Axonal damage in SPG4 studied

Imaging shows impairment related to severity

Disease severity in SPG4 correlates with reduced fibre density, reduced cross-section of the corticospinal tracts and cortical thinning in the midbrain area (precentral gyrus).

Precentral gyrus shown in red

Objective: SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive retrograde degeneration, or “dying-back” phenomenon, of the corticospinal tract’s longest axons. Neuroimaging studies mainly focus on white matter changes and, although previous studies reported cortical thinning in complicated HSP forms, cortical changes remain unclear in SPG4 patients.

This work aimed to compare changes in white matter microstructure and cortical thickness between 12 SPG4 patients and 22 healthy age-matched controls. We also explore whether white matter alterations are related to cortical thickness and their correlation with clinical symptoms.

Methods: we used fixel-based analysis, an advanced diffusion-weighted imaging technique, and probabilistic tractography of the corticospinal tracts. We also analyzed cortical morphometry using whole-brain surface-based and atlas-based methods in sensorimotor areas.

Results: SPG4 patients showed bilateral involvement in the corticospinal tracts; this was more intense in the distal portion than in the upper segments and was associated with the degree of clinical impairment. We found a significant correlation between disease severity and fiber density and cross-section of the corticospinal tracts. Furthermore, corticospinal tract changes were significantly correlated with bilateral cortical thinning in the precentral gyrus in SPG4 patients.

Conclusions: Our data point to axonal damage of the corticospinal motor neurons in SPG4 patients might be related to cortical thinning in motor regions.

SOURCE:  Amyotroph Lateral Scler Frontotemporal Degener. 2021 Aug 16;1-10. doi: 10.1080/21678421.2021.1962353. Online ahead of print. PMID: 34396852

Corticospinal tract and motor cortex degeneration in pure hereditary spastic paraparesis type 4 (SPG4)

Francisco J Navas-Sánchez  1   2 Daniel Martín De Blas  2 Alberto Fernández-Pena  2 Yasser Alemán-Gómez  3   4   5 Agustín Lage-Castellanos  6 Luis Marcos-Vidal  1   2   7 Juan A Guzmán-De-Villoria  1   2   8 Irene Catalina  2   9 Laura Lillo  10   11 José L Muñoz-Blanco  2   9 Andrés Ordoñez -Ugalde  12   13   14 Beatriz Quintáns  15   16   17 María-Jesús Sobrido  15   18 Susanna Carmona  1   2 Francisco Grandas  2   9 Manuel Desco  1   2   7   19

1. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.

2. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

3. Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland.

4. Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.

5. Centre d’Imagerie BioMédicale (CIBM), Medical Image Analysis Laboratory (MIAL), Lausanne, Switzerland.

6. Departamento de Neuroestadística, Centro de Neurociencias de Cuba, La Habana, Cuba.

7. Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.

8. Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

9. Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

10. Servicio de Neurología, Hospital Ruber Internacional, Madrid, Spain.

11. Servicio de Neurología, Hospital Universitario Fundación Alcorcón, Madrid, Spain.

12 Laboratorio Biomolecular, Cuenca, Ecuador.

13 Unidad de Genética y Molecular, Hospital de Especialidades José Carrasco Arteaga, Cuenca, Ecuador.

14. Neurogenetics Group, FPGMX-IDIS, Santiago de Compostela, Spain.

15. Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.

16. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-U711), Madrid, Spain.

17. Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.

18. Hospital Clínico Universitario de A Coruña, SERGAS, A Coruña, Spain

19. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.

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