Structural Magnetic Resonance Imaging Findings and Histopathological Correlations in Human and Animal Motor Neuron Diseases – A Systematic Review and Meta-Analysis

Abstract

Background: The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) hampers the diagnostic utility of magnetic resonance imaging (MRI) in the clinical setting. Moreover, it is unknown how well MND animal models mimic actual human neuroimaging features.Objective: To perform a systematic review and meta-analysis of MRI features in MND and corresponding animal models including their histopathological correlation.Methods: In a comprehensive literature search in Medline, Scopus, and Embase, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. Of these, 21 records were included in a random effect model meta-analysis. For the animal systematic review, out of 175 unique publications, 33 records assessed neuroimaging findings in MND animal models. Data mining techniques were exploited for risk of bias assessment.Results: T2-hyperintensities along the corticospinal tract as well as motor cortex T2*-hypointensities, also termed the “motor band sign”, were among the most commonly assessed imaging biomarkers. Our meta-analysis shows that both T2-hyperintensities along the corticospinal tracts and the motor band sign more commonly occur in ALS patients compared to controls (Odds ratio 2.21 [95%-CI: 1.40-3.49] and 10.85 [95%-CI: 3.74-31.44], respectively). Evidence from a limited number of studies suggest these two imaging findings to correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology. Whole brain or regional central nervous system (CNS) atrophy was also frequently assessed. Clinical MND phenotypes such as ALS versus ALS-frontotemporal dementia seem to present with distinct CNS atrophy patterns. Furthermore, certain MRI imaging findings in MND animal models such as brain volume loss show partial resemblance with corresponding human imaging features.Conclusions: Multiple corroborating studies support the notion that MND in humans can be distinguished based on certain MRI features, which also correlate to neuropathological findings. In addition, there is also some overlap with findings in animal MND models. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases. Further studies are needed to address the value of MRI for a more exact definition of MND subtypes and prognosticating the disease course.Trial registration number: CRD42020182682