Cramps and spasticity impair quality of life and function in patients with motor neuron diseases, and there are no proven treatments for these problems. We conducted a pilot trial to determine if treatment with levetiracetam was associated with a reduction in cramp severity, cramp frequency, tonic or phasic spasticity. We used an open-label repeated measures pilot trial of 20 patients, comparing cramp and spasticity scores over a 3-month baseline versus nine months on treatment. Cramp and spasticity scores were stable over a 3-month baseline. Shortly after starting levetiracetam, there was a significant reduction in cramp severity and frequency, which persisted for the duration of this year-long study. There was also a reduction in phasic but not tonic spasticity. Levetiracetam was well tolerated. Our results justify a placebo-controlled study of levetiracetam for treatment of cramps and spasticity in patients with motor neuron diseases, and suggest that this can be accomplished with a small number of subjects followed for a short time.