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

BackgroundThe 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 dataO_LILeptomeningeal enhancement (LME) is a nonspecific imaging feature present across many neurological disorders, including neoplasm, infection, and primary neuroinflammation. C_LIO_LIThe presence of LME is associated with worse clinical and imaging outcomes in multiple sclerosis, justifying its ascertainment in clinical practice. C_LIO_LINeuroinflammatory animal models can be used to further investigate the pathophysiology of LME, including its pathological tissue signature and/or its association with cortical pathology. C_LI