Evoked potentials as biomarkers of hereditary spastic paraplegias: A case-control study

Abstract

The Hereditary Spastic Paraplegias (HSP) are a group of genetic diseases that lead to slow deterioration of locomotion. Clinical scales seem to have low sensitivity in detecting disease progression, making the search for additional biomarkers a paramount task. This study aims to evaluate the role of evoked potentials (EPs) as disease biomarkers of HSPs. A single center cross-sectional case-control study was performed, in which 18 individuals with genetic diagnosis of HSP and 21 healthy controls were evaluated. Motor evoked potentials (MEP) obtained with transcranial magnetic stimulation and somatosensory evoked potentials (SSEP) were performed in lower (LL) and upper limbs (UL). Central motor conduction time in lower limbs (CMCT-LL) was prolonged in HSP subjects, with marked reductions in MEP-LL amplitudes when compared to the control group (p<0.001 for both comparisons). CMCT-UL was 3.59ms (95% CI: 0.73 to 6.46; p = 0.015) prolonged and MEP-UL amplitudes were reduced (p = 0.008) in the HSP group. SSEP-LL latencies were prolonged in HSP subjects when compared to controls (p<0.001), with no statistically significant differences for upper limbs (p = 0.147). SSEP-UL and SSEP-LL latencies presented moderate to strong correlations with age at onset (Rho = 0.613, p = 0.012) and disease duration (Rho = 0.835, p<0.001), respectively. Similar results were obtained for the SPG4 subgroups of patients. Motor and somatosensory evoked potentials can adequately differentiate HSP individuals from controls. MEP were severely affected in HSP subjects and SSEP-LL latencies were prolonged, with longer latencies being related to more severe disease. Future longitudinal studies should address if SSEP is a sensitive disease progression biomarker for HSP.