Leptomeningeal enhancement in multiple sclerosis and other neurological diseases: A systematic review and Meta-Analysis

The lack of systematic evidence on leptomeningeal enhancement (LME) on MRI in neurological diseases, including multiple sclerosis (MS), hampers its interpretation in clinical routine and research settings. To perform a systematic review and meta-analysis of MRI LME in MS and other neurological diseases. In a comprehensive literature search in Medline, Scopus, and Embase, out of 2292 publications, 459 records assessing LME in neurological diseases were eligible for qualitative synthesis. Of these, 135 were included in a random-effects model meta-analysis with subgroup analyses for MS. Of eligible publications, 161 investigated LME in neoplastic neurological (n = 2392), 91 in neuroinfectious (n = 1890), and 75 in primary neuroinflammatory diseases (n = 4038). The LME-proportions for these disease classes were 0.47 [95%-CI: 0.37–0.57], 0.59 [95%-CI: 0.47–0.69], and 0.26 [95%-CI: 0.20–0.35], respectively. In a subgroup analysis comprising 1605 MS cases, LME proportion was 0.30 [95%-CI 0.21–0.42] with lower proportions in relapsing-remitting (0.19 [95%-CI 0.13–0.27]) compared to progressive MS (0.39 [95%-CI 0.30–0.49], p = 0.002) and higher proportions in studies imaging at 7 T (0.79 [95%-CI 0.64–0.89]) compared to lower field strengths (0.21 [95%-CI 0.15–0.29], p < 0.001). LME in MS was associated with longer disease duration (mean difference 2.2 years [95%-CI 0.2–4.2], p = 0.03), higher Expanded Disability Status Scale (mean difference 0.6 points [95%-CI 0.2–1.0], p = 0.006), higher T1 (mean difference 1.6 ml [95%-CI 0.1–3.0], p = 0.04) and T2 lesion load (mean difference 5.9 ml [95%-CI 3.2–8.6], p < 0.001), and lower cortical volume (mean difference −21.3 ml [95%-CI −34.7–-7.9], p = 0.002). Our study provides high-grade evidence for the substantial presence of LME in MS and a comprehensive panel of other neurological diseases. Our data could facilitate differential diagnosis of LME in clinical settings. Additionally, our meta-analysis corroborates that LME is associated with key clinical and imaging features of MS. PROSPERO No: CRD42021235026.