New Targets for Deep Brain Stimulation Treatment of Parkinson's Disease

Anna Castrioto; Elena Moro


Expert Rev Neurother. 2013;13(12):1319-1328. 

In This Article

Alternative Targets for Non-motor Symptoms in PD

The bulk of the studies on DBS in PD has focused on motor symptoms. However, PD is not a mere motor disorder. Several non-motor symptoms develop at different stages of disease, and among them cognitive impairment is certainly one of the most disabling for patients and caregivers. Dementia affects almost 30% of PD patients and mild cognitive impairment around 15–20% of patients at early stages of disease.[75] In a longitudinal study at 20 years from the disease onset, around 80% of patients had developed dementia.[76]

Management of cognitive impairment at present is based on pharmacological and physical treatment and it is still unsatisfactory. Recently, in a patient undergoing hypothalamic stimulation for the treatment of morbid obesity it was serendipitously discovered that the stimulation of the fornix/hypothalamus could evoke detailed autobiographic memory events in a reproducible and consistent manner.[77] Following this unexpected observation, a Phase I trial of fornix/hypothalamic stimulation has been carried out in six patients with mild-moderate Alzheimer's disease. Preliminary results showed a reversal of the impaired glucose hypometabolism in the temporal and parietal cortex at PET scans and a slower than expected decline of the Mini-Mental State Examination score.[78] Larger randomized studies are needed to confirm this preliminary data. Nevertheless, taking also into consideration that the pattern of cognitive impairment in PD is quite different, the rationale of fornix stimulation in PD patients remains to be demonstrated.

Concerning sleep, a positive effect on sleep and daytime sleepiness has been reported with PPN stimulation (see above).[23,32,33,79]