Calcium accumulation or iron deposition: Delving into the temporal sequence of amyotrophic lateral sclerosis pathophysiology in the primary motor cortex

• Published in: Ibrain 2024-06, Vol.10 (3), p.375-377
• Main Authors: Ghaderi, Sadegh, Mohammadi, Sana, Fatehi, Farzad
• Format: Article
• Language: English
• Subjects: ALS; calcium; iron; Letter; primary motor cortex; QSM
• ISSN: 2313-1934; 2769-2795; 2769-2795
• DOI: 10.1002/ibra.12168

Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, but an in vivo understanding of its early pathology remains limited. A recent study used topographic layer imaging to investigate iron and calcium accumulation in the primary motor cortex (M1) of patients with ALS compared with controls. Despite the preserved cortical thickness, ALS patients showed increased iron in layer 6 and calcium accumulation in layer 5a and the superficial layer. Calcium accumulation was particularly prominent in the low‐myelin borders, potentially preceding the demyelination. This study reveals a novel in vivo pathology in ALS, suggesting that calcium dysregulation may precede iron accumulation and contribute to early M1 cell degeneration. Further investigation using quantitative susceptibility mapping and complementary techniques, such as diffusion kurtosis imaging, along with ultrahigh‐field magnetic resonance imaging, into the role of calcium and early intervention strategies is warranted. Amyotrophic lateral sclerosis (ALS) causes motor and nonmotor neuron degeneration, and the understanding of its early pathology is limited. A recent study used imaging to investigate iron and calcium accumulation in the primary motor cortex (M1) of ALS patients compared with controls. Despite preserved cortical thickness, ALS patients showed increased iron in layer 6 and calcium accumulation in layer 5a and the superficial layer. Calcium accumulation was prominent in low‐myelin borders, potentially preceding demyelination. This study reveals a novel pathology in ALS, suggesting that calcium dysregulation may precede iron accumulation and contribute to early M1 cell degeneration. Further research using quantitative susceptibility mapping and additional methods such as diffusion kurtosis imaging, in combination with ultrahigh‐field magnetic resonance imaging, is necessary to explore the impact of calcium and potential early intervention approaches.