Severe, refractory obsessive–compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option. In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests. After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [±SD], 19±8 vs. 28±7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56±14 vs. 43±8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events. These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)

Objective: To prospectively evaluate the impact of subthalamic nucleus (STN) stimulation on social adjustment in patients with Parkinson disease (PD).

To analyse 24 parkinsonian patients successfully treated by bilateral STN stimulation for the presence of behavioural disorders. patients were evaluated retrospectively for adjustment disorders (social adjustment scale, SAS), psychiatric disorders (comparison of the results of psychiatric interview and the mini international neuropsychiatric inventory) and personality changes (IOWA scale of personality changes). parkinsonian motor disability was improved by 69.5% and the levodopa equivalent daily dosage was reduced by 60.5%. Social adjustment (SAS) was considered good or excellent in nine patients, moderately (n=14), or severely (n=1) impaired in 15 patients. Psychiatric disorders consisted of amplification or decompensation of previously existing disorders that had sometimes passed unnoticed, such as depressive episodes (n=4), generalised anxiety (n=18), and behavioural disorders with drug dependence (n=2). Appearance of mild to moderate emotional hyperreactivity was reported in 15 patients. Personality traits (IOWA scale) were improved in eight patients, unchanged in seven, and aggravated in eight Improvement in parkinsonian motor disability induced by STN stimulation is not necessarily accompanied by improvement in psychic function and quality of life. Attention is drawn to the possible appearance of personality disorders and decompensation of previous psychiatric disorders in parkinsonian patients who are suitable candidates for neurosurgery. We suggest that a careful psychological and psychiatric interview be performed before surgery, and emphasise the need for psychological follow up to ensure the best possible outcome.

Two parkinsonian patients who experienced transient hypomanic states when the subthalamic nucleus (STN) was stimulated during postoperative adjustment of the electrical parameters for antiparkinsonian therapy agreed to have the mood disorder reproduced, in conjunction with motor, cognitive, and behavioral evaluations and concomitant functional neuroimaging. During the experiment, STN stimulation again induced a hypomanic state concomitant with activation of cortical and thalamic regions known to process limbic and associative information. This observation suggests that the STN plays a role in the control of a complex behavior that includes emotional as well as cognitive and motor components. The localization of the four contacts of the quadripolar electrode was determined precisely with an interactive brain atlas. The results showed that (i) the hypomanic state was caused only by stimulation through one contact localized in the anteromedial STN; (ii) both this contact and the contact immediately dorsal to it improved the parkinsonian motor state; (iii) the most dorsal and ventral contacts, located at the boundaries of the STN, neither induced the behavioral disorder nor improved motor performance. Detailed analysis of these data led us to consider a model in which the three functional modalities, emotional, cognitive, and motor, are not processed in a segregated manner but can be subtly combined in the small volume of the STN. This nucleus would thus serve as a nexus that integrates the motor, cognitive, and emotional components of behavior and might consequently be an effective target for the treatment of behavioral disorders that combine emotional, cognitive, and motor impairment.

Background: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson’s disease (PD) are well documented, but long term benefits are still uncertain. Objectives: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. Methods: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). Results: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% (“off” drug) and 60% (“on” drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% (“off” drug) and 73% (“on” drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. Conclusions: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.