Abstract for presentation at Australian and New Zealand Association of Neurologists Annual Scientific Meeting 2008

Objective: Distal hereditary motor neuronopathy with pyramidal features (dHMNP) clinically resembles amyotrophic lateral sclerosis (ALS) in that upper and lower motor neuron signs are present within the same region, thereby providing a unique opportunity to assess the specificity of cortical hyperexcitability in ALS. Consequently, the present study applied novel excitability techniques to test whether cortical hyperexcitability is specific to ALS. Methods: Cortical excitability studies were undertaken in 5 dHMNP and 50 ALS patients, and the results were compared to 55 normal controls. Results: In dHMNP patients, prolongation of central motor conduction time (dHMNP 8.0±0.7 ms; ALS 4.9±0.3 ms; controls 5.1±0.2 ms, P<0.01) was the most marked abnormality. Short-interval intracortical inhibition (SICI) was significantly reduced in ALS patients (ALS 0.8±0.8%) when compared to dHMNP (5.6±1.1%, P<0.001) and normal controls (8.6±1.1%, P<0.0001). The reduction of SICI was an early abnormality in ALS, accompanied by significant increases in intracortical facilitation and motor evoked potential amplitude along with reduction in cortical silent period duration. Although SICI was reduced in dHMNP compared to controls (P<0.02), this reduction was less marked than in ALS and was a late feature of the disease. Conclusions: The present study has established that cortical hyperexcitability, evident in ALS, was not a prominent feature in dHMNP. Although SICI was mildly reduced in dHMNP, it was a late feature, thereby suggesting that SICI reduction resulted from the disease process. Together, the present study suggests the cortical hyperexcitability is specific to ALS, thereby supporting the hypothesis that cortical hyperexcitability underlies neurodegneration in ALS.