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Purpose: This systematic review focuses on the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on language function in Parkinson's disease (PD). It fills an important gap in recent reviews by considering other language tasks in addition to verbal fluency. Method: We critically and systematically reviewed the literature on studies that investigated the effect of bilateral STN-DBS on language function in PD. All studies included a matched PD control group who were on best medical treatment, with language testing at similar baseline and follow-up intervals as the DBS PD group. Results: Thirteen identified studies included a form of a verbal fluency task, seven studies included picture naming, and only two studies included more language-oriented tasks. We found that verbal fluency was negatively affected after DBS, whereas picture naming was unaffected. Studies investigating individual change patterns using reliable change indices showed that individual variability is larger for picture naming than for verbal fluency. Conclusions: Verbal fluency is the most frequently investigated aspect of language function. Our analysis showed a pattern of decline in verbal fluency across multiple studies after STN-DBS, whereas picture naming was unaffected. Data on more language-oriented tests in a large DBS sample and best medical treatment control group are sparse. The investigation of language function in PD after DBS requires sensitive language tests (with and without time pressure) and experimental designs as used in the studies reviewed here. Reliable change index statistics are a promising tool for investigating individual differences in performance after DBS.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is successful in patients with advanced Parkinson's disease (PD) but may worsen cognitive outcome, including facial emotion recognition (FER). Data‐analyses on 59 consecutive PD patients with complete pre‐ and postoperative assessments, using a sensitive FER test, showed no changes in FER 1 year after STN‐DBS surgery, both after group and individual analyses. These findings do however not exclude the impact of FER in and on itself on the outcome after STN‐DBS. [ABSTRACT FROM AUTHOR]

Background To investigate whether structural network disconnectivity is associated with parkinsonian signs and their progression, as well as with an increased risk of incident parkinsonism. Methods In a prospective cohort (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study) consisting of 293 participants with small vessel disease (SVD), we assessed parkinsonian signs and incident parkinsonism over an 8-year follow-up. In addition, we reconstructed the white matter network followed by graph-theoretical analyses to compute the network metrics. Conventional magnetic resonance imaging markers for SVD were assessed. Results We included 293 patients free of parkinsonism at baseline (2011), with a mean age 68.8 (standard deviation [ SD ] 8.4) years, and 130 (44.4%) were men. Nineteen participants (6.5%) developed parkinsonism during a median (SD) follow-up time of 8.3 years. Compared with participants without parkinsonism, those with all-cause parkinsonism had higher Unified Parkinson's Disease Rating scale (UPDRS) scores and lower global efficiency at baseline. Baseline global efficiency was associated with UPDRS motor scores in 2011 (β = −0.047, p  < .001) and 2015 (β = −0.84, p  < .001), as well as with the changes in UPDRS scores during the 4-year follow-up (β = −0.63, p  = .004). In addition, at the regional level, we identified an inter-hemispheric disconnected network associated with an increased UPDRS motor score. Besides, lower global efficiency was associated with an increased risk of all-cause and vascular parkinsonism independent of SVD markers. Conclusions Our findings suggest that global network efficiency is associated with a gradual decline in motor performance, ultimately leading to incident parkinsonism in the elderly with SVD. Global network efficiency may have the added value to serve as a useful marker to capture changes in motor signs. [ABSTRACT FROM AUTHOR]

Abstract: Motor and cognitive deficits in Parkinson's disease (PD) have been argued to reflect motivational deficits. In prior work, however, we have shown that motivation of cognitive control is paradoxically potentiated rather than impaired in Parkinson's disease. This is particularly surprising given the fact that Parkinson's disease is often accompanied by depression, a prototypical disorder of motivation. To replicate our previous finding and assess the effects of depression, we investigated performance of PD patients with (n = 22) and without depression (history) (n = 23) and age‐matched healthy controls (n = 23) on a task specifically designed to measure the effect of reward motivation on task‐switching. We replicated previous findings by showing contrasting effects of reward motivation on task‐switching in PD patients and age‐matched healthy controls. While the promise of high versus low reward improved task‐switching in PD, it tended to impair task‐switching in age‐matched healthy controls. There were no effects of a depression (history) diagnosis in PD patients. These findings reinforce prior observations that Parkinson's disease is accompanied by enhanced incentive motivation of cognitive control and highlight the potential of incentive motivational strategies for overcoming cognitive deficits in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Differentiating Parkinson's disease and atypical parkinsonism on clinical parameters is challenging, especially in early disease courses. This is due to large overlap in symptoms and because the so called red flags, i.e. symptoms indicating atypical parkinsonism, have not (fully) developed. Brain MRI can aid to improve the accuracy and confidence about the diagnosis. Objective and Methods: In the current paper, we discuss when brain MRI should be performed in the diagnostic work-up of parkinsonism, our preferred brain MRI scanning protocol, and the diagnostic value of specific abnormalities. Results and Conclusions: The main purpose of brain MRI is to assess cerebrovascular damage, and to exclude other possible - and sometimes treatable - causes of parkinsonism, such as normal pressure hydrocephalus. Furthermore, brain MRI can support the possible or probable diagnosis of a specific form of atypical parkinsonism. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (SVD) is a frequent finding on CT and MRI scans of elderly people and is related to vascular risk factors and cognitive and motor impairment, ultimately leading to dementia or parkinsonism in some. In general, the relations are weak, and not all subjects with SVD become demented or get parkinsonism. This might be explained by the diversity of underlying pathology of both white matter lesions (WML) and the normal appearing white matter (NAWM). Both cannot be properly appreciated with conventional MRI. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity. The association between SVD, its microstructural integrity, and incident dementia and parkinsonism has never been investigated. Methods/Design: The RUN DMC study is a prospective cohort study on the risk factors and cognitive and motor consequences of brain changes among 503 non-demented elderly, aged between 50-85 years, with cerebral SVD. First follow up is being prepared for July 2011. Participants alive will be included and invited to the research centre to undergo a structured questionnaire on demographics and vascular risk factors, and a cognitive, and motor, assessment, followed by a MRI protocol including conventional MRI, DTI and resting state fMRI. Discussion: The follow up of the RUN DMC study has the potential to further unravel the causes and possibly better predict the consequences of changes in white matter integrity in elderly with SVD by using relatively new imaging techniques. When proven, these changes might function as a surrogate endpoint for cognitive and motor function in future therapeutic trials. Our data could furthermore provide a better understanding of the pathophysiology of cognitive and motor disturbances in elderly with SVD. The execution and completion of the follow up of our study might ultimately unravel the role of SVD on the microstructural integrity of the white matter in the transition from "normal" aging to cognitive and motor decline and impairment and eventually to incident dementia and parkinsonism. [ABSTRACT FROM AUTHOR]

Introduction: Axial disability, including gait disturbances, is common in Parkinson's disease (PD), especially in advanced stages. Epidural spinal cord stimulation (SCS) has been investigated as a treatment option for gait disorders in PD. Here, we review the literature on SCS in PD and evaluate its efficacy, optimal stimulation parameters, optimal electrode locations, possible effects of concurrent deep brain stimulation, and possible working mechanisms on gait., Methods: Databases were searched for human studies involving PD patients who received an epidural SCS intervention and who had at least one gait-related outcome measure. The included reports were reviewed with respect to design and outcomes. Additionally, the possible mechanisms of action underlying SCS were reviewed., Results: Out of 433 records identified, 25 unique studies with in total 103 participants were included. Most studies included only a few participants. The gait disorders of most PD patients with concurrent pain complaints, mostly low back pain, improved with SCS in almost all cases, regardless of stimulation parameters or electrode location. Higher-frequency stimulation (>200 Hz) seemed to be more effective in pain-free PD patients, but the results were inconsistent. Heterogeneity in outcome measures and follow-up times hindered comparability., Conclusions: SCS may improve gait in PD patients with neuropathic pain, but its efficacy in pain-free patients remains uncertain due to a lack of thorough double-blind studies. Apart from a well-powered, controlled, double-blind study design, future studies could further explore the initial hints that higher-frequency stimulation (>200 Hz) might be the best approach to improve gait outcomes in pain-free patients., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: STN-DBS is a cornerstone in the treatment of advanced Parkinson's disease (PD). The traditional approach is to use an awake operative technique with microelectrode recording (MER). However, more centers start using an asleep MRI-guided technique without MER., Objective: We systematically reviewed the literature to compare STN-DBS surgery with and without MER for differences in clinical outcome., Methods: We systematically searched PubMed, Embase, MEDLINE, and Web of Science databases for randomized clinical trials and consecutive cohort studies published between 01-01-2000 and 26-08-2021, that included at least 10 PD patients who had received bilateral STN-DBS., Results: 2,129 articles were identified. After abstract screening and full-text review, 26 studies were included in the final analysis, comprising a total of 34 study groups (29 MER and 5 non-MER). The standardized mean difference (SMD) in change in motor symptoms between baseline (OFF medication) and 6-24 months follow-up (OFF medication and ON stimulation) was 1.64 for the MER group and 1.87 for non-MER group (p = 0.59). SMD in change in levodopa equivalent daily dose (LEDD) was 1.14 for the MER group and 0.65 for non-MER group (p < 0.01). Insufficient data were available for comparative analysis of PDQ-39 and complications., Conclusion: The change in motor symptoms from baseline to follow-up did not differ between studies that used MER and those that did not. The postoperative reduction in LEDD from baseline to follow-up was greater in the MER-group. In the absence of high-quality studies comparing both methods, there is a clear need for a well-designed comparative trial.

Parkinson's disease (PD) is commonly treated with dopaminergic medication, which enhances some, while impairing other cognitive functions. It can even contribute to impulse control disorder and addiction. We describe the history of research supporting the dopamine overdose hypothesis, which accounts for the large within-patient variability in dopaminergic medication effects across different tasks by referring to the spatially non-uniform pattern of dopamine depletion in dorsal versus ventral striatum. However, there is tremendous variability in dopaminergic medication effects not just within patients across distinct tasks, but also across different patients. In the second part of this chapter we review recent studies addressing the large individual variability in the negative side effects of dopaminergic medication on functions that implicate dopamine, such as value-based learning and choice. These studies begin to unravel the mechanisms of dopamine overdosing, thus revising the strict version of the overdose hypothesis. For example, the work shows that the canonical boosting of reward-versus punishment-based choice by medication is greater in patients with depression and a non-tremor phenotype, which both implicate, among other pathology, more rather than less severe dysregulation of the mesolimbic dopamine system. Future longitudinal cohort studies are needed to identify how to optimally combine different clinical, personality, cognitive, neural, genetic and molecular predictors of detrimental medication effects in order to account for as much of the relevant variability as possible. This will provide a useful tool for precision neurology, allowing individual and contextual tailoring of (the dose of) dopaminergic medication in order to maximize its cognitive benefits, yet minimize its side effects., Competing Interests: Conflict of interest R.C. is a consultant for Roche Ltd, but receives no royalties., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) has become a cornerstone in the advanced treatment of Parkinson's disease (PD). Despite its well-established clinical benefit, there is a significant variation in the way surgery is performed. Most centers operate with the patient awake to allow for microelectrode recording (MER) and intraoperative clinical testing. However, technical advances in MR imaging and MRI-guided surgery raise the question whether MER and intraoperative clinical testing still have added value in DBS-surgery., Objective: To evaluate the added value of MER and intraoperative clinical testing to determine final lead position in awake MRI-guided and stereotactic CT-verified STN-DBS surgery for PD., Methods: 29 consecutive patients were analyzed retrospectively. Patients underwent awake bilateral STN-DBS with MER and intraoperative clinical testing. The role of MER and clinical testing in determining final lead position was evaluated. Furthermore, interobserver variability in determining the MRI-defined STN along the planned trajectory was investigated. Clinical improvement was evaluated at 12 months follow-up and adverse events were recorded., Results: 98% of final leads were placed in the central MER-track with an accuracy of 0.88±0.45 mm. Interobserver variability of the MRI-defined STN was 0.84±0.09. Compared to baseline, mean improvement in MDS-UPDRS-III, PDQ-39 and LEDD were 26.7±16.0 points (54%) (p < 0.001), 9.0±20.0 points (19%) (p = 0.025), and 794±434 mg/day (59%) (p < 0.001) respectively. There were 19 adverse events in 11 patients, one of which (lead malposition requiring immediate postoperative revision) was a serious adverse event., Conclusion: MER and intraoperative clinical testing had no additional value in determining final lead position. These results changed our daily clinical practice to an asleep MRI-guided and stereotactic CT-verified approach.

Introduction: Parkinson's disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging an early diagnosis. Diagnostic accuracy is important because PD and MSA have a different prognosis and response to treatment. Here, we aimed to evaluate the diagnostic value of brain-specific structural proteins in cerebrospinal fluid (CSF) of PD and MSA patients, as well as their association with cognitive decline., Methods: CSF samples were collected from patients with clear signs of parkinsonism, but with uncertain diagnosis at the time of inclusion. Clinical diagnoses of PD (n = 55) and MSA (n = 22) were established after 3 and 10 years of follow-up and re-evaluated after 12 years, according to the most updated clinical criteria. CSF from controls (n = 118) was studied for comparison. Neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B) and myelin basic protein (MBP) levels in CSF were measured using ELISA. Protein levels were also correlated with cognitive decline, i.e. worsening of the mini mental state examination (MMSE) over a period of three years., Results: MBP concentrations were increased in MSA compared to PD and controls (p < 0.005) and could differentiate MSA and PD with high accuracy (AUC = 0.781; p < 0.001). Concentrations of MPB, GFAP and S100B, but not NSE, were significantly elevated in PD patients compared to controls (p = 0.05). None of the brain-specific structural proteins correlated with MMSE progression., Conclusions: Our results demonstrate that MBP differentiates PD from MSA at early stages of the disease, indicating that demyelination and axonal damage may already occur in early stages of MSA., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Deep Brain Stimulation (DBS) is an effective intervention for Parkinson's disease if drug therapy with dopaminergic medication has become insufficient. Current post-operative care focuses on optimizing the neurostimulator in combination with medication. We believe that the success rate of DBS surgery can be enhanced if more attention is paid to the (psychosocial) adjustment problems of patients and their families. Finding a new balance after surgery, in the relationship, family and work, is not easy and can be complicated by postoperative non-motor changes. Care for psychosocial adjustment may improve the quality of life and as such increase the overall outcome after surgery. We present two cases to illustrate these psychosocial adjustment problems. One case describes the impact of stimulation-related behavioural changes on relationships, while the other case describes difficulties in resuming work despite successful surgery. Psychosocial support appeared helpful for both cases to find their new balance in life.