Brain Stimulation Of Subthalamic Nucleus Research Articles

ON/OFF non-motor evaluation: a new way to evaluate non-motor fluctuations in Parkinson’s disease

BackgroundNMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity...

Variable frequency deep brain stimulation of subthalamic nucleus to improve freezing of gait in Parkinson's disease.

Variable frequency deep brain stimulation of subthalamic nucleus to improve freezing of gait in Parkinson's disease.

Mixed anxiety-depressive disorder in Parkinson's disease associated with worse resting state functional response to deep brain stimulation of subthalamic nucleus

BackgroundParkinson's disease (PD), even though generally perceived as a dominantly motor disorder, is associated with a wide range of non-motor symptoms, including mixed anxiety-depressive disorder (MADD). ObjectivesThe aim of the presented study was to determine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) brings the functional characteristics of non-motor networks closer to the condition detected in healthy population and whether pre-DBS presence of MADD in PD patients was associated with different reaction to this therapeutic modality. MethodsResting-state fMRI signature elicited by STN DBS activation and deactivation in 81 PD patients was compared against healthy controls, with the focus on measures of efficiency of information processing and localised subnetwork differences. ResultsWhile all the MRI metrics showed statistically significant differences between PD patients in DBS OFF condition and healthy controls, none were detected in such a comparison against DBS ON condition. Furthermore, in the post-DBS evaluation, PD patients with MADD in the pre-DBS stage showed no differences in depression scales compared to pre-DBS psychiatrically intact PD patients, but still exhibited lower DBS-related connectivity in a subnetwork encompassing anterior and posterior cingulate, dorsolateral prefrontal and medial temporal cortices. ConclusionsSTN DBS improved all the metrics of interest towards the healthy state, normalising the resting-state MRI signature of PD. Furthermore, pre-DBS presence of MADD, even though clinically silent at post-DBS MRI acquisition, was associated with lower DBS effect in areas highly relevant for depression. This finding points to a possibly latent nature of post-DBS MADD, calling for caution in further follow-up of these patients.

Deep brain stimulation of the subthalamic nucleus restores spatial reversal learning in patients with Parkinson's disease.

Spatial learning and navigation are supported by distinct memory systems in the human brain such as the hippocampus-based navigational system and the striatum-cortex-based system involved in motor sequence, habit and reversal learning. Here, we studied the role of subthalamic circuits in hippocampus-associated spatial memory and striatal-associated spatial reversal learning formation in patients with Parkinson's disease, who underwent a deep brain stimulation of the subthalamic nucleus. Deep brain stimulation patients (Parkinson's disease-subthalamic nucleus: n = 26) and healthy subjects (n = 15) were tested in a novel experimental spatial memory task based on the Morris water maze that assesses both hippocampal place memory as well as spatial reversal learning. All subjects were trained to navigate to a distinct spatial location hidden within the virtual environment during 16 learning trials in a subthalamic nucleus Stim-On condition. Patients were then randomized into two groups with either a deep brain stimulation On or Off condition. Four hours later, subjects were retested in a delayed recall and reversal learning condition. The reversal learning was realized with a new hidden location that should be memorized during six consecutive trials. The performance was measured by means of an index indicating the improvement during the reversal learning. In the delayed recall condition, neither patients, healthy subjects nor the deep brain stimulation On- versus Off groups showed a difference in place memory performance of the former trained location. In the reversal learning condition, healthy subjects (reversal index 2.0) and patients in the deep brain stimulation On condition (reversal index 1.6) showed a significant improvement. However, patients in the deep brain stimulation Off condition (reversal index 1.1) performed significantly worse and did not improve. There were no differences between all groups in a final visual guided navigation task with a visible target. These results suggest that deep brain stimulation of subthalamic nucleus restores spatial reversal learning in a virtual navigation task in patients with Parkinson's disease and gives insight into the neuromodulation effects on cognition of subthalamic circuits in Parkinson's disease.

Structural and microstructural predictors of cognitive decline in deep brain stimulation of subthalamic nucleus in Parkinson’s disease

Background and objectivesThe intricate relationship between deep brain stimulation (DBS) in Parkinson’s disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. MethodsPre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population – Dementia Rating Scale 2. ResultsPD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. ConclusionsOur findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.

One-pass deep brain stimulation of subthalamic nucleus and ventral intermediate nucleus for levodopa-resistant tremor-dominant Parkinson's disease.

Tremor-dominant Parkinson's disease (TD-PD) can be further separated into levodopa-responsive and levodopa-resistant types, the latter being considered to have a different pathogenesis. Previous studies indicated that deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the globus pallidus internus (GPi) individually was not sufficient for tremor control, especially for the levodopa-resistant TD-PD (LRTD-PD). The thalamic ventral intermediate nucleus (VIM) has been regarded as a potent DBS target for different kinds of tremors. Therefore, we focused on the LRTD-PD subgroup and performed one-pass combined DBSs of STN and VIM to treat refractory tremors, aiming to investigate the safety and effectiveness of this one-trajectory dual-target DBS scheme. We retrospectively collected five LRTD-PD patients who underwent a one-pass combined DBS of STN and VIM via a trans-frontal approach. The targeting of VIM was achieved by probabilistic tractography. Changes in severity of symptoms (measured by the Unified Parkinson Disease Rating Scale part III, UPDRS-III), levodopa equivalent daily doses (LEDD), and disease-specific quality of life (measured by the 39-item Parkinson's Disease Questionnaire, PDQ-39) were evaluated. Three-dimensional reconstruction of electrodes illustrated that all leads were successfully implanted into predefined positions. The mean improvement rates (%) were 53 ± 6.2 (UPDRS-III), 82.6 ± 11.4 (tremor-related items of UPDRS), and 52.1 ± 11.4 (PDQ-39), respectively, with a mean follow-up of 11.4 months. One-pass combined DBS of STN and VIM via the trans-frontal approach is an effective and safe strategy to alleviate symptoms for LRTD-PD patients.

Mechanisms and consequences of weight gain after deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Body weight gain in combination with metabolic alterations has been observed after deep brain stimulation (DBS) of subthalamic nucleus (STN) in patients with Parkinson’s disease (PD), which potentially counteracts the positive effects of motor improvement. We aimed to identify stimulation-dependent effects on motor activities, body weight, body composition, energy metabolism, and metabolic blood parameters and to determine if these alterations are associated with the local impact of DBS on different STN parcellations. We assessed 14 PD patients who underwent STN DBS (PD-DBS) before as well as 6- and 12-months post-surgery. For control purposes, 18 PD patients under best medical treatment (PD-CON) and 25 healthy controls (H-CON) were also enrolled. Wrist actigraphy, body composition, hormones, and energy expenditure measurements were applied. Electrode placement in the STN was localized, and the local impact of STN DBS was estimated. We found that STN DBS improved motor function by ~ 40% (DBS ON, Med ON). Weight and fat mass increased by ~ 3 kg and ~ 3% in PD-DBS (all P ≤ 0.005). fT3 (P = 0.001) and insulin levels (P = 0.048) increased solely in PD-DBS, whereas growth hormone levels (P = 0.001), daily physical activity, and VO2 during walking were decreased in PD-DBS (all P ≤ 0.002). DBS of the limbic part of the STN was associated with changes in weight and body composition, sedentary activity, insulin levels (all P ≤ 0.040; all r ≥ 0.56), and inversely related to HOMA-IR (P = 0.033; r = − 0.62). Daily physical activity is decreased after STN DBS, which can contribute to weight gain and an unfavorable metabolic profile. We recommend actigraphy devices to provide feedback on daily activities to achieve pre-defined activity goals.

Muscle synergies in Parkinson’s disease before and after the deep brain stimulation of the bilateral subthalamic nucleus

The aim of this study is to quantitatively assess motor control changes in Parkinson’s disease (PD) patients after bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS), based on a novel muscle synergy evaluation approach. A group of 20 PD patients evaluated at baseline (before surgery, T0), at 3 months (T1), and at 12 months (T2) after STN-DBS surgery, as well as a group of 20 age-matched healthy control subjects, underwent an instrumented gait analysis, including surface electromyography recordings from 12 muscles. A smaller number of muscle synergies was found in PD patients (4 muscle synergies, at each time point) compared to control subjects (5 muscle synergies). The neuromuscular robustness of PD patients—that at T0 was smaller with respect to controls (PD T0: 69.3 ± 2.2% vs. Controls: 77.6 ± 1.8%, p = 0.004)—increased at T1 (75.8 ± 1.8%), becoming not different from that of controls at T2 (77.5 ± 1.9%). The muscle synergies analysis may offer clinicians new knowledge on the neuromuscular structure underlying PD motor types of behavior and how they can improve after electroceutical STN-DBS therapy.

Deep Brain Stimulation of Subthalamic Nucleus Improves Quality of Life in General and Mental Health Domains in Parkinson’s Disease to the Level of the General Population

ObjectivesParkinson’s disease (PD) leads to significant impairment in quality of life (QoL) across various domains. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is known to improve motor and nonmotor symptoms in PD. The aim was to study whether STN-DBS could improve the QoL of patients with PD to the level of the general population, and to determine factors predicting better motor outcomes. Materials and MethodsThe retrospective analysis included 43 patients who underwent either primary or revision STN-DBS. Patients filled out a general QoL questionnaire (RAND 36-item health survey) before and 12 months after surgery, and scores were compared with age- and sex-adjusted national population values. In addition, motor scores were calculated using Unified Parkinson Disease Rating Scale part 3 (UPDRS 3) with the best PD medication. Levodopa equivalent daily dose (LEDD) was also collected. Changes in the QoL were compared with operation age, disease duration, and preoperative QoL. ResultsPreoperatively, patients had significantly impaired QoL in all subsections compared with that of the general population. The mean postoperative UPDRS 3 improvement was 50.0%, and reduction in LEDD was 69.0%. Statistically significant QoL improvements were found in Physical Function, Mental Health, Social Function, Vitality, and Role Physical 12 months postoperatively compared with baseline. The mean differences compared with a healthy population were not statistically significant in General Health, Mental Health, Vitality, and Role Emotional. Furthermore, disease duration was found to be negatively correlated with improvements in UPDRS 3 score, and worse preoperative QoL positively correlated with changes in Physical Function. ConclusionsPatients experienced significant QoL improvements after STN-DBS. The General Health and Mental Health of patients were postoperatively most comparable with age- and sex-adjusted population values. Moreover, earlier stimulation predicted better motor improvements, which emphasizes the importance of earlier timing of STN-DBS surgery and minimizing loss of function at a critical disease stage.

Characteristics of Electroencephalogram in the Prefrontal Cortex during Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease under Propofol General Anesthesia.

Monitoring the depth of anesthesia by electroencephalogram (EEG) based on the prefrontal cortex is an important means to achieve accurate regulation of anesthesia for subthalamic nucleus (STN) deep brain stimulation (DBS) under general anesthesia in patients with Parkinson's disease (PD). However, no previous study has conducted an in-depth investigation into this monitoring data. Here, we aimed to analyze the characteristics of prefrontal cortex EEG during DBS with propofol general anesthesia in patients with PD and determine the reference range of parameters derived from the depth of anesthesia monitoring. Additionally, we attempted to explore whether the use of benzodiazepines in the 3 days during hospitalization before surgery impacted the interpretation of the EEG parameters. We included the data of 43 patients with PD who received STN DBS treatment and SedLine monitoring during the entire course of general anesthesia with propofol in a single center. Eighteen patients (41.86%) took benzodiazepines during hospitalization. We divided the anesthesia process into three stages: awake state before anesthesia, propofol anesthesia state, and shallow anesthesia state during microelectrode recording (MER). We analyzed the power spectral density (PSD) and derived parameters of the patients' prefrontal EEG, including the patient state index (PSI), spectral edge frequency (SEF) of the left and right sides, and the suppression ratio. The baseline characteristics, preoperative medication, preoperative frontal lobe image characteristics, preoperative motor and non-motor evaluation, intraoperative vital signs, internal environment and anesthetic information, and postoperative complications are listed. We also compared the groups according to whether they took benzodiazepines before surgery during hospitalization. The average PSI of the awake state, propofol anesthesia state, and MER state were 89.86 ± 6.89, 48.68 ± 12.65, and 62.46 ± 13.08, respectively. The preoperative administration of benzodiazepines did not significantly affect the PSI or SEF, but did reduce the total time of suppression, maximum suppression ratio, and the PSD of beta and gamma during MER. Regarding the occurrence of postoperative delirium and mini-mental state examination (MMSE) scores, there was no significant difference between the two groups (chi-square test, p = 0.48; Mann-Whitney U test, p = 0.30). For the first time, we demonstrate the reference range of the derived parameters of the depth of anesthesia monitoring and the characteristics of the prefrontal EEG of patients with PD in the awake state, propofol anesthesia state, and shallow anesthesia during MER. Taking benzodiazepines in the 3 days during hospitalization before surgery reduces suppression and the PSD of beta and gamma during MER, but does not significantly affect the observation of anesthesiologists on the depth of anesthesia, nor affect the postoperative delirium and MMSE scores.

Nomogram for Prediction of Postoperative Delirium after Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease under General Anesthesia.

Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson's disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson's disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium. A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56-13.02, p < 0.01) was the most important risk factor; other independent predictors were orthostatic hypotension (OR 3.42, 95% CI 0.90-13.06, p=0.07), inhibitors of type-B monoamine oxidase (OR 3.07, 95% CI 1.17-8.04, p=0.02), preoperative MRI with silent brain ischemia or infarction (OR 2.36, 95% CI 0.90-6.14, p=0.08), Hamilton anxiety scale score (OR 2.12, 95% CI 1.28-3.50, p < 0.01), and apolipoprotein E level in plasma (OR 1.48, 95% CI 0.95-2.29, p=0.08). The area under the receiver operating characteristic curve (AUC) was 0.76 (95% CI 0.66-0.86). A nomogram was established and showed good calibration and clinical predictive capacity. After bootstrap for internal verification, the AUC was 0.74 (95% CI 0.66-0.83). This study provides evidence for the independent inducing factors of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. By predicting the development of delirium, our model may identify high-risk groups that can benefit from early or preventive intervention.

Risk Factors for Hiccups after Deep Brain Stimulation of Subthalamic Nucleus for Parkinson's Disease.

After deep brain stimulation (DBS), hiccups as a complication may lead to extreme fatigue, sleep deprivation, or affected prognosis. Currently, the causes and risk factors of postoperative hiccups are unclear. In this study, we investigated the risk factors for hiccups after DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD) under general anesthesia. We retrospectively included patients who underwent STN DBS in the study, and collected data of demographic characteristics, clinical evaluations, and medications. According to the occurrence of hiccups within seven days after operation, the patients were divided into a hiccups group and non-hiccups group. The potentially involved risk factors for postoperative hiccups were statistically analyzed by logistic regression analysis. A total of 191 patients were included in the study, of which 34 (17.80%) had postoperative transient persistent hiccups. Binary univariate logistic regression analysis showed that male, higher body mass index (BMI), smoker, Hoehn and Yahr stage (off), preoperative use of amantadine, hypnotic, Hamilton anxiety scale and Hamilton depression scale scores, and postoperative limited noninfectious peri-electrode edema in deep white matter were suspected risk factors for postoperative hiccups (p &lt; 0.1). In binary multivariate logistic regression analysis, male (compared to female, OR 14.00; 95% CI, 1.74-112.43), postoperative limited noninfectious peri-electrode edema in deep white matter (OR, 7.63; 95% CI, 1.37-42.37), preoperative use of amantadine (OR, 3.64; 95% CI, 1.08-12.28), and higher BMI (OR, 3.50; 95% CI, 1.46-8.36) were independent risk factors for postoperative hiccups. This study is the first report about the risk factors of hiccups after STN DBS under general anesthesia for PD patients. The study suggests that male, higher BMI, preoperative use of amantadine, and postoperative limited noninfectious peri-electrode edema in deep white matter are independent risk factors for postoperative hiccups of STN-DBS for PD patients. Most hiccups after STN-DBS for PD patients were transient and self-limiting.

Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus Internus in Parkinson's Disease: A Meta-Analysis.

Parkinson's disease (PD) is a progressive neurodegenerative disorder typically manifested by its motor symptoms. In addition, PD patients also suffer from many nonmotor symptoms (NMSs), such as apathy. Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the globus pallidus internus (GPi) are recommended as therapeutic interventions for PD, given their pronounced benefit in reducing troublesome dyskinesia. Apathy, a mood disorder recognized as a NMS of PD, has a negative impact on the prognosis of PD patients. However, the effect of STN-DBS and GPi-DBS on apathy is controversial. In the current meta-analysis, we analyzed apathy following bilateral STN-DBS and GPi-DBS in PD patients. Relevant literature was retrieved from public databases, including PubMed, Cochrane Library, and Embase. Studies were included in our analysis based on the following criterion: such studies should report apathy scores presurgery and postsurgery determined by using the Starkstein Apathy Scale or Apathy Evaluation Scale in patients receiving STN or GPi-DBS with at least three months of follow-up. Upon applying this strict criterion, a total of 13 out of 302 studies were included in our study. A mean difference (MD) and 95% confidence interval (CI) were calculated to show the change in apathy scores. We found a statistically significant difference between the presurgery and postsurgery scores in patients receiving STN-DBS (MD = 2.59, 95% CI = 2.23–2.96, P < 0.00001), but not in patients receiving GPi-DBS (MD = 0.32, 95% CI = −2.78–3.41, P=0.84). STN-DBS may worsen the condition of apathy, which may result from the reduction of dopaminergic medication. In conclusion, STN-DBS seems to relatively worsen the condition of apathy compared to GPi-DBS. Further studies should focus on the mechanisms of postoperatively apathy and the degree of apathy in STN-DBS versus GPi-DBS.

Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait.

Freezing of gait is a debilitating symptom in advanced Parkinson’s disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson’s disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy for freezing of gait.Here, we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson’s disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials and quantified 7073 s of stable walking and 3384 s of gait freezing in conditions of on/off-stimulation and with/without dual-tasking.We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e. walking trials that contained freezing), but not non-freezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) non-freezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials.These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel ‘bandwidth model,’ which specifies the role of cortical dysfunction, cognitive burden and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.

P 44 Restitution of oral transport, penetration, and aspiration with nigral stimulation in Parkinson's disease?

Introduction: Dysphagia is common in advanced Parkinson's disease (PD) leading to aspiration and pneumonia. These complications are relevant for quality of life of patients and increase morbidity and mortality. Standard treatment such as dopaminergic medication and deep brain stimulation of subthalamic nucleus (STN) often fall short to improve dysphagia. Stimulation of the substantia nigra pars reticulata (SNr) is of interest in dysphagia since experimental models suggested that SNr might be involved to swallowing. Here, we hypothesized that the combined stimulation of STN and SNr improves dysphagia compared with standard subthalamic nucleus stimulation at eight weeks of treatment. Patients and Methods: We enrolled PD patients with dysphagia. After a screening visit, the eligible patients entered an eight-week active treatment phase. Patients were assessed in “medication on” and “standard STN” at baseline (V1) and then were randomized 1:1 “standard STN” or “STN+SNr”. During the 8-week follow-up the participants received swallowing therapy as a standard care therapy in addition. After eight-weeks we evaluated swallowing function and clinical measures in a follow-up visit (V2). We focused on the oral and pharyngeal phase of swallowing. Our primary endpoint was the Penetration-Aspiration Scale (PAS). Additional to PAS, a visual analog scale (VAS) for pharyngeal residue in vallecular space and sinus piriformes and Site of Swallow Reflex Initiation (SOS) provided us further information about pharyngeal phase, penetration, and aspiration. We chose the “Test of Mastication and Swallowing Solids” (TOMASS) to study oral preparation and transport, SWAL-QoL scale for dysphagia-associated quality of life, and Functional oral intake scale (FOIS) for functional dimension. Results: We enrolled 20 patients. The PAS showed no significant difference in change from baseline between groups (P = 0.221). As secondary finding, we found that both patients from the STN and STN+SNr group showed better PAS at V2 compared to V1. VAS score for pharyngeal residue in sinus piriformes for solid food showed better outcome in “standard STN” group compared to “STN+SNr” group compared with baseline as well (P= 0.011). A difference of the number of swallows in the TOMASS score was found with lower number of swallows in the STN group (P = 0.025). Other outcome measures showed no difference between the groups. Conclusion: Our study did not show a superior effect of STN+SNr compared to STN. However, we found that the patients globally improved with dysphagia irrespective from the stimulation condition. This probably reflected the effect of continuous swallowing therapy and the increased patients‘ awareness towards swallowing. A closer pathophysiological understanding of the neuronal circuitry is therefore needed for specific neuromodulation intervention.

P 37. The cognitive course in Parkinson's disease patients treated with Deep Brain Stimulation of subthalamic nucleus – Correlations with qEEG

Objective. Deep brain stimulation of the subthalamic nucleus (STN-DBS) improve motor functioning in Parkinson“s disease patients– Additionally it can also influence cognitive functioning. In most patients, a decline of verbal fluency test performance after STN-DBS is often reported. The purpose of this study was to determine whether preoperative quantitative electroencephalography (qEEG) may be useful in the preoperative assessment predicting cognitive changes in PD patients treated with STN-DBS. Methods. We compared the cognitive performance of 16 PD patients who underwent bilateral STN-DBS and 15 PD controls (matched for age, sex and education) at baseline as well as after 24 months. Cognitive scores were calculated for all patients across 5 cognitive domains covered by different cognitive tests (attention, executive function, episodic & working memory, verbal fluency, visuo-construction). A preoperative 256-channels EEG was recorded of each patient at rest and global relative power spectra were computed. Correlation and linear regression models were used to assess the association of preoperative EEG measures with postoperative cognitive scores in stimulated PD patients compared to PD controls. Results. The decline of verbal fluency performance after two years in the PD group treated with STN-DBS was significant in comparison to the PD controls ( p < 0.001). All other cognitive domains declined in the same manner as in the PD controls or remained stable over the 24-months period. EEG frequency analyses revealed increased global theta power (4-8 Hz) at baseline to be associated with reduced postoperative verbal fluency performance ( r = 0.50, p < 0.05) at follow-up. Conclusion. Consistent with the results of former studies, STN stimulation deteriorates verbal fluency in the course of two years. Accordingly, we observed significant decline in tests measuring verbal fluency in the group of PD patients treated with STN-DBS compared to a control group of PD patients. The decline of verbal fluency performance could be predicted by a reduced theta power at baseline. No other significant differences in cognitive alterations between patients in the STN-DBS group and the PD control group occur over two years.

Evaluation of the Direct Effect of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus on Levodopa-Induced On-Dyskinesia in Parkinson's Disease.

Objective: This study aimed to evaluate the direct anti-dyskinesia effect of deep brain stimulation (DBS) of subthalamic nucleus (STN) on levodopa-induced on-dyskinesia in Parkinson's disease (PD) patients during the early period after surgery without reducing the levodopa dosage.Methods: We retrospectively reviewed PD patients who underwent STN-DBS from January 2017 to October 2019 and enrolled patients with levodopa-induced on-dyskinesia before surgery and without a history of thalamotomy or pallidotomy. The Unified Dyskinesia Rating Scale (UDysRS) parts I+III+IV and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) were monitored prior to surgery, and at the 3-month follow-up, the location of active contacts was calculated by postoperative CT–MRI image fusion to identify stimulation sites with good anti-dyskinesia effect.Results: There were 41 patients enrolled. The postoperative levodopa equivalent daily dose (LEDD) (823.1 ± 201.5 mg/day) was not significantly changed from baseline (844.6 ± 266.1 mg/day, P = 0.348), while the UDysRS on-dyskinesia subscores significantly decreased from 24 (10–58) to 0 (0–18) [median (range)] after STN stimulation (P < 0.0001). The levodopa-induced on-dyskinesia recurred in stimulation-off/medication-on state in all the 41 patients and disappeared in 39 patients when DBS stimulation was switched on at 3 months of follow-up. The active contacts which correspond to good effect for dyskinesia were located above the STN, and the mean coordinate was 13.05 ± 1.24 mm lateral, −0.13 ± 1.16 mm posterior, and 0.72 ± 0.78 mm superior to the midcommissural point.Conclusions: High-frequency electrical stimulation of the area above the STN can directly suppress levodopa-induced on-dyskinesia.

Advanced Therapies for the Management of Dopamine Dysregulation Syndrome in Parkinson's Disease

Dopamine Dysregulation Syndrome (DDS) is an adverse non-motor complication of dopamine replacement therapy in Parkinson's disease. The current literature on this syndrome is limited, and it remains underdiagnosed and challenging to manage. To assess the role of advanced therapies in the management of DDS. We performed a retrospective chart review and identified patients who fit the inclusion criteria for DDS. They were classified according to risk factors that have been identified in the literature, motor and complication scores, intervention (medical or surgical) and outcome. Multivariate analyses were performed to analyze these characteristics. Twenty-seven patients were identified (23 males, mean age of onset: 49 ± 8.8 years). Average levodopa equivalent daily dose was 1916.7 ± 804 mg and a history of impulse control disorders, psychiatric illness, and substance abuse was present in 89%, 70% and 3.7% of the patients, respectively. Overall 81.5% of patients had symptom resolution at follow up, on average 4.8 ± 3.5 years after management, with medication only (7/9), levodopa-carbidopa intestinal gel (1/3), deep brain stimulation of subthalamic nucleus (10/13), or globus pallidus pars interna (2/2). Reduction of medications occurred with deep brain stimulation of subthalamic nucleus (P = 0.01) but was associated with a relapse in two patients. Although the small sample size of some subgroups limits our ability to draw meaningful conclusions, our results did not suggest superiority of a single treatment option. Advanced therapies including deep brain stimulation can be considered in patients with DDS refractory to conservative measures, but outcome is variable and relapse is possible.

Predicting Neurocognitive Change after Bilateral Deep Brain Stimulation of Subthalamic Nucleus for Parkinson's Disease

Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) is a standard surgical treatment option in patients with advanced Parkinson's disease. Adverse effects on cognitive function have been reported, impacting the quality of life of patients and caregivers. We aimed to investigate a quantitative predictive preexisting cognitive factor for predicting postoperative cognitive changes. Thirty-five patients underwent STN-DBS. A battery of neuropsychological tests were used to examine executive function, processing speed, and visuospatial function both preoperatively and 1 year postoperatively. A multiple logistic regression analysis was performed to investigate the relationships between preoperative factors and cognitive outcomes. The predictive value of the preoperative factors for global cognitive decline during long-term follow-up were evaluated. The patients exhibited significant changes in processing speed and visuospatial function after surgery. Using reliable change index values, lower preoperative scores on the Similarities and Object Assembly subtests of the Wechsler Adult Intelligence Scale III were associated with decreases in visuospatial function at 1 year after DBS. The odds ratios were 10.2 for Similarities and 9.53 for Object Assembly. The proportion of Mini Mental State Examination-maintained patients with low scores on the Similarities subtest was significantly lower than that of patients with high scores at 3 and 5 years. No factors were found to be related to decreases in processing speed. Preoperative evaluation of the Similarities and Object Assembly subtests may be useful to identify patients who are at a greater risk of experiencing decreases in visuospatial functioning after STN-DBS. Furthermore, a low score on the Similarities subtest may predict future global cognitive deterioration.

The effect on deep brain stimulation of subthalamic nucleus and dopaminergic treatment in Parkinson disease.

Impulsivity is a frequent non-motor symptom in Parkinson disease (PD). It comprises psycho-behavioral alterations that negatively impact quality of life. Dopaminergic treatments underpin many impulsive controls disorders however, side effects, such as increased impulsivity, are described also after neurosurgical procedure of deep brain stimulation (DBS). We investigated the effect of deep brain stimulation on psycho-behavioral alterations and quality of life (QoL) in PD patients, analyzing, also, the role of dopaminergic therapies.Twenty idiopathic PD patients with and 20 idiopathic PD patients without DBS were included in the study. All patient underwent to neuropsychological assessment for a screening of executive functions, impulsivity, anxiety and depressive symptoms and QoL.Differences were found between DBS and no DBS groups and in term of dopaminergic therapies. The comparison between 2 groups showed a greater motor and attentional impulsivity in DBS patients. Moreover, this impulsivity worse QoL and interpersonal relationships. The combination of Levodopa and dopamine agonists exerted a great impact on impulsivity behavior.The emergence of postoperative impulsivity seems to be a neurostimulator phenomenon related to the computational role of the subthalamic nucleus in modulation of behavior.