Potential biomarker of disease progression
Significant changes in the structure of the thalamus could be an imaging biomarker of disease progression in pure HSP.
A significant reduction in the volume of the thalamus along with a deformity in shape has been found in this Spanish study of 12 people with pure SPG4 HSP. Significant correlations were also found between the deformity in the thalamus and clinical scores on the SP Rating Scale plus disease duration.
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 spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract.
In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls.
We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volume bilaterally, as well as an inward deformation, mainly in the sensory-motor thalamic regions in patients with pure HSP and a mutation in SPG4. We also observed a significant negative correlation between the shape of the thalamus and clinical scores (the Spastic Paraplegia Rating Scale score and disease duration). Moreover, we found a ‘Group × Age’ interaction that was closely related to the severity of the disease. No differences in volume or in shape were found in the remaining subcortical structures studied.
Our results suggest that changes in structure of the thalamus could be an imaging biomarker of disease progression in pHSP.
SOURCE: J Neurol. 2021 Jan 28. doi: 10.1007/s00415-020-10387-4. Online ahead of print. PMID: 33507371
Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4
Francisco J Navas-Sánchez 1 2 , Alberto Fernández-Pena 3 , Daniel Martín de Blas 3 , Yasser Alemán-Gómez 4 5 6 , Luís Marcos-Vidal 3 7 6 , Juan A Guzmán-de-Villoria 3 7 8 , Pilar Fernández-García 9 , Julia Romero 3 8 , Irene Catalina 10 , Laura Lillo 11 12 , José L Muñoz-Blanco 10 , Andrés Ordoñez-Ugalde 13 14 15 , Beatriz Quintáns 16 17 18 , Julio Pardo 19 , María-Jesús Sobrido 16 20 , Susanna Carmona 3 7 , Francisco Grandas # 10 , Manuel Desco # 3 7 21 22
1 Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
2 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
3 Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
4 Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland.
5 Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
6 Medical Image Analysis Laboratory (MIAL), Centre D’Imagerie BioMédicale (CIBM), Lausanne, Switzerland.
7 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
8 Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
9 Hospital Madrid Montepríncipe, Madrid, Spain.
10 Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
11 Hospital Ruber Internacional, Servicio de Neurología, Madrid, Spain.
12 Hospital Universitario Fundación Alcorcón, Servicio de Neurología Alcorcón, Madrid, Spain.
13 Laboratorio Biomolecular, Cuenca, Ecuador.
14 Unidad de Genética y Molecular, Hospital de Especialidades José Carrasco Arteaga, Cuenca, Ecuador.
15 Neurogenetics Group, FPGMX-IDIS, Santiago de Compostela, Spain.
16 Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
17 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-U711), Madrid, Spain.
18 Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
19 Departamento de Neurología, Hospital Clínico Universitario de Santiago de Compostela, A Coruña, Santiago de Compostela, Spain.
20 Hospital Clínico Universitario de A Coruña, SERGAS, Santiago de Compostela, Spain.
21 Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain.
22 Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
# Contributed equally.