This research project will provide novel and unique approach and data on spinal functional topography, structural and functional organization of the spinal motor output and spinal cord rhythmogenesis in individuals with hereditary spastic paraplegia (HSP) and its progression, thus providing spinal biomarkers of this genetic disease.
Originally considered to be caused by damage to the CNS, the potential involvement of the spinal cord circuitry impairment in HSP genesis has received little attention, even though a part of sensorimotor abnormalities is attributable to the impaired state of the spinal circuitry. The rationale and novelty of this project is the following: if the state of the spinal cord is impaired, it should be controlled differently by the descending pathways, which in turn would enhance the reorganization and involvement of the supraspinal structures to compensate for these abnormalities. These reciprocal spinal-supraspinal compensatory mechanisms create a risk of irreversible plastic changes in the state of locomotor circuitry during progression of the disease. Therefore, a better
knowledge about what happens in HSP at the spinal level is critical for both gait and motor function evaluation and rehabilitation.
Specific gait impairments in HSP is an essential concern. We will test whether locomotor impairments are associated with impairment in the rhythmogenesis capacity of the spinal circuitry and segmental spinal reflexes, that we will assess by the proposed methodology and correlate them with genotype. The knowledge collected in
the project has true chances of becoming a landmark in the field of spinal motor impairments in HSP as well as a significant contribution to the understanding the spinal cord mechanisms and connectivity in this genetic disease. This project has immediate clinical outcomes as a new method for evaluation and prognosis of gait disturbances in individuals with HSP, as well as for gait rehabilitation
