Tetrabenazine and subthalamic stimulation in graft-induced dyskinesias

Putaminal fetal ventral mesencephalic stem cell transplantation has been advocated as a sustainable treatment for Parkinson disease (PD). Double-blind randomized clinical trials have inconclusively proven their benefit in the motor symptoms of PD despite evidence of graft viability, as shown by [18F]-fluorodopa PET.1 At variable intervals after grafting, 15%–57% of patients develop graft-induced dyskinesias (GID), which are characterized by violent, choreo-ballistic dyskinesias occurring regardless of the patient's medication state.2 GID are particularly difficult to manage: they do not respond to withdrawal of antiparkinsonian medication and deep brain stimulation (DBS) of the pars interna of the globus pallidus produces variable results.3 The etiopathogenesis of GIDs is debated and implicates both excessive dopaminergic neural transmission and nondopaminergic mechanisms. As for the latter, animal models and imaging studies on grafted patients have hypothesized that grafted tissues comprise a heterogeneous population of neurons, including serotoninergic ones, which in turn may contribute to GID.4 This notion led to the 5HT1A agonist buspirone to be trialed, successfully, to acutely reduce GID.2,4 Chronic treatment with buspirone has not improved all patients experiencing GID.5
Source: Neurology - Category: Neurology Authors: Tags: CLINICAL/SCIENTIFIC NOTES Source Type: research