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BackgroundIn 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD.ObjectivesThe objective of this study was to generate and test a PD diagnostic criteria termed "clinically established early PD."MethodsWe modified the Movement Disorder Society criteria to increase specificity for early PD by removing all disease duration components and changing red flags to absolute exclusions. We then estimated the sensitivity/specificity of clinically established early PD criteria in patients with disease duration

Social cognition (SC) encompasses a set of cognitive functions that enable individuals to understand and respond appropriately to social interactions. Although focused ultrasound subthalamotomy (FUS‐STN) effectively treats Parkinson's disease (PD) clinical motor features, its impact and safety on cognitive‐behavioral interactions/interpersonal awareness are unknown. This study investigated the effects of unilateral FUS‐STN on facial emotion recognition (FER) and affective and cognitive theory of mind (ToM) in PD patients from a randomized sham‐controlled trial (NCT03454425). Subjects performed SC evaluation before and 4 months after the procedure while still under blind assessment conditions. The SC assessment included the Karolinska Directed Emotional Faces task for FER, the Reading the Mind in the Eyes (RME) test for affective ToM, and The Theory of Mind Picture Stories Task (ToM PST) (order, questions, and total score) for cognitive ToM. The active treatment group showed anecdotal‐to‐moderate evidence of no worsening in SC after FUS‐STN. Anecdotal evidence for an improvement was recognized in the SC score changes, from baseline to post‐treatment, for the active treatment group compared with sham for the RME, ToM PST order, ToM PST total, FER total, and recognition of fear, disgust, and anger. This study provides the first evidence that unilateral FUS‐STN does not impair social cognitive abilities, indicating that it can be considered a safe treatment approach for this domain in PD patients. Furthermore, the results suggest FUS‐STN may even lead to some improvement in social cognitive outcomes, which should be considered as a preliminary finding requiring further investigation with larger samples sizes. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet possible. Given the lack of clear neuroprotective/disease-modifying therapy for prodromal PD, these criteria were developed for research purposes only. The criteria are based upon the likelihood of prodromal disease being present with probable prodromal PD defined as ≥80% certainty. Certainty estimates rely upon calculation of an individual's risk of having prodromal PD, using a Bayesian naïve classifier. In this methodology, a previous probability of prodromal disease is delineated based upon age. Then, the probability of prodromal PD is calculated by adding diagnostic information, expressed as likelihood ratios. This diagnostic information combines estimates of background risk (from environmental risk factors and genetic findings) and results of diagnostic marker testing. In order to be included, diagnostic markers had to have prospective evidence documenting ability to predict clinical PD. They include motor and nonmotor clinical symptoms, clinical signs, and ancillary diagnostic tests. These criteria represent a first step in the formal delineation of early stages of PD and will require constant updating as more information becomes available.

With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD. This review is a discussion article, intended as the introductory statement of the task force. Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration.

The neural network mediating successful response inhibition mainly includes right hemisphere activation of the pre‐supplementary motor area, inferior frontal gyrus (IFG), subthalamic nucleus (STN), and caudate nucleus. However, the causal role of these regions in the inhibitory network is undefined. Five patients with Parkinson's disease were assessed prior to and after therapeutic thermal ablation of the right STN in two separate functional magnetic resonance imaging (fMRI) sessions while performing a stop‐signal task. Initiation times were faster but motor inhibition with the left hand (contralateral to the lesion) was significantly impaired as evident in prolonged stop‐signal reaction times. Reduced inhibition after right subthalamotomy was associated (during successful inhibition) with the recruitment of basal ganglia regions outside the established inhibitory network. They included the putamen and caudate together with the anterior cingulate cortex and IFG of the left hemisphere. Subsequent network connectivity analysis (with the seed over the nonlesioned left STN) revealed a new inhibitory network after right subthalamotomies. Our results highlight the causal role of the right STN in the neural network for motor inhibition and the possible basal ganglia mechanisms for compensation upon losing a key node of the inhibition network. [ABSTRACT FROM AUTHOR]

Background: Double‐blind studies have demonstrated that motor complications in Parkinson's disease (PD) can be reduced with continuous delivery of levodopa. The DopaFuse system is a novel, intraoral micropump that attaches to a retainer and uses a propellant to deliver levodopa/carbidopa (LD/CD) continuously into the mouth. Objectives: Evaluate the safety, pharmacokinetics, and efficacy of LD/CD delivered via the DopaFuse system compared to treatment with intermittent doses of standard oral LD/CD in PD patients with motor fluctuations. Methods: This was a 2‐week, open‐label study (NCT04778176) in 16 PD patients treated with ≥4 levodopa doses/day and experiencing motor fluctuations. On Day 1 (clinic setting) patients received their usual dose of standard LD/CD; DopaFuse therapy was initiated on Day 2, and on Day 3 patients received DopaFuse plus a morning oral LD/CD dose. Patients returned home on Days 4–14 and returned for in‐clinic assessment on Day 15. Results: Continuous DopaFuse delivery of LD/CD was associated with reduced variability in plasma levodopa levels compared to oral LD/CD (mean ± SD levodopa Fluctuation Index reduced from 2.15 ± 0.59 on Day1 to 1.50 ± 0.55 on Day 2 (P = 0.0129) and to 1.03 ± 0.53 on Day 3 (P < 0.0001)). This pharmacokinetic improvement translated into significantly reduced OFF time with DopaFuse therapy (reduction of −1.72 ± 0.37 h at Day 15; P = 0.0004) and increased ON time without severe dyskinesias (increase of 1.72 ± 0.37 h at Day 15; P = 0.0004) versus oral LD/CD administration. DopaFuse therapy was not associated with any clinically significant adverse events. Conclusions: Continuous delivery of LD/CD using the DopaFuse system was associated with significantly less variability in plasma levodopa concentrations and reductions in OFF time compared to treatment with standard oral LD/CD therapy and was well tolerated. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]