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Tract-specific damage at spinal cord level in pure hereditary spastic paraplegia type 4: a diffusion tensor imaging study

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Abstract

Background

SPG4 is a subtype of hereditary spastic paraplegia (HSP), an upper motor neuron disorder characterized by axonal degeneration of the corticospinal tracts and the fasciculus gracilis. The few neuroimaging studies that have focused on the spinal cord in HSP are based mainly on the analysis of structural characteristics.

Methods

We assessed diffusion-related characteristics of the spinal cord using diffusion tensor imaging (DTI), as well as structural and shape-related properties in 12 SPG4 patients and 14 controls. We used linear mixed effects models up to T3 in order to analyze the global effects of 'group' and 'clinical data' on structural and diffusion data. For DTI, we carried out a region of interest (ROI) analysis in native space for the whole spinal cord, the anterior and lateral funiculi, and the dorsal columns. We also performed a voxelwise analysis of the spinal cord to study local diffusion-related changes.

Results

A reduced cross-sectional area was observed in the cervical region of SPG4 patients, with significant anteroposterior flattening. DTI analyses revealed significantly decreased fractional anisotropy (FA) and increased radial diffusivity at all the cervical and thoracic levels, particularly in the lateral funiculi and dorsal columns. The FA changes in SPG4 patients were significantly related to disease severity, measured as the Spastic Paraplegia Rating Scale score.

Conclusions

Our results in SPG4 indicate tract-specific axonal damage at the level of the cervical and thoracic spinal cord. This finding is correlated with the degree of motor disability.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

All the authors wish to express our appreciation for the invaluable contribution of the late Dr. Santiago Reig to this study. We are grateful to the patients for their collaboration and the Asociación Española de Paraparesia Espástica Familiar (AEPEF) for their support with patient recruitment.

Funding

This work was supported by Ministerio de Ciencia, Innovación y Universidades and by Instituto de Salud Carlos III projects PS09/01830, PS09/01685, and PS09/00839. The ASPIDE project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 801091. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV‐2015‐0505). Susanna Carmona is funded by Instituto de Salud Carlos III, Miguel Servet Type I research contract (CP16/00096).

Author information

Author notes

  1. Francisco Grandas and Manuel Desco shared co-last authorship.

Authors and Affiliations

  1. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Dr Esquerdo 46, 28007, Madrid, Spain

    Francisco J. Navas-Sánchez, Luis Marcos-Vidal, Daniel Martín de Blas, Alberto Fernández-Pena, Juan A. Guzmán-de-Villoria, Susanna Carmona & Manuel Desco

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

    Francisco J. Navas-Sánchez, Luis Marcos-Vidal, Daniel Martín de Blas, Alberto Fernández-Pena, Juan A. Guzmán-de-Villoria, Julia Romero, Irene Catalina, José L. Muñoz-Blanco, Susanna Carmona, Francisco Grandas & Manuel Desco

  3. Departamento de Bioingeniería E Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain

    Luis Marcos-Vidal, Daniel Martín de Blas, Alberto Fernández-Pena & Manuel Desco

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

    Yasser Alemán-Gómez

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

    Yasser Alemán-Gómez

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

    Yasser Alemán-Gómez

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

    Juan A. Guzmán-de-Villoria & Julia Romero

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

    Irene Catalina, José L. Muñoz-Blanco & Francisco Grandas

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

    Laura Lillo

  10. Instituto de Investigación Sanitaria, Hospital Clínico Universitario, Santiago de Compostela, Spain

    Andrés Ordoñez-Ugalde, Beatriz Quintáns & María-Jesús Sobrido

  11. Laboratorio Biomolecular, Cuenca, Ecuador

    Andrés Ordoñez-Ugalde

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

    Andrés Ordoñez-Ugalde

  13. Instituto de Investigación Biomédica, Hospital Clínico Universitario de A Coruña, SERGAS, A Coruña, Spain

    María-Jesús Sobrido

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

    Beatriz Quintáns

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

    Beatriz Quintáns

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

    Manuel Desco

Authors
  1. Francisco J. Navas-Sánchez
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  2. Luis Marcos-Vidal
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  3. Daniel Martín de Blas
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  8. Irene Catalina
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  14. Susanna Carmona
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  15. Francisco Grandas
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  16. Manuel Desco
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Contributions

1A. Design of the work; 1B. Acquisition and analysis, 1C. Interpretation of data for the work; 2. Drafting the work or revising it critically for important intellectual content; 3. Final approval of the version to be published; 4. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved). FJNS: 1A, 1B, 1C, 2, 3, 4; LMV: 1B, 1C, 3, 4; DMdB: 1B, 2, 3, 4; AFP: 1B, 2, 3, 4; YAG: 1A, 1B 3, 4; JAGdV: 1B, 3, 4; JR: 1B, 3, 4; IC: 1B, 3, 4; LL: 1B, 3, 4; JLMB: 1B, 3, 4; AOU: 1B, 3, 4; BQ: 1B, 3, 4; MJS: 1A, 1B, 3, 4; SC: 1C, 2, 3, 4; FG: 1A, 1C, 2, 3, 4; MD: 1A, 1C, 2, 3, 4.

Corresponding author

Correspondence to Francisco J. Navas-Sánchez.

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None of the authors have any conflicts of interest to disclose.

Research involving human participants

The study was approved by the Ethics and Clinical Research Board of Hospital Gregorio Marañón.

Informed consent

Written informed consent was obtained from all patients before they participated in the study.

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Navas-Sánchez, F.J., Marcos-Vidal, L., de Blas, D.M. et al. Tract-specific damage at spinal cord level in pure hereditary spastic paraplegia type 4: a diffusion tensor imaging study. J Neurol 269, 3189–3203 (2022). https://doi.org/10.1007/s00415-021-10933-8

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