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Association between brain and upper cervical spinal cord atrophy assessed by MRI and disease aggressiveness in amyotrophic lateral sclerosis

  • Advanced Neuroimaging
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Abstract

Purpose

To study the relative contributions of brain and upper cervical spinal cord compartmental atrophy to disease aggressiveness in amyotrophic lateral sclerosis (ALS).

Methods

Twenty-nine ALS patients and 24 age- and gender-matched healthy controls (HC) were recruited. Disease duration and the Revised-ALS Functional Rating Scale (ALSFRS-R) at baseline, 3- and 6-months follow-up were assessed. Patients were clinically differentiated into fast (n=13) and slow (n=16) progressors according to their ALSFRS-R progression rate. Brain grey (GM) and white matter, brainstem sub-structures volumes and spinal cord cross-sectional area (SC-CSA) at C1-C2 vertebral levels were measured from a 3D-T1-weighted MRI.

Results

Fast progressors showed significant GM, medulla oblongata and SC atrophy compared to HC (p<0.001, p=0.013 and p=0.008) and significant GM atrophy compared to slow progressors (p=0.008). GM volume correlated with the ALSFRS-R progression rate (Rho/p=-0.487/0.007), the ALSFRS-R at 3-months (Rho/p=0.622/0.002), and ALSFRS-R at 6-months (Rho/p=0.407/0.039). Medulla oblongata volume and SC-CSA correlated with the ALSFRS-R at 3-months (Rho/p=0.510/0.015 and Rho/p=0.479/0.024). MRI measures showed high performance to discriminate between fast and slow progressors.

Conclusion

Our study suggests an association between compartmental atrophy and disease aggressiveness. This result is consistent with the combination of upper and lower motor neuron degeneration as the main driver of disease worsening and severity in ALS. Our study highlights the potential of brain and spinal cord atrophy measured by MRI as biomarker of disease aggressiveness signature.

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Funding

This research was funded by APHM (AORC Junior 2014 program), ARSLA (Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres maladies du motoneurone) and FRC (Fédération pour la Recherche sur le Cerveau).

Author information

Authors and Affiliations

  1. Aix Marseille Univ, CNRS, CRMBM, Marseille, France

    Mohamed Mounir El Mendili, Annie Verschueren, Jean-Philippe Ranjeva, Maxime Guye, Wafaa Zaaraoui & Aude-Marie Grapperon

  2. APHM, Hopital de la Timone, CEMEREM, Marseille, France

    Mohamed Mounir El Mendili, Annie Verschueren, Jean-Philippe Ranjeva, Maxime Guye, Wafaa Zaaraoui & Aude-Marie Grapperon

  3. Centre de Résonance Magnétique Biologique et Médicale, CRMBM-CEMEREM, UMR 7339 CNRS - Aix–Marseille Université, 27 Bd Jean Moulin, 13005, Marseille, France

    Mohamed Mounir El Mendili

  4. APHM, Hôpital de la Timone, Referral Centre for Neuromuscular Diseases and ALS, Marseille, France

    Annie Verschueren, Shahram Attarian & Aude-Marie Grapperon

  5. Aix Marseille Univ, INSERM, MMG, Marseille, France

    Shahram Attarian

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  1. Mohamed Mounir El Mendili
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Contributions

All authors contributed to the study conception and design. Subjects recruitment was performed by Wafaa Zaaraoui, Aude-Marie GRAPPERON, Annie VERSCHUEREN and Shahram ATTARIAN. Material preparation, data collection and analysis were performed by Wafaa Zaaraoui, Aude-Marie GRAPPERON, Jean-Philippe RANJEVA and Mohamed Mounir EL MENDILI. The first draft of the manuscript was written by Wafaa Zaaraoui, Aude-Marie GRAPPERON, and Mohamed Mounir EL MENDILI and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mohamed Mounir El Mendili.

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El Mendili, M.M., Verschueren, A., Ranjeva, JP. et al. Association between brain and upper cervical spinal cord atrophy assessed by MRI and disease aggressiveness in amyotrophic lateral sclerosis. Neuroradiology 65, 1395–1403 (2023). https://doi.org/10.1007/s00234-023-03191-0

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