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Introduction <p>Amyotrophic Lateral Sclerosis (ALS) affects upper (UMN) and lower (LMN) motor neurons. ALS diagnosis is challenging, especially in predominant LMN phenotypes. Electromyography can disclose LMN damage, while UMN involvement is detectable by clinical examination, with possible support of magnetic resonance imaging (MRI) and transcranial magnetic stimulation. Our aim was to investigate the role of 2-[<sup>18</sup>F]FDG-PET as an UMN biomarker in ALS.</p> Methods <p>In our cross-sectional study, we created an UMN burden score. Performing a multiple regression analysis in SPM12, we evaluated the relationship between UMNBS and brain metabolism. We split ALS cohort based on the UMN burden score median value (group A—under median, group B—above median). We ran a full factorial analysis including group A and B and healthy controls, followed by group comparisons.</p> Results <p>We included 118 ALS patients (group A and B, <i>N</i> = 59), with a median UMN burden score of 9.50 and a left lateralization of UMN signs. We found a negative correlation between motor cortex metabolism and UMN burden score. Comparing each ALS group with healthy controls, we found relative hypometabolism in the left frontal lobe and relative bilateral, right-prevalent hypermetabolism of cerebellum and corticospinal tracts. The relative hypermetabolism in corticospinal tracts was more evident in the group with low UMN signs.</p> Conclusions <p>Motor cortex metabolism reflects UMN burden. Corticospinal tracts’ metabolic changes could provide information about UMN involvement even in patients with predominant LMN phenotype, suggesting a possible role of brain 2-[<sup>18</sup>F]FDG-PET as an UMN biomarker in ALS patients.</p>

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Role of 2-[18F]FDG-PET as a biomarker of upper motor neuron involvement in amyotrophic lateral sclerosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • Sara Cabras,
  • Umberto Manera,
  • Francesca Di Pede,
  • Grazia Zocco,
  • Rosario Vasta,
  • Andrea Novara,
  • Emilio Minerva,
  • Enrico Matteoni,
  • Filippo De Mattei,
  • Giorgio Pellegrino,
  • Maurizio Grassano,
  • Barbara Iazzolino,
  • Francesca Palumbo,
  • Stefano Callegaro,
  • Giulia Polverari,
  • Silvia Daniela Morbelli,
  • Matteo Pardini,
  • Agostino Chiaravalloti,
  • Orazio Schillaci,
  • Klaus Leonard Leenders,
  • Rosalie Vered Kogan,
  • Cristina Moglia,
  • Andrea Calvo,
  • Adriano Chiò,
  • Marco Pagani,
  • Antonio Canosa

摘要

Introduction

Amyotrophic Lateral Sclerosis (ALS) affects upper (UMN) and lower (LMN) motor neurons. ALS diagnosis is challenging, especially in predominant LMN phenotypes. Electromyography can disclose LMN damage, while UMN involvement is detectable by clinical examination, with possible support of magnetic resonance imaging (MRI) and transcranial magnetic stimulation. Our aim was to investigate the role of 2-[18F]FDG-PET as an UMN biomarker in ALS.

Methods

In our cross-sectional study, we created an UMN burden score. Performing a multiple regression analysis in SPM12, we evaluated the relationship between UMNBS and brain metabolism. We split ALS cohort based on the UMN burden score median value (group A—under median, group B—above median). We ran a full factorial analysis including group A and B and healthy controls, followed by group comparisons.

Results

We included 118 ALS patients (group A and B, N = 59), with a median UMN burden score of 9.50 and a left lateralization of UMN signs. We found a negative correlation between motor cortex metabolism and UMN burden score. Comparing each ALS group with healthy controls, we found relative hypometabolism in the left frontal lobe and relative bilateral, right-prevalent hypermetabolism of cerebellum and corticospinal tracts. The relative hypermetabolism in corticospinal tracts was more evident in the group with low UMN signs.

Conclusions

Motor cortex metabolism reflects UMN burden. Corticospinal tracts’ metabolic changes could provide information about UMN involvement even in patients with predominant LMN phenotype, suggesting a possible role of brain 2-[18F]FDG-PET as an UMN biomarker in ALS patients.