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. 2021 Jul;31(7):5272-5280.
doi: 10.1007/s00330-020-07547-5. Epub 2021 Jan 5.

Amyotrophic lateral sclerosis phenotypes significantly differ in terms of magnetic susceptibility properties of the precentral cortex

Giorgio Conte #  1 , Valeria Elisa Contarino #  1 , Silvia Casale  2 , Claudia Morelli  3 , Sara Sbaraini  4 , Elisa Scola  1 , Francesca Trogu  3   5 , Silvia Siggillino  1 , Claudia Maria Cinnante  1 , Luca Caschera  1 , Francesco Maria Lo Russo  1 , Fabio Maria Triulzi  1   5 , Vincenzo Silani  3   5
Affiliations

Amyotrophic lateral sclerosis phenotypes significantly differ in terms of magnetic susceptibility properties of the precentral cortex

Giorgio Conte et al. Eur Radiol. 2021 Jul.

Abstract

Objectives: The aim of our study was to investigate whether the magnetic susceptibility varies according to the amyotrophic lateral sclerosis (ALS) phenotypes based on the predominance of upper motor neuron (UMN)/lower motor neuron (LMN) impairment.

Methods: We retrospectively collected imaging and clinical data of 47 ALS patients (12 with UMN predominance (UMN-ALS), 16 with LMN predominance (LMN-ALS), and 19 with no clinically defined predominance (Np-ALS)). We further enrolled 23 healthy controls (HC) and 15 ALS mimics (ALS-Mim). These participants underwent brain 3-T magnetic resonance imaging (3-T MRI) with T1-weighted and gradient-echo multi-echo sequences. Automatic segmentation and quantitative susceptibility mapping (QSM) were performed. The skewness of the susceptibility values in the precentral cortex (SuscSKEW) was automatically computed, compared among the groups, and correlated to the clinical variables.

Results: The Kruskal-Wallis test showed significant differences in terms of SuscSKEW among groups (χ2(3) = 24.2, p < 0.001), and pairwise tests showed that SuscSKEW was higher in UMN-ALS compared to those in LMN-ALS (p < 0.001), HC (p < 0.001), Np-ALS (p = 0.012), and ALS-Mim (p < 0.001). SuscSKEW was highly correlated with the Penn UMN score (Spearman's rho 0.612, p < 0.001).

Conclusion: This study demonstrates that the clinical ALS phenotypes based on UMN/LMN sign predominance significantly differ in terms of magnetic susceptibility properties of the precentral cortex. Combined MRI-histopathology investigations are strongly encouraged to confirm whether this evidence is due to iron overload in UMN-ALS, unlike in LMN-ALS.

Key points: • Magnetic susceptibility in the precentral cortex reflects the prevalence of UMN/LMN impairment in the clinical ALS phenotypes. • The degree of UMN/LMN impairment might be well described by the automatically derived measure of SuscSKEW in the precentral cortex. • Increased SuscSKEW in the precentral cortex is more relevant in UMN-ALS patients compared to those in Np-ALS and LMN-ALS patients.

Keywords: Amyotrophic lateral sclerosis; Magnetic resonance imaging; Motor cortex; Motor neuron disease.

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References

    1. Ludolph A, Drory V, Hardiman O et al (2015) A revision of the El Escorial criteria - 2015. Amyotroph Lateral Scler Frontotemporal Degener 16:291–292. https://doi.org/10.3109/21678421.2015.1049183 - DOI - PubMed
    1. Al-Chalabi A, Hardiman O, Kiernan MC, Chiò A, Rix-Brooks B, van den Berg LH (2016) Amyotrophic lateral sclerosis: moving towards a new classification system. Lancet Neurol 15:1182–1194
    1. Costagli M, Donatelli G, Biagi L et al (2016) Magnetic susceptibility in the deep layers of the primary motor cortex in amyotrophic lateral sclerosis. Neuroimage Clin 12:965–969. https://doi.org/10.1016/j.nicl.2016.04.011 - DOI - PubMed
    1. Kwan JY, Jeong SY, Van Gelderen P et al (2012) Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology. PLoS One 7:e35241. https://doi.org/10.1371/journal.pone.0035241 - DOI - PubMed
    1. Adachi Y, Sato N, Saito Y et al (2015) Usefulness of SWI for the detection of iron in the motor cortex in amyotrophic lateral sclerosis. J Neuroimaging 25:443–451 - DOI

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