Deep brain stimulation of symptom-specific networks in Parkinson's disease.

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient.

Electrophysiological sweet spot mapping in deep brain stimulation for Parkinson's disease patients.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) is a well-established therapy to treat Parkinson's disease (PD). However, the STN-DBS sub-target remains debated. Recently, a white matter tract termed the hyperdirect pathway (HDP), directly connecting the motor cortex to STN, has gained interest as HDP stimulation is hypothesized to drive DBS therapeutic effects. Previously, we have investigated EEG-based evoked potentials (EPs) to better understand the neuroanatomical origins of the DBS clinical effect. We found a 3-millisecond peak (P3) relating to clinical benefit, and a 10-millisecond peak (P10) suggesting nigral side effects. Here, we aimed to investigate the neuroanatomical origins of DBS EPs using probabilistic mapping. METHODS: EPs were recorded using EEG whilst low-frequency stimulation was delivered at all DBS-contacts individually. Next, EPs were mapped onto the patients' individual space and then transformed to MNI standard space. Using voxel-wise and fiber-wise probabilistic mapping, we determined hotspots/hottracts and coldspots/coldtracts for P3 and P10. Topography analysis was also performed to determine the spatial distribution of the DBS EPs. RESULTS: In all 13 patients (18 hemispheres), voxel- and fiber-wise probabilistic mapping resulted in a P3-hotspot/hottract centered on the posterodorsomedial STN border indicative of HDP stimulation, while the P10-hotspot/hottract covered large parts of the substantia nigra. CONCLUSION: This study investigated EP-based probabilistic mapping in PD patients during STN-DBS, revealing a P3-hotspot/hottract in line with HDP stimulation and P10-hotspot/hottract related to nigral stimulation. Results from this study provide key evidence for an electrophysiological measure of HDP and nigral stimulation.

Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with [18F]PI-2620.

We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e., fusiform gyrus and crus-cerebellum) were significantly associated with symptom severity and disease duration. This establishes, for the first time to our knowledge, the suitability of [18F]PI-2620 for tracking disease progression in this 4-repeat disease population. This is an important step toward increased clinical utility, such as patient stratification and monitoring in disease-modifying treatment trials. Additionally, the applied methodology successfully optimized reference regions for automated detection of brain imaging tracers. This approach may also hold value for other brain imaging tracers.

[How the implementation of a school for people with Parkinson's disease can succeed-Results of a consensus study and a formative evaluation]. / Wie die Umsetzung einer Schule für Menschen mit Parkinson-Krankheit gelingen kann ­ Ergebnisse eines Konsensusverfahrens und einer formativen Evaluation.

BACKGROUND: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making. MATERIAL AND METHODS: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis. RESULTS: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents. DISCUSSION: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers.

A Retrospective Comparison of Multiple Approaches to Anatomically Informed Contact Selection in Subthalamic Deep Brain Stimulation for Parkinson's Disease.

Background: Conventional deep brain stimulation (DBS) programming via trial-and-error warrants improvement to ensure swift achievement of optimal outcomes. The definition of a sweet spot for subthalamic DBS in Parkinson's disease (PD-STN-DBS) may offer such advancement. Objective: This investigation examines the association of long-term motor outcomes with contact selection during monopolar review and different strategies for anatomically informed contact selection in a retrospective real-life cohort of PD-STN-DBS. Methods: We compared contact selection based on a monopolar review (MPR) to multiple anatomically informed contact selection strategies in a cohort of 28 PD patients with STN-DBS. We employed a commercial software package for contact selection based on visual assessment of individual anatomy following two predefined strategies and two algorithmic approaches with automatic targeting of either the sensorimotor STN or our previously published sweet spot. Similarity indices between chronic stimulation and contact selection strategies were correlated to motor outcomes at 12 months follow-up. Results: Lateralized motor outcomes of chronic DBS were correlated to the similarity between chronic stimulation and visual contact selection targeting the dorsal part of the posterior STN (rho = 0.36, p = 0.007). Similar relationships could not be established for MPR or any of the other investigated strategies. Conclusions: Our data demonstrates that a visual contact selection following a predefined strategy can be linked to beneficial long-term motor outcomes in PD-STN-DBS. Since similar correlations could not be observed for the other approaches to anatomically informed contact selection, we conclude that clear definitions and prospective validation of any approach to imaging-based DBS-programming is warranted.

Preoperative motor deficits and depressive symptoms predict quality of life in patients with Parkinson's disease at different time points after surgery for subthalamic stimulation: a retrospective study.

BACKGROUND: While subthalamic nucleus deep brain stimulation (STN-DBS) improves the quality of life (QoL) of patients with Parkinson's disease (PD), the clinical parameters that predict this improvement remain debated. This retrospective study explored whether preoperative motor, cognitive, and affective parameters predict QoL or its components at 6 and 12 months after STN-DBS surgery. METHODS: QoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39) before (baseline), at 6 months (N = 90) and 12 months (N = 63) after STN-DBS surgery. Changes in the PDQ-39 and its subdomains were analysed with Wilcoxon signed-rank tests. In total, seven motor, cognitive, and affective parameters recorded at baseline were used in multiple linear regressions to predict QoL and its subdomains. RESULTS: QoL had improved significantly at six months post STN-DBS surgery. After 12 months, this effect remained significant but was less pronounced. At both time points, significant improvements in mobility, activities of daily living, stigma, and bodily discomfort were present. Correlation and linear regression analyses showed that preoperative QoL status and changes in QoL at 6 and 12 months after surgery were driven by preoperative dopaminergic medication, as well as motor (UPDRS-III medOFF and PIGD-subscore medOFF) and affective (HADS anxiety and depression) symptoms. In contrast, preoperative cognitive performance did not predict QoL at any time point. CONCLUSION: Data show that preoperative motor and affective symptoms drive both QoL baseline status and changes in QoL after STN-DBS surgery. Thus, these clinical parameters need to be assessed appropriately to provide comprehensive presurgical advice to patients suffering from PD.

Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

Directional versus ring-mode deep brain stimulation for Parkinson's disease: protocol of a multi-centre double-blind randomised crossover trial.

BACKGROUND: The effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson's disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson's disease (STEERING) study is to investigate if directional DBS for Parkinson's disease results in a better clinical outcome when compared to ring-mode DBS. METHODS: The STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson's disease, subthalamic nucleus DBS in a 'classic' ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as 'responders' (i.e., patient with a satisfactory effect of ring-mode DBS) or 'non-responder' (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28-66) followed by directional DBS for 56 days (28-66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson's Disease Rating Scale - Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications-Dyskinesia, disease related quality of life measured with the Parkinson's Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants' therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together. DISCUSSION: The STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson's disease DBS patients or if directional DBS should only be used in a case-based approach. TRIAL REGISTRATION: This trial was registered on the Netherlands Trial Register, as trial NL6508 ( NTR6696 ) on June 23, 2017.

Accelerometric Classification of Resting and Postural Tremor Amplitude.

Clinical rating scales for tremors have significant limitations due to low resolution, high rater dependency, and lack of applicability in outpatient settings. Reliable, quantitative approaches for assessing tremor severity are warranted, especially evaluating treatment effects, e.g., of deep brain stimulation (DBS). We aimed to investigate how different accelerometry metrics can objectively classify tremor amplitude of Essential Tremor (ET) and tremor in Parkinson's Disease (PD). We assessed 860 resting and postural tremor trials in 16 patients with ET and 25 patients with PD under different DBS settings. Clinical ratings were compared to different metrics, based on either spectral components in the tremorband or pure acceleration, derived from simultaneous triaxial accelerometry captured at the index finger and wrist. Nonlinear regression was applied to a training dataset to determine the relationship between accelerometry and clinical ratings, which was then evaluated in a holdout dataset. All of the investigated accelerometry metrics could predict clinical tremor ratings with a high concordance (>70%) and substantial interrater reliability (Cohen's weighted Kappa > 0.7) in out-of-sample data. Finger-worn accelerometry performed slightly better than wrist-worn accelerometry. We conclude that triaxial accelerometry reliably quantifies resting and postural tremor amplitude in ET and PD patients. A full release of our dataset and software allows for implementation, development, training, and validation of novel methods.

Botulism after intragastric botulinum toxin injections for weight reduction.

Although-considering the risk-benefit ratio-botulinum neurotoxin A (BoNT/A) is unequivocally recommended to treat severe neurological diseases such as dystonia, this has not yet been determined for its endoscopic intragastric injection aimed at weight reduction in obesity. However, severe adverse effects of intragastric BoNT/A had not yet been reported, prompting some European countries to endorse its (off-label) use and treat patients transnationally. We here present three cases of botulism after intragastric BoNT/A injections for obesity treatment in a Turkish hospital. Patients presented with cranial nerve affection, bulbar symptoms, and descending paresis, and benefited from treatment with BoNT antitoxin and pyridostigmine. We assume that iatrogenic botulism was induced by overdosing in combination with toxin spread via the highly vascularized gastric tissue. Of note, within a few weeks, more than 80 cases of iatrogenic botulism were reported across Europe after identical intragastric BoNT/A injections. These cases demonstrate the risks of BoNT/A injections if they are not applied within the limits of evidence-based medicine. There is a need for international guidelines to define the indication and a safe dosing scheme, especially in the context of medical tourism.

Parkinson's Disease Stigma Questionnaire (PDStigmaQuest): Development and Pilot Study of a Questionnaire for Stigma in Patients with Idiopathic Parkinson's Disease.

BACKGROUND: Stigma is significant in Parkinson's disease (PD). However, no specific tool is available to assess stigma in PD comprehensively. OBJECTIVE: This pilot study aimed to develop and test a stigma questionnaire specific to PD patients (PDStigmaQuest). METHODS: Based on a literature review, clinical experience, expert consensus, and patients' feedback, we developed the preliminary, patient-completed PDStigmaQuest in German language. It included 28 items covering five stigma domains: uncomfortableness, anticipated stigma, hiding, experienced stigma, and internalized stigma. In this pilot study, 81 participants (PD patients, healthy controls, caregivers, and health professionals) were included to investigate the acceptability, feasibility, comprehensibility, and psychometric properties of the PDStigmaQuest. RESULTS: The PDStigmaQuest showed 0.3% missing data points for PD patients and 0.4% for controls, suggesting high data quality. Moderate floor effects, but no ceiling effects were found. In the item analysis, most items met the standard criteria of item difficulty, item variance, and item-total correlation. Cronbach's alpha was > 0.7 for four of five domains. PD patients' domain scores were significantly higher than healthy controls' for uncomfortableness, anticipated stigma, and internalized stigma. Feedback to the questionnaire was predominantly positive. CONCLUSION: Our results indicate that the PDStigmaQuest is a feasible, comprehensive, and relevant tool to assess stigma in PD and helps to understand the construct of stigma in PD further. Based on our results, the preliminary version of the PDStigmaQuest was modified and is currently validated in a larger population of PD patients for use in clinical and research settings.

Low beta-band suppression as a tool for DBS contact selection for akinetic-rigid symptoms in Parkinson's disease.

BACKGROUND: Suppression of pathologically altered activity in the beta-band has previously been suggested as a biomarker for feedback-based neurostimulation in subthalamic deep brain stimulation (STN-DBS) for Parkinson's Disease (PD). OBJECTIVE: To assess the utility of beta-band suppression as a tool for contact selection in STN-DBS for PD. METHODS: A sample of seven PD patients (13 hemispheres) with newly implanted directional DBS leads of the STN were recorded during a standardized monopolar contact review (MPR). Recordings were received from contact pairs adjacent to the stimulation contact. The degree of beta-band suppression for each investigated contact was then correlated to the respective clinical results. Additionally, we have implemented a cumulative ROC analysis, to test the predictive value of beta-band suppression on the clinical efficacy of the respective contacts. RESULTS: Stimulation ramping led to frequency-specific changes in the beta-band, while lower frequencies remained unaffected. Most importantly, our results showed that the degree of low beta-band suppression from baseline activity (stimulation off) served as a predictor for clinical efficacy of the respective stimulation contact. In contrast suppression of high beta-band activity yielded no predictive power. CONCLUSION: The degree of low beta-band suppression can serve as a time-saving, objective tool for contact selection in STN-DBS.

Compensatory articulatory mechanisms preserve intelligibility in prodromal Parkinson's disease.

INTRODUCTION: Dysarthria is highly prevalent in patients with Parkinson's disease (PD) and speech changes have already been detected in patients with prodromal PD on the acoustic level. However, the present study directly tracks underlying articulatory movements with electromagnetic articulography to investigate early speech alterations on the kinematic level in isolated REM sleep behavior disorder (iRBD) and compares them to PD and control speakers. METHODS: Kinematic data of 23 control speakers, 22 speakers with iRBD, and 23 speakers with PD were collected. Amplitude, duration, and average speed of lower lip, tongue tip, and tongue body movements were analyzed. Naive listeners rated the intelligibility of all speakers. RESULTS: Patients with iRBD produced tongue tip and tongue body movements that were larger in amplitude and longer in duration compared to control speakers, while remaining intelligible. Compared to patients with iRBD, patients with PD had smaller, longer and slower tongue tip and lower lip movements, accompanied by lower intelligibility. Thus, the data indicate that the lingual system is already affected in prodromal PD. Furthermore, lower lip and especially tongue tip movements slow down and speech intelligibility decreases if motor impairment is more pronounced. CONCLUSION: Patients with iRBD adjust articulatory patterns to counteract incipient motor detriment on speech to maintain their intelligibility level.

Myofibrillar myopathy: a rare but important differential diagnosis of camptocormia in a patient with Parkinson's Disease.

Here we report on a patient with Parkinson's Disease and camptocormia due to Myofibrillar Myopathy Type 3. By leading the reader through the clinical reasoning process and highlighting the respective red flags we aim to increase the readers' awareness for the differential diagnosis of camptocormia.

Pallidal deep brain stimulation in a patient with nonketotic hyperglycemic hemichorea.

Background: Hyperkinetic movement disorders secondary to brain tissue damage due to hyperglycemia are a rare complication of diabetes mellitus. Nonketotic hyperglycemic hemichorea (NH-HC) is characterized by a rapid onset of involuntary movements after increased serum glucose levels. Case Description: We report on a case of a 62-year-old male patient with a 28-year history of Type II diabetes mellitus with NH-HC following an infect-associated exacerbation of blood glucose levels. Choreiform movements of the right upper extremity, face, and trunk persisted 6 months after onset. Due to failure of conservative treatments, we opted for unilateral deep brain stimulation of the globus pallidus internus, which led to complete cessation of symptoms within a week after initial programming. Symptom control was still satisfactory 12 months after surgery. No side-effects or surgery-associated complications were observed. Conclusion: Globus pallidus internus DBS is an effective and safe treatment option for hyperkinetic movement disorders secondary to brain tissue damage caused by hyperglycemia. Postoperatively, stimulation effects can be observed quickly and effects persist even after 12 months.

Non-motor effects of deep brain stimulation in Parkinson's disease motor subtypes.

INTRODUCTION: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD. METHODS: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests. RESULTS: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores. CONCLUSIONS: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.

Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool.

Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson's disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that α-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of α-synuclein aggregates in stool of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. We measured significantly elevated concentrations of α-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p < 0.001). Our results show that α-synuclein aggregates are excreted in stool and can be measured using the sFIDA assay, which could support the diagnosis of prodromal synucleinopathies.

Internal Capsule/Nucleus Accumbens Deep Brain Stimulation Increases Impulsive Decision Making in Obsessive-Compulsive Disorder.

BACKGROUND: Deep brain stimulation of the anterior limb of the internal capsule (ALIC)/nucleus accumbens is an effective treatment in patients with obsessive-compulsive disorder but may increase impulsive behavior. We aimed to investigate how active stimulation alters subdomains of impulsive decision making and whether respective effects depend on the location of stimulation sites. METHODS: We assessed 15 participants with obsessive-compulsive disorder performing the Cambridge Gambling Task during active and inactive ALIC/nucleus accumbens deep brain stimulation. Specifically, we determined stimulation-induced changes in risk adjustment and delay aversion. To characterize underlying neural pathways, we computed probabilistic stimulation maps and applied fiber filtering based on normative structural connectivity data to identify "hot" and "cold" spots/fibers related to changes in impulsive decision making. RESULTS: Active stimulation significantly reduced risk adjustment while increasing delay aversion, both implying increased impulsive decision making. Changes in risk adjustment were robustly associated with stimulation sites located in the central ALIC and fibers connecting the thalamus and subthalamic nucleus with the medial and lateral prefrontal cortex. Both hot spots and fibers for changes in risk adjustment were robust to leave-one-out cross-validation. Changes in delay aversion were similarly associated with central ALIC stimulation, but validation hereof was nonsignificant. CONCLUSIONS: Our findings provide experimental evidence that ALIC/nucleus accumbens stimulation increases impulsive decision making in obsessive-compulsive disorder. We show that changes in risk adjustment depend on the location of stimulation volumes and affected fiber bundles. The relationship between impulsive decision making and long-term clinical outcomes requires further investigation.

Dermal Real-Time Quaking-Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α-Synucleinopathy.

BACKGROUND: Skin biopsy is a potential tool for the premortem confirmation of an α-synucleinopathy. OBJECTIVE: The aim was to assess the aggregation assay real-time quaking-induced conversion (RT-QuIC) of skin biopsy lysates to confirm isolated rapid eye movement sleep behavior disorder (iRBD) as an α-synucleinopathy. METHODS: Skin biopsies of patients with iRBD, Parkinson's disease (PD), and controls were analyzed using RT-QuIC and immunohistochemical detection of phospho-α-synuclein. RESULTS: α-Synuclein aggregation was detected in 97.4% of iRBD patients (78.4% of iRBD biopsies), 87.2% of PD patients (70% of PD biopsies), and 13% of controls (7.9% of control biopsies), with a higher seeding activity in iRBD compared to PD. RT-QuIC was more sensitive but less specific than immunohistochemistry. CONCLUSIONS: Dermal RT-QuIC is a sensitive method to detect α-synuclein aggregation in iRBD, and high seeding activity may indicate a strong involvement of dermal nerve fibers in these patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Brain Morphometry Associated With Response to Levodopa and Deep Brain Stimulation in Parkinson Disease.

OBJECTIVES: Whether treatment response in patients with Parkinson disease depends on brain atrophy is insufficiently understood. The goal of this study is to identify specific atrophy patterns associated with response to dopaminergic therapy and deep brain stimulation. MATERIALS AND METHODS: In this study, we analyzed the association of gray matter brain atrophy patterns, as identified by voxel-based morphometry, with acute response to levodopa (N = 118) and subthalamic nucleus deep brain stimulation (N = 39). Motor status was measured as a change in points on the Unified Parkinson's Disease Rating Scale III score. Baseline values were obtained before surgery, after cessation of dopaminergic medication for at least 12 hours; response to medication was assessed after administration of a standardized dose of levodopa. Response to deep brain stimulation was measured three months after surgery in the clinical condition after withdrawal of dopaminergic medication. RESULTS: Although frontoparietal brain gray matter loss was associated with subpar response to deep brain stimulation, there was no significant link between brain atrophy and response to levodopa. CONCLUSION: We conclude that response to deep brain stimulation relies on gray matter integrity; hence, gray matter loss may present a risk factor for poor response to deep brain stimulation and may be considered when making decision regarding clinical practice.