63.: Cortical dysfunction in hereditary spastic paraparesis patients with the spastin mutation

Abstract

In autosomal dominant hereditary spastic paraplegia (HSP), mutations in the spastin (SPG4) gene account for 45% of all cases. The key diagnostic clinical findings are lower limb spasticity, hyperreflexia and extensor plantar responses. The main neuropathological finding in HSP is axonal degeneration in the terminal portions of the long descending and ascending tracts in the spinal cord. Current hypothesis suggest impairment of axonal transport or disturbance of mitochondrial function. We utilised the threshold tracking transcranial magnetic stimulation (TTTMS) technique to evaluate if cortical abnormalities may coexist in these patients. Cortical excitability studies were undertaken on 12 HSP patients with the SPG4 mutation (five males and seven females, mean age 56 years). Patients were compared with age-matched controls. The mean spastic paraplegia rating scale was 17.3 ± 3.0 and the mean upper motor neuron score was 13.5 ± 0.5. Short-interval intracortical inhibition was significantly reduced in HSP patients when compared to controls (HSP 5.0 ± 1.6%; controls 11.8 ± 1.0%, p p p p