Leptomeningeal enhancement in multiple sclerosis: a focus on patients treated with hematopoietic stem cell transplantation

Abstract

Background: Leptomeningeal enhancement (LME) is considered an MRI marker of leptomeningeal inflammation in inflammatory neurological disorders, including multiple sclerosis (MS). To our knowledge, no disease-modifying therapies (DMTs) have been demonstrated to affect LME number or morphology so far.

Methods: Monocentric study investigating the frequency and number of LME in a cohort of people with (pw)MS who performed a 3 T brain MRI with a standardized protocol (including a post-contrast FLAIR sequence), and exploring the impact of autologous hematopoietic stem cell transplantation (AHSCT) on this marker. In a longitudinal pilot study, consecutive MRIs were also analyzed in a subgroup of pwMS, including patients evaluated both pre- and post-AHSCT.

Results: Fifty-five pwMS were included: 24/55 (44%) had received AHSCT (AHSCT group) and 31 other treatments (CTRL group). At least one LME was identified in 19/55 (35%) cases (42 and 29% in the AHSCT and CTRL groups, respectively; p = 0.405). In the AHSCT group, LME number correlated with age at AHSCT (R = 0.50; p = 0.014), but not with age at post-treatment MRI. In the longitudinal pilot study (n = 8), one LME disappeared following AHSCT in 1/4 patients, whereas LME number was unchanged in the remaining four pwMS from the CTRL group.

Discussion: These results suggest that AHSCT may affect development and persistence of LME, strengthening the indication for early use of effective therapies bioavailable within the central nervous system (CNS), and therefore potentially targeting compartmentalized inflammation.

Keywords: autologous hematopoietic stem cell transplantation; biomarker; chronic inflammation; leptomeningeal enhancement; magnetic resonance imaging; multiple sclerosis; transplant.

Figure 1

Proportion of patients from the AHSCT and CTRL groups who were receiving active treatment with each DMT at the time of MRI (A) or who had received each DMT since MS diagnosis (B). All the patients from the AHSCT group were untreated at the time of MRI, whereas 61% of patients in the CTRL group were receiving treatment with DMTs. No significant differences were observed in treatment history between the two groups, except for a higher proportion of patients from the AHSCT group who had received fingolimod.

Figure 2

Proportion of LME-positive patients in the overall MS cohort and in the AHSCT and CTRL groups, and in patients from each group stratified according to the MS form (relapsing–remitting, RR, or secondary-progressive, SP). RR-MS patients from the AHSCT group tended to higher proportion of LME positivity compared to those in the CTRL group.

Figure 3

Number of LME in the AHSCT and CTRL groups, stratified according to the MS form (relapsing–remitting, RR, or secondary-progressive, SP). Median values are represented by a line.

Figure 4

The disappearance of one LME focus was observed in one patient after AHSCT from the pre-treatment scan [axial (A) and coronal (C)] to the MRI scan taken at 6 months after AHSCT [axial (B) and coronal (D)].