ObjectivesThe lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation.MethodsIn a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis.ResultsOur meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2*-hypointensitites, also called “motor band sign”, are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40–3.49) and 10.85 (95%-CI: 3.74–31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns.ConclusionsAlthough CST T2-hyperintensities and the “motor band sign” are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682.

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Background and objectivesAnimal models for motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) are commonly used in preclinical research. However, it is insufficiently understood how much findings from these model systems can be translated to humans. Thus, we aimed at systematically assessing the translational value of MND animal models to probe their external validity with regards to magnetic resonance imaging (MRI) features.MethodsIn a comprehensive literature search in PubMed and Embase, we retrieved 201 unique publications of which 34 were deemed eligible for qualitative synthesis including risk of bias assessment.ResultsALS animal models can indeed present with human ALS neuroimaging features: Similar to the human paradigm, (regional) brain and spinal cord atrophy as well as signal changes in motor systems are commonly observed in ALS animal models. Blood-brain barrier breakdown seems to be more specific to ALS models, at least in the imaging domain. It is noteworthy that the G93A-SOD1 model, mimicking a rare clinical genotype, was the most frequently used ALS proxy.ConclusionsOur systematic review provides high-grade evidence that preclinical ALS models indeed show imaging features highly reminiscent of human ALS assigning them a high external validity in this domain. This opposes the high attrition of drugs during bench-to-bedside translation and thus raises concerns that phenotypic reproducibility does not necessarily render an animal model appropriate for drug development. These findings emphasize a careful application of these model systems for ALS therapy development thereby benefiting refinement of animal experiments.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022373146.

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