ALS is a rapidly progressive neurodegenerative disorder of the motor neurons with median survival of 3-5 years. The site of disease onset, and the timing of disease onset remain controversial, although
a sudden and catastrophic degeneration of the motor neurons does occur. In this issue of JNNP a though provoking review by Eisen and colleagues suggests a long term pre clinicla period, perhaps stretching beck to the in utero period. In an
accompanying letter, neuronal dysfunction (preceding degeneration) was reported in a zebra fish model. Interestingly, this dysfunction was slowed down by riluzole. The question remains as to whether we are too late by the time the patients present. But then, who should be treated/monitored. The genetic cases, or all relatives of sporadic cases. Clearly there are more answers than questions, although headway has been made, and more research is needed.