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<p>Four different subtypes of amyotrophic lateral sclerosis (ALS) were identified based on their clinical and magnetic resonance imaging (MRI) findings, including: (a) classic ALS (ALS-Cl) (b) upper motor neuron (UMN)-predominant ALS with corticospinal tract (CST) hyperintensity (ALS-CST+), (c) UMN-predominant ALS without CST hyperintensity (ALS-CST–), and (d) ALS with frontotemporal dementia (ALS-FTD). These phenotypes also showed differences in symptom duration, disease progression rate, revised ALS functional rating scale score and El Escorial score.</p><p>Network diffusion model (NDM) is a computational approach that can identify disease epicenters based on brain gray matter (GM) atrophy and white matter (WM) structural connectome from cross-sectional MRI. Although previous NDM MRI studies have considered ALS patients as a single group, we examined whether the above-mentioned phenotypes display subgroup-specific site of disease onset, and whether the latter differs between positron emission tomography -revealed hypo- and hypermetabolic brain regions in ALS-FTD patients. Clinical evaluation and cross-sectional MRI of 83 patients with differing presentations of ALS were assigned into one of four subgroups, and NDM applied to the data.</p><p>Both ALS-CST + and ALS-CST– subgroups showed the putamen as epicenter for GM atrophy and superior frontal gyrus (orbital part) as epicenter for WM disconnection. The ALS-Cl subgroup also showed the putamen as epicenter for GM degeneration but the inferior parietal gyrus (excluding supramarginal and angular gyri) for WM disconnection, the latter overlapping with ALS-FTD patients. However, epicenters for structural and functional GM degeneration in the ALS-FTD subgroup were different. These results suggest differential patterns of GM and WM degeneration onset between the four ALS subgroups.</p>

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Diffusion network model analysis of multimodal neuroimaging reveals differential patterns of brain disease propagation in four subgroups of ALS patients

  • 期刊论文

  • 发表日期：

    2026年3月30日

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  • Venkateswaran Rajagopalan,
  • Erik P. Pioro

摘要

Four different subtypes of amyotrophic lateral sclerosis (ALS) were identified based on their clinical and magnetic resonance imaging (MRI) findings, including: (a) classic ALS (ALS-Cl) (b) upper motor neuron (UMN)-predominant ALS with corticospinal tract (CST) hyperintensity (ALS-CST+), (c) UMN-predominant ALS without CST hyperintensity (ALS-CST–), and (d) ALS with frontotemporal dementia (ALS-FTD). These phenotypes also showed differences in symptom duration, disease progression rate, revised ALS functional rating scale score and El Escorial score.

Network diffusion model (NDM) is a computational approach that can identify disease epicenters based on brain gray matter (GM) atrophy and white matter (WM) structural connectome from cross-sectional MRI. Although previous NDM MRI studies have considered ALS patients as a single group, we examined whether the above-mentioned phenotypes display subgroup-specific site of disease onset, and whether the latter differs between positron emission tomography -revealed hypo- and hypermetabolic brain regions in ALS-FTD patients. Clinical evaluation and cross-sectional MRI of 83 patients with differing presentations of ALS were assigned into one of four subgroups, and NDM applied to the data.

Both ALS-CST + and ALS-CST– subgroups showed the putamen as epicenter for GM atrophy and superior frontal gyrus (orbital part) as epicenter for WM disconnection. The ALS-Cl subgroup also showed the putamen as epicenter for GM degeneration but the inferior parietal gyrus (excluding supramarginal and angular gyri) for WM disconnection, the latter overlapping with ALS-FTD patients. However, epicenters for structural and functional GM degeneration in the ALS-FTD subgroup were different. These results suggest differential patterns of GM and WM degeneration onset between the four ALS subgroups.