Background

Steroid treatment is a first-line therapy in acute multiple sclerosis (MS) episodes. While it is well-established that there is an inverse relationship between serum steroid-levels and decreases of cortical thickness (CT), little is known about the effects of steroid treatment during MS relapses on CT.

Objectives

In this study, we investigated whether CT changes occur in MS patients following steroid treatment after the first clinical episode in MS in a retrospective design. Additionally, we aimed to assess whether such effects were sustained.

Methods

T1-weighted magnetic resonance (MR) images were acquired from 8 MS patients during their first clinical episode (7 females, median age 27 years). At the time of that baseline scan, all patients were within 5 days of onset of prednisolone treatment (1000mg/day i.v.; steroid treatment was stopped after these 5 days). A first follow-up scan was acquired 4 weeks later. To check for sustained effects on CT (post-hoc), a second follow-up scan, 8 weeks after baseline, was acquired. Additionally, data from 8 age- and sex-matched healthy controls (HC) was acquired (baseline and 4 weeks later).

CT maps from all subjects were generated individually and parceled into 68 regions using the Desikan-Killiany atlas. We used a repeated measures analysis of variance to test for significant differences of CT changes between MS and HC over time. Family-wise error-corrected p-values (p_FWER) were calculated using a Monte-Carlo permutation procedure. Since the ANOVA yielded a significant interaction for one region, we investigated post-hoc whether that effect was still observable another four weeks after the first follow-up. To test for this effect, we used a paired t-test to compare mean CT levels of that region within the patient group between 4 and 8 weeks after treatment, as well as baseline vs. 8 weeks after treatment.

Results

The ANOVA showed a significant interaction of group x time for the medial orbitofrontal cortex (mOFC) of the right hemisphere (F = 21.956 , p_FWER = 0.011), with MS patients showing a decrease of mean CT within that region over time. No main effects were observed. A post-hoc paired t-test comparing the CT means within the mOFC at a second follow-up scans eight weeks after baseline revealed no significant difference between follow-up 1 and follow-up 2 (t₇ = -0.9841, p = 0.3578) and approached significance for the comparison between baseline and follow-up 2 (t₇ = 2.3513, p = 0.0510).

Conclusions

Our results provide first evidence that steroid treatment during the first acute episode in MS was associated with cortical thinning in the mOFC, which tended to reverse after eight weeks of steroid-free treatment. Although these results need to be further validated in a larger cohort, our results suggest that steroid treatment potentially associates to atrophy in the medial orbitofrontal cortex; an effect which – if validated – should be taken into account for MS therapy.

Background

Steroid treatment is a first-line therapy in acute multiple sclerosis (MS) episodes. While it is well-established that there is an inverse relationship between serum steroid-levels and decreases of cortical thickness (CT), little is known about the effects of steroid treatment during MS relapses on CT.

Objectives

In this study, we investigated whether CT changes occur in MS patients following steroid treatment after the first clinical episode in MS in a retrospective design. Additionally, we aimed to assess whether such effects were sustained.

Methods

T1-weighted magnetic resonance (MR) images were acquired from 8 MS patients during their first clinical episode (7 females, median age 27 years). At the time of that baseline scan, all patients were within 5 days of onset of prednisolone treatment (1000mg/day i.v.; steroid treatment was stopped after these 5 days). A first follow-up scan was acquired 4 weeks later. To check for sustained effects on CT (post-hoc), a second follow-up scan, 8 weeks after baseline, was acquired. Additionally, data from 8 age- and sex-matched healthy controls (HC) was acquired (baseline and 4 weeks later).

CT maps from all subjects were generated individually and parceled into 68 regions using the Desikan-Killiany atlas. We used a repeated measures analysis of variance to test for significant differences of CT changes between MS and HC over time. Family-wise error-corrected p-values (p_FWER) were calculated using a Monte-Carlo permutation procedure. Since the ANOVA yielded a significant interaction for one region, we investigated post-hoc whether that effect was still observable another four weeks after the first follow-up. To test for this effect, we used a paired t-test to compare mean CT levels of that region within the patient group between 4 and 8 weeks after treatment, as well as baseline vs. 8 weeks after treatment.

Results

The ANOVA showed a significant interaction of group x time for the medial orbitofrontal cortex (mOFC) of the right hemisphere (F = 21.956 , p_FWER = 0.011), with MS patients showing a decrease of mean CT within that region over time. No main effects were observed. A post-hoc paired t-test comparing the CT means within the mOFC at a second follow-up scans eight weeks after baseline revealed no significant difference between follow-up 1 and follow-up 2 (t₇ = -0.9841, p = 0.3578) and approached significance for the comparison between baseline and follow-up 2 (t₇ = 2.3513, p = 0.0510).

Conclusions

Our results provide first evidence that steroid treatment during the first acute episode in MS was associated with cortical thinning in the mOFC, which tended to reverse after eight weeks of steroid-free treatment. Although these results need to be further validated in a larger cohort, our results suggest that steroid treatment potentially associates to atrophy in the medial orbitofrontal cortex; an effect which – if validated – should be taken into account for MS therapy.