Leptomeningeal Enhancement in Multiple Sclerosis and Other Neurological Diseases: A Systematic Review and Meta-Analysis

Abstract

AbstractBackgroundThe 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.PurposeTo perform a systematic review and meta-analysis of MRI LME in MS and other neurological diseases.Materials and MethodsIn 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.ResultsOf 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 7T (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 1.6ml [95%-CI 0.1–3.0], p=0.04) and T2 lesion load (mean difference 5.9ml [95%-CI 3.2–8.6], p<0.001), and lower cortical volume (mean difference −21.3ml [95%-CI −34.7–-7.9], p=0.002).ConclusionsOur 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.Summary statementOur systematic review and meta-analysis synthesize leptomeningeal enhancement proportions across a comprehensive panel of neurological diseases, including multiple sclerosis, and assesses its prognostic value in multiple sclerosis.Summary dataLeptomeningeal enhancement (LME) is a nonspecific imaging feature present across many neurological disorders, including neoplasm, infection, and primary neuroinflammation.The presence of LME is associated with worse clinical and imaging outcomes in multiple sclerosis, justifying its ascertainment in clinical practice.Neuroinflammatory animal models can be used to further investigate the pathophysiology of LME, including its pathological tissue signature and/or its association with cortical pathology.