STN-DBS In Parkinson's Disease Patients Research Articles

Freezing of gait depends on cortico-subthalamic network recruitment following STN-DBS in PD patients

IntroductionSubthalamic deep-brain-stimulation (STN-DBS) is an effective means to treat Parkinson's disease (PD) symptoms. Its benefit on gait disorders is variable, with freezing of gait (FOG) worsening in about 30% of cases. Here, we investigate the clinical and anatomical features that could explain post-operative FOG. MethodsGait and balance disorders were assessed in 19 patients, before and after STN-DBS using clinical scales and gait recordings. The location of active stimulation contacts were evaluated individually and the volumes of activated tissue (VAT) modelled for each hemisphere. We used a whole brain tractography template constructed from another PD cohort to assess the connectivity of each VAT within the 39 Brodmann cortical areas (BA) to search for correlations between postoperative PD disability and cortico-subthalamic connectivity. ResultsSTN-DBS induced a 100% improvement to a 166% worsening in gait disorders, with a mean FOG decrease of 36%. We found two large cortical clusters for VAT connectivity: one “prefrontal”, mainly connected with BA 8,9,10,11 and 32, and one “sensorimotor”, mainly connected with BA 1-2-3,4 and 6. After surgery, FOG severity positively correlated with the right prefrontal VAT connectivity, and negatively with the right sensorimotor VAT connectivity. The right prefrontal VAT connectivity also tended to be positively correlated with the UPDRS-III score, and negatively with step length. The MDRS score positively correlated with the right sensorimotor VAT connectivity. ConclusionRecruiting right sensorimotor and avoiding right prefrontal cortico-subthalamic fibres with STN-DBS could explain reduced post-operative FOG, since gait is a complex locomotor program that necessitates accurate cognitive control.

Altered Interhemispheric Functional Connectivity Associated With Early Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease.

BackgroundPatients with Parkinson’s disease (PD) experience a decline in verbal fluency (VF) immediately after undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN). This phenomenon is thought to be related to surgical microlesions.PurposeWe investigated the alterations in interhemispheric functional connectivity after STN-DBS in PD patients. We also evaluated the correlation between these changes and decreased VF scores.MethodOverall, 30 patients with PD were enrolled in the study. Resting-state functional magnetic resonance imaging scans were performed twice, once before and once after DBS, in PD patients. Voxel-mirrored homotopic connectivity (VMHC) was applied in order to evaluate the synchronicity of functional connectivity between the hemispheres.ResultAfter undergoing STN-DBS, PD patients demonstrated reduced VMHC value in the posterior cerebellum lobe, angular gyrus, precuneus/posterior cingulate gyrus (PCC), supramarginal gyrus, superior frontal gyrus (SFG) (medial and dorsolateral) and middle frontal gyrus (MFG). In addition, we observed a significant positive correlation between the altered VMHC value in the SFG and MFG and the change of phonemic VF scores.ConclusionPD patients demonstrated an interhemispheric coordination disorder in the prefrontal cortex, cerebellum, supramarginal gyrus and DMN after undergoing STN-DBS. The positive correlation between reduced VMHC value in the SFG and MFG and the changes of VF scores provides a novel understanding with regard to the decline of VF after DBS.

Low frequency subthalamic stimulation and event-related potentials in Parkinson disease

BackgroundHigh frequency (130 Hz) subthalamic Deep-Brain-Stimulation (STN-DBS) optimally improves cardinal motor symptoms in Parkinson disease (PD). Low stimulation frequencies (60–80 Hz) improve axial symptoms in some patients and, according to preliminary evidences, may also have a beneficial effect on the cognitive component of motor planning. ObjectiveTo analyze the configuration of the P300 component of cortical event-related auditory potentials (ERPs), a reliable index of attentive cognitive functions, at different stimulation frequencies in STN-DBS in PD patients. Methods12 PD patients underwent ERPs recordings using a standard oddball auditory paradigm with STN-DBS at 60 Hz, 80 Hz, 130 Hz, and OFF-stimulation, applied in a randomized double-blind sequence. ERPs analysis considered the peak amplitude and latency of the P300 components at midline electrode positions (Fz, Cz, Pz). ResultsP300 latency over Cz and Pz electrodes significantly increased with STN-DBS at 130 Hz compared to OFF-stimulation. P300 latency was also significantly increased, though to a lesser degree, over Pz electrode with stimulation at 80 Hz. No significant P300 latency modifications were detected at 60 Hz stimulation compared to OFF-stimulation condition. P300 amplitude did not change significantly for any of the stimulation conditions tested. ConclusionsLow frequency STN-DBS is associated with minor modifications of P300 latency compared to conventional stimulation at 130 Hz, possibly suggesting that 60 and 80 Hz may have less interference with attentive and cognitive processes in PD patients.

Acute Effects of Subthalamic Deep Brain Stimulation on Motor Outcomes in Parkinson's Disease; 13 Year Follow Up.

Objective: Deep brain stimulation of the Subthalamic nucleus (STN-DBS) is a safe and well-established therapy for the management of refractory motor symptoms in Parkinson's disease (PD). Marked improvement in axial symptoms has been reported in the short term with STN-DBS but questions remain regarding the long-term efficacy of this intervention. We assessed the acute ON and OFF effects of STN-DBS in PD patients who have been treated with STN-DBS for over a decade.Methods: We assessed 11 patients with early-onset PD (9 men, 2 women; mean age, 57.1 ± 7.2 y; mean age at illness onset, 38.9 ± 7.5 y) managed with long-term bilateral STN-DBS (mean treatment duration, 13.4 ± 1.3 y). Motor symptoms were assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS)-III, Timed Up and Go test (TUG), and Hoehn-Yahr scale. Motor assessments in the medication ON and OFF states with stimulation ON and OFF conditions were documented and video recorded.Results: Patients showed a significant improvement in motor symptoms both in the off-medication and on-medication state by a 54% reduction (off-medication/on-stimulation vs. off-medication/off-stimulation) and a 48% reduction (on-medication/on-stimulation vs. on-medication/off-stimulation) in the total UPDRS-III score. Specifically, improvement in axial symptoms (off-medication: 51% reduction; on-medication: 44% reduction), including gait but not posture. Similarly, STN-DBS reduced TUG scores (off-medication: 70% reduction; on-medication: 47% reduction).Conclusions: On stimulation long-term, bilateral STN-DBS can improve appendicular and axial symptoms of patients with early-onset PD in the acute setting.

The Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease: Is There an Influence of Age?

DBS is commonly used to treat Parkinson's disease (PD). DBS is not considered to cause major cognitive side effects, but some research groups have reported that it can cause decreased verbal fluency. The influence of age on DBS cognitive outcome is unclear. We investigated the possible influence of patients' age, level of education, disease duration, disease progression, depression, and levodopa equivalent dose (LED) on verbal fluency performance in patients with PD who underwent DBS of the subthalamic nucleus (STN-DBS). In this article, we investigated the influence of demographic and clinical parameters, especially age, on cognitive performance post-DBS in PD patients. Forty-three patients with PD and without major psychiatric illness (according to Diagnostic and Statistical Manual of Mental Disroders, Fourth Edition) were enrolled in the study. Median age was 64.0 years (range, 46-77). In 21 patients, the indication for DBS was established on clinical grounds in keeping with international guidelines; these patients underwent STN-DBS, and the remaining 22 did not. Cognitive performance in both groups was assessed by standard neuropsychological test batteries at baseline and after median follow-up of 7 months. A statistically significant decline in the semantic category of verbal fluency task was found in the STN-DBS group (P < 0.01). Linear regression model revealed an influence of age (P < 0.01) and disease duration (P < 0.01) in relation to this decline. This study confirms previous findings that verbal fluency declines after STN-DBS in PD patients in comparison to PD patients without DBS. This decline is related to age and disease duration.

Personality changes after deep brain stimulation in Parkinson's disease.

Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson's disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P = 0.006; P = 0.024). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P = 0.027). Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity.

Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson’s disease

The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus mental aspects of QoL in PD remains unknown. To assess the influence of bilateral STN DBS on physical versus mental aspects of QoL in Parkinson's disease. The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS. Comparing off-dopa conditions before versus 12 months after surgery, both UPDRS part II and part III significantly improved: 32.6% and 52%, respectively. UPDRS part I scores did not change significantly at 12 months. As for PDQ39, the global score significantly improved after surgery (21.1 %) as did four subscores: mobility (25.6 %), activity of daily living (34.5 %), stigma (40.1 %) and bodily discomfort (30 %). Three PDQ39 subscores, however, showed no significant changes: emotional well-being (10.7 %), social support (3.2%) and cognition (8.5 %) and one item even worsened: communication (-7.7 %). In SF36, only physical items significantly improved. Using clinician's based rating scale, bilateral STN DBS showed significant improvement in PD patients at 12 month follow up. However, using patient's self-assessment scales, the clinical benefit of STN DBS was more subtle: physical items of QoL significantly improved, whereas mental items such as emotional well-being, social support, cognition and communication showed no improvement. Our results are suggestive of a dissociation of motor and non-motor symptoms control after bilateral STN DBS in PD patients.