Subthalamic and nigral stimulation for freezing of gait in Parkinson's disease: Randomized pilot trial

We aimed to identify novel therapeutic approaches for freezing of gait (FoG), a disabling symptom of Parkinson's disease (PD) associated with risk of falls and poor life quality. FoG affects 31 up to 87% of PD patients and can be difficult to manage with standard PD medications. FoG may remain unchanged or even worsen in patients treated with Deep Brain Stimulation (DBS). We focused on DBS-treated PD patients and stimulated simultaneously two areas of the brain: the subthalamic nucleus (STN), the typical target for treating PD motor symptoms, and the substantia nigra pars reticulata (SNr). 15 PD patients with FoG received different types of brain stimulation for one month each: STN stimulation alone and combined STN + SNr stimulation at two different stimulation frequencies. We measured improvement of FoG (using a validated questionnaire) and other PD symptoms (including motor fluctuations, anxiety and depression, and sleep quality), as well as safety and tolerability of the combined STN + SNr stimulation. Finally, we observed the patient preference for the type of stimulation provided. We found no statistically significant change of FoG scores with STN + SNr stimulation, but one-third of patients experienced a clinically meaningful reduction in FoG. STN + SNr stimulations helped improve motor fluctuations and dyskinesia. Moreover, 80% of the patients preferred the combined stimulation over the standard STN stimulation. We believe this data suggest that combined STN + SNr stimulation could be a valuable area for further research aiming to improve FoG and can be safely attempted in clinical practice in DBS-treated patients with disabling FoG.