16.: Cortical excitability in hereditary spastic paraparesis patients with SPAST mutations

Abstract

In autosomal dominant hereditary spastic paraplegia (HSP), mutations in the SPAST (SPG4) gene account for 45% of all patients. The key diagnostic clinical findings are that of lower limb spasticity, hyperreflexia and extensor plantar responses. The main neuropathological finding in HSP is of axonal degeneration in the terminal portions of the long descending and ascending tracts in the spinal cord. The current hypothesis suggests impairment of axonal transport or disturbance of mitochondrial function. We utilised the threshold tracking transcranial magnetic stimulation 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 (SICI) was not significantly reduced in HSP patients when compared to controls (HSP 9.1 ± 1.5%; controls 11.8 ± 1.0%, p = 0.09). The cortical silent period duration was significantly reduced (HSP 192.9 ± 11.5 ms; controls 214.2 ± 3.9, p = 0.05). Resting motor threshold was significantly reduced amongst HSP patients (HSP 51.8 ± 2.2%; controls 60.3 ± 1.4%, p