suggest the presence of short-term CL-V dynamics in RRMS patients and we presume that the laborious evaluation of lesion volumes may be worthwhile for future investigations. Clinical Trial Numbers: www.ClinicalTrials.gov, "The SABA trial"; number: NCT01450124.

Keywords: cerebral cortex; cortical lesion volume; double inversion recovery; inflammation; magnetic resonance imaging; multiple sclerosis.

Figures

Figure 1

Examples of cortical lesion volume changes during follow-up. This figure displays cortical lesion volume (CL-V) changes of several lesions followed over the time course in different MS patients. Distinct volume reduction of a CL in the frontal cortex (A) marked with a white arrow at month 2 of screening phase (SP, left side) and month 3 of treatment phase (TP, right side). Rather marginal, but still notable CL-V reductions found in the cortices of patients in (B) (1st month of SP left and 2nd month of TP right) and (C) (2nd month of SP left and SE right). White arrow in (D) (4th month of SP left and 1st month of TP right) points at a cortical lesion with a measurable volume decrease. Dotted white arrow is indicating a CL with no measurable volume change.

Figure 2

Cortical lesion volume progression during follow-up. This figure displays the progression of the cortical lesion volume (CL-V) during the time course. From month 1–5, CL-V is fluctuating with a tendency to an increase of volume. From month 5 onwards, a continuous decrease of CL-V was detected. n = 24. The circles represent the median values with the corresponding 25th percentile and 75th percentile.

Figure 3

Development of the course of cortical-, white-matter- and contrast enhancing lesions. Boxplots in this figure display the development of lesion numbers and the number of new lesions during the 16-month observation period (n = 24). CL, cortical lesion; WML, white matter lesion; CEL, contrast enhancing lesion.