We have previously proposed a serotonergic hypothesis for
cerebellar ataxia and mentioned that the levorotatory form of
5-hydroxytryptophan, a
serotonin precursor, is partially active in subtypes of
cerebellar ataxia, including cerebellar cortical
atrophy (CCA). It has been demonstrated that 5-HT1A serotonergic receptors play an important role in the control of Purkinje cells discharges and in the inhibition of the release of
glutamate by cerebellar glutamatergic terminals. To test further the serotonergic hypothesis of
cerebellar ataxia, we administered
buspirone, a
5-HT1A agonist usable in human medicine, in a randomized double blind
drug placebo trial for 4 months. Nineteen patients with CCA were included; nine patients were given placebo and 10
Buspirone, at the mean dose of 0.69 mg/kg. The evaluation of
ataxia was based on a static and a kinetic
ataxia scale, fully quantitative measures and the evaluation of the sway path and area at posturography. At 4 months, a significant effect of
buspirone was observed for
drug induced gains of the kinetic score, two items of the static score, and the maximum duration of standing upright with feet together. These results indicate that a novel chemical therapeutic approach is possible for
cerebellar ataxia; moreover, they support the existence of a link between
cerebellar ataxia and disturbances of the serotonergic cerebellar system, especially a serotonergic deficit.