Functional Role of the Cerebellum in Parkinson Disease: A PET Study.

OBJECTIVES: To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism. METHODS: We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations. RESULTS: Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters. CONCLUSIONS: These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.

Subthalamic nucleus stimulation affects fear and sadness recognition in Parkinson's disease.

Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) can produce emotional disorders that have been linked to disturbance of the STN's limbic territory. The aim of this study was to confirm the impairment of the recognition of facial emotions (RFE) induced by STN DBS, not only ruling out the effect of the disease's natural progression in relation to the effect of DBS, but also assessing the influence of modifications in dopamine replacement therapy (DRT) following STN DBS. RFE was investigated in 24 PD patients who underwent STN DBS and 20 PD patients treated with apomorphine. They were assessed 3 months before and after treatment. The 2 patient groups were compared with a group of 30 healthy matched controls. The results showed that RFE for negative emotions (fear and sadness) was impaired in only the STN DBS group in the posttreatment condition and was unrelated to DRT. Results confirm the selective reduction of RFE induced by STN DBS, due neither to the disease's natural progression nor to modifications in DRT.

Subthalamic nucleus stimulation in severe obsessive-compulsive disorder.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.)

Fear recognition is impaired by subthalamic nucleus stimulation in Parkinson's disease.

Behavioural disturbances such as disorders of mood, apathy or indifference are often observed in Parkinson's disease (PD) patients with chronic high frequency deep brain stimulation of subthalamic nucleus (STN DBS). Neuropsychological modifications causing these adverse events induced by STN DBS remain unknown, even if limbic disturbances are hypothesised. The limbic system supports neural circuits processing emotional information. The aim of this work is to evaluate changes of emotional recognition in PD patients induced by STN DBS. Thirty PD patients were assessed using a computerised paradigm of recognition of emotional facial expressions [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto, CA: Consulting Psychologists Press], 15 before STN DBS and 15 after. The two patients groups were compared to a group of 15 healthy control subjects. One series of 55 pictures of emotional facial expressions was presented to each patient. Patients had to classify the pictures according to seven basic emotions (happiness, sadness, fear, surprise, disgust, anger and no emotion). The intact ability to percept faces was firstly assured using the Benton Recognition Test. Recognition of fear expressions was significantly and selectively reduced in the post-operative group in comparison to both pre-operative and control groups. Our results demonstrate for the first time a selective reduction of recognition of facial expressions of fear by STN DBS. This impairment could be the first neuropsychological marker of a more general limbic dysfunction, thought to be responsible for the behavioural disorders reported after STN DBS.

Staged lesions through implanted deep brain stimulating electrodes: a new surgical procedure for treating tremor or dyskinesias.

Thalamotomy and pallidotomy have been shown to have some efficacy for treating some movement disorders such as disabling tremor or parkinsonian levodopa-induced dyskinesias (LID). Compared to continuous deep brain stimulation (DBS), this surgical procedure has the disadvantage of irreversibility and a lack of adaptability. Making a lesion involves a risk of inducing permanent side effects, especially if the lesion is large, or of observing a resurgence of the symptoms if the lesion is too small. We performed unilateral pallidotomy in one patient suffering from LID and unilateral thalamotomy in two patients suffering from tremor through the lead classically used for DBS. The technique of lead implantation was similar to that used for DBS treatment but, instead of connecting the lead to a pulse generator, it was left in place and used to make a radiofrequency lesion. This technique allowed the lesion to be kept as small as possible, thereby minimizing the risk of permanent side effects and made possible to extend the lesion if the symptoms reappeared. One lesioning session was enough to relieve tremor in the two patients treated by thalamotomy; three lesioning sessions over a 7-month period were required to relieve drug-induced dyskinesias in the patient treated by pallidotomy. In all 3 patients, disabling symptoms were still relieved without any permanent side effects 6 months after the last lesion was performed.