SLEEP MODULATION IN PARKINSON'S DISEASE PATIENTS WITH DEEP BRAIN STIMULATION: THE ROLE OF FREQUENCY VARIATIONS

Introduction: Deep Brain Stimulation (DBS) is an effective treatment for motor symptom in Parkinson’s Disease(PD). Since sleep alterations are a frequent non-motor symptom in PD, DBS is shown to modify also sleep parameters. Low frequencies stimulation are used in Subthalamic Nucleus(STN) DBS in PD patients to improve gait disorders and the hypothesis of a possible involvement of these frequencies of the Peduncolo Pontine Nucleus (PPN) was advanced. PPN is a brainstem nucleus involved in locomotion but also in sleep modulation, especially in REM sleep. The aim of our study was to investigate the differences between low (60Hz) versus high (130hz ) frequencies of STN DBS in PD patients (PD-DBS) in sleep parameters. We also explored differences in sleep parameters between PD-DBS patients and PD patients with only medical treatment (PD-MED) and healthy controls (HC). Materials and Methods: PD-DBS and PD-MED non demented patients were recruited at the Movement Disorders Clinic of our Hospital. Also HC age-matched were recruited. All patients underwent a full night laboratory polysomnography, while PD-DBS performed two recordings in different non consecutive days: a night with 60Hz frequency of stimulation, one night with 130Hz frequency of stimulation. Sleep conventional macrostructure and microstructure analysis was performed. Motor symptoms were evaluated with validated scale and with a wrist Actigraphy. EEG quantitative variables and sleep slow oscillation (SSO) analysis were explored for PD-DBS patients. Results: In our study 10 PD-DBS patients, 10 PD-MED and 10 HC were enrolled. Two PD-DBS patients were subsequently excluded from the analysis due to the presence of artifacts in the recordings. No differences in age or disease duration were found among groups. PD-DBS patients presented increased REM sleep duration during 60Hz stimulation compared to 130Hz.Phasic EMG activity during REM sleep was not different in the two stimulation conditions. NREM sleep (macrostructure and microstructure) was not significantly modified in the two stimulation conditions. When 60Hz frequency was used, an increase in Theta activity in EEG quantitative analysis was found during both REM and NREM sleep. No significant differences were found in SSO between the two stimulation conditions. Tremor was significantly higher at 60Hz frequency of stimulation than 130Hz. When the three groups were compared: PD-MED presented a significant lower number of REM periods and a trend towards significant of lower REM percentage than HC; PD-DBS patients when stimulated with 60Hz showed REM percentage and number of REM periods higher than PD-MED and with values similar than HC. Considering sleep microstructure PD-MED presented a reduced Total CAP Rate % than HC and A3 index was reduced in PD-MED and in PD-DBS 130Hz (but not at 60Hz) compared to HC. Conclusions: Low frequencies stimulation of STN could modulate sleep in PD patients increasing REM sleep, suggesting a possible involvement of other brain structures as PPN, as proposed for motor improvement with these stimulation setting. STN stimulation at 60Hz seems to not cause major modification of NREM sleep and microstructure of sleep, while DBS shows globally a modulation effect on sleep improving sleep parameters compared to PD-MED patients.