IntroductionHereditary spastic paraplegia (HSP) encompasses a diverse group of neurodegenerative disorders that results in significant disability with no curative or disease-modifying treatment. The lack of standardised biomarkers of disease severity has limited the evaluation of potential therapeutic agents. Our aim is to investigate motor evoked potentials (MEPs) as a marker of HSP disease severity.MethodsWe studied 21 subjects (10 male, 11 female; mean age 54.3±13.8 years) with a clinical diagnosis of HSP (10 SPG4, 4 SPG7, 1 SPG3A, 1 SPG 30, 5 genetically undetermined). All patients underwent transcranial magnetic stimulation to measure central motor conduction time (CMCT), resting motor threshold (rMT) and MEP amplitude from the tibialis anterior (TA), abductor hallucis (AH) and abductor digiti minimi (ADM). Clinical disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Pearson correlation coefficient was used to assess correlation between variables, significance was defined as P value<0.05.ResultsTA CMCT was prolonged in 16/21 subjects (76%). AH CMCT was absent in 3/18 subjects (16.7%) and prolonged in 9/18 subjects (50%). ADM CMCT was measured in 19 subjects; all were normal. There was no significant correlation between SPRS scores and MEP amplitude, rMT or CMCT for TA or AH. There was also no significant correlation between these MEP measures and disease duration or patient age. Subgroup analysis of SPG4 HSP (10 subjects) revealed significant correlation between TA and AH CMCT with disease duration (r=0.841, p=0.001; r=0.930, p=0.001) but not SPRS scores.ConclusionLower limb CMCT was absent or prolonged in the majority of subjects. Despite being potentially useful as a diagnostic biomarker for HSP, this study only showed a correlation between lower limb CMCT and disease duration in the SPG4 subgroup. Further genotype-specific studies utilising larger numbers may clarify the relationship between MEP markers and clinical features.
Motor Evoked Potentials in Hereditary Spastic Paraplegia—A Systematic Review