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Parkinson’s disease (PD) is an age-related neurological disorder known for the observational differences in its risk, progression, and severity between men and women. While estrogen has been considered to be a protective factor in the development of PD, there is little known about the role that fluctuations in hormones and immune responses from sex-specific health experiences have in the disease’s development and severity. We sought to identify women-specific health experiences associated with PD severity, after adjusting for known PD factors, by developing and distributing a women-specific questionnaire across the United States and creating multivariable models for PD severity. We created a questionnaire that addresses women’s specific experiences and their PD clinical history and deployed it through The Parkinson’s Foundation: PD Generation. To determine the association between women-specific health factors and PD severity, we constructed multivariable logistic regression models based on the MDS-UPDRS scale and the participants’ questionnaire responses, genetics, and clinical data. For our initial launch in November 2021, we had 304 complete responses from PD GENEration. Univariate and multivariate logistic modeling found significant associations between major depressive disorder, perinatal depression, natural childbirth, LRRK2 genotype, B12 deficiency, total hysterectomy, and increased PD severity. This study is a nationally available questionnaire for women’s health and PD. It shifts the paradigm in understanding PD etiology and acknowledging how sex-specific experiences may contribute to PD severity. In addition, the work in this study sets the foundation for future research to investigate the factors behind sex differences in PD.

Genetic testing for Parkinson’s disease (PD) is infrequently performed due to perceptions of low utility. We investigated the personal utility in PD GENEration and how results lead to enrollment in additional research studies. Participants ( n  = 972) underwent genetic testing, results disclosure, genetic counseling, and completed a survey examining the perceived personal utility of their results and interest in participating in additional studies. Most participants found their genetic test results useful, including satisfying curiosity (81%), feeling good about helping the medical community (80%), and having information to share with family (77%). There were no significant differences in responses based on result type. Forty-five percent of participants expressed interest in participating in research studies; whereas 16% of participants confirmed enrollment. Our results suggest that participants find personal utility in genetic testing regardless of results. Although participants may be interested in enrolling in additional research, they may need support and resources.

The LRRK2 G2019S pathogenic mutation causes LRRK2-associated Parkinson’s disease (L2PD) with incomplete penetrance. LRRK2 non-manifesting carriers (L2NMC) are at PD high risk but predicting pheno-conversion is challenging given the lack of progression biomarkers. To investigate novel biomarkers for PD premotor stages, we performed a longitudinal microRNA (miRNA) assessment of serum samples from G2019S L2NMC followed-up over 8 years. Our cohort consisted of G2019S L2NMC stratified by dopamine transporter single-photon emission computed tomography (DaT-SPECT) into DaT-negative ( n  = 20) and DaT-positive L2NMC ( n  = 20), pheno-converted G2019S L2PD patients ( n  = 20), idiopathic PD (iPD) ( n  = 19), and controls ( n  = 40). We also screened a second cohort of L2PD patients ( n  = 19) and controls ( n  = 20) (Total n  = 158). Compared to healthy controls, we identified eight deregulated miRNAs in DaT-negative L2NMC, six in DaT-positive L2NMC, and one in L2PD. Between groups, the highest miRNA differences, 24 candidate miRNAs, occurred between DaT-positive L2NMC and L2PD. Longitudinally, we found 11 common miRNAs with sustained variation in DaT-negative and DaT-positive L2NMCs compared to their baselines. Our study identifies novel miRNA alterations in premotor stages of PD co-occurring with progressive DaT-SPECT decline before motor manifestation, whose deregulation seems to attenuate after the diagnosis of L2PD. Moreover, we identified four miRNAs with relatively high discriminative ability (AUC = 0.82) between non-pheno-converted DaT-positive G2019S carriers and pheno-converted L2PD patients (miR-4505, miR-8069, miR-6125, and miR-451a), which hold potential as early progression biomarkers for PD.

Despite data supporting the rapid adoption of telehealth in the delivery of clinical care in North America, the implementation of telehealth visits in clinical research studies has faced critical barriers. These challenges include: (1) variations in state licensure requirements for telehealth; (2) disparities in access to telehealth among disadvantaged populations; (3) lack of consistency among individual Investigational Review Boards (IRBs). Each barrier prevents the systematic conversion of research protocols to include telehealth visits. The Parkinson’s Foundation and members of the Parkinson Study Group submit this Comment to highlight current challenges to implementing telehealth visits for clinical research studies. Our objective is to provide a consensus statement emphasizing the urgent need for regulators to standardize adoption of telehealth practices and to propose recommendations to reduce the burden for implementation in existing research study protocols.

Purpose of ReviewTo describe current practices and attitudes about genetic testing for Parkinson’s disease (PD) among neurologists, highlight the changing scene of genetic testing for PD, and provide guidance on facilitating PD genetic testing in a clinical practice.Recent FindingsSince the 1990s, researchers have discovered several major gene variants contributing to PD etiology. A large body of literature now exists supporting the frequency of these variants in different populations and their effects on phenotype and clinical course. Recently, clinical trials have emerged with therapies targeting genetic forms of PD, specifically LRRK2 and GBA. Despite this growing knowledge, genetic testing for PD is not typically offered by neurologists including movement disorder specialists. Neurologists express concerns about the financial and practical issues of genetic testing as well as the potential impact on their patients. Researchers and specialists in the field are questioning this hesitation as clinical utility and consumer demand increase.SummaryConsideration of genetic testing for PD is shifting, as we enter a new era of precision medicine and gain clinical knowledge about PD. Barriers to testing, as perceived by clinicians, can be overcome with education, support, and involvement of multiple stakeholders with the goal of making PD genetic testing accessible to all patients.

Genetic testing for Parkinson disease (PD) has not been widely used in clinical practice. In preparation for upcoming precision medicine–designed clinical trials for GBA and LRRK2, we evaluated movement disorders specialists’ current practice, knowledge, attitudes, and barriers to genetic testing in PD. An anonymous questionnaire was sent to movement disorders specialists at 146 Parkinson Study Group (PSG) sites in the United States (n = 131) and Canada (n = 15) to assess their knowledge and attitudes about genetic testing for PD. One hundred seventy-eight (47.6%) PSG clinicians completed the questionnaire. Forty-one percent of respondents had not referred any PD patients for genetic testing in the last year and >80% reported referring fewer than 11 patients over the same period. Most common reasons for not referring for genetic testing included lack of insurance coverage/cost to the patient and lack of perceived utility. On a scale of 0–100, the mean level of comfort in respondents’ own ability to genetically counsel PD patients on GBA and LRRK2 was 52 (SD = 28). Sixty percent of clinicians correctly answered all questions about the inheritance and penetrance of GBA and LRRK2 variants. There is an urgent need to increase knowledge and reduce practical barriers to genetic counseling and testing in PD.

Objective The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker‐defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease‐modifying therapeutic trials. Methods A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS‐UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α‐synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t‐tau (45/53) and p‐tau (16/18) were reduced in PD versus HC (P < 0.01), Interpretation PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

Portosystemic encephalopathy commonly occurs in patients with portal hypertension caused by end-stage liver disease or portal vein thrombosis. Congenital extrahepatic portosystemic shunt (CEPS) is an underdiagnosed and treatable condition that can cause encephalopathy and various neuropsychiatric symptoms. We report an unusual case of type 2 CEPS in a 29-year-old woman who presented with progressive myelopathy and fluctuating encephalopathy on a background of congenital cardiac disease. Investigations showed hyperammonaemia, and despite no evidence of portal hypertension on ultrasound imaging, CT scan of abdomen showed a shunt between the mesenteric and left internal iliac veins. Patients with unexplained fluctuating or progressive neuropsychiatric symptoms should have their serum ammonia checked. A raised serum ammonia concentration without known portal hypertension should prompt further investigations for extrahepatic shunts.

PurposeGenetic testing for Parkinson disease (PD) has not been widely used in clinical practice. In preparation for upcoming precision medicine–designed clinical trials for GBA and LRRK2, we evaluated movement disorders specialists’ current practice, knowledge, attitudes, and barriers to genetic testing in PD.MethodsAn anonymous questionnaire was sent to movement disorders specialists at 146 Parkinson Study Group (PSG) sites in the United States (n = 131) and Canada (n = 15) to assess their knowledge and attitudes about genetic testing for PD.ResultsOne hundred seventy-eight (47.6%) PSG clinicians completed the questionnaire. Forty-one percent of respondents had not referred any PD patients for genetic testing in the last year and >80% reported referring fewer than 11 patients over the same period. Most common reasons for not referring for genetic testing included lack of insurance coverage/cost to the patient and lack of perceived utility. On a scale of 0–100, the mean level of comfort in respondents’ own ability to genetically counsel PD patients on GBA and LRRK2 was 52 (SD = 28). Sixty percent of clinicians correctly answered all questions about the inheritance and penetrance of GBA and LRRK2 variants.ConclusionsThere is an urgent need to increase knowledge and reduce practical barriers to genetic counseling and testing in PD.

Membership of the Royal College of Physicians (MRCP) is compulsory for Internal Medical Trainees (IMTs) moving into higher specialty training. The practical component of MRCP – the PACES (Practical Assessment of Clinical Examination Skills) exam – requires extensive preparation. No structured PACES teaching programme existed at St Helier Hospital, UK. In the authors’ experience, local PACES preparation courses are often organised by those who themselves sat the exam many years ago, whereas trainees with recent exam experience are in an excellent position when it comes to providing preparation support.The authors, at the time all IMTs with recent PACES experience, designed and delivered a teaching programme over a three-month period. The course consisted of weekly bedside and simulated teaching sessions tailored to candidates’ specific needs, and a pan-London mock PACES exam to give candidates the opportunity to practise their skills in an environment closely resembling the real-life experience.Direct feedback was obtained both pre and post course, and following each individual session. Questions focussed on such issues as ease of access to PACES teaching and perceived exam preparedness. Pre-course feedback indicated that 86% of candidates felt teaching was difficult to obtain, whereas post course 100% felt this was now easily available. Perceived preparedness across all stations increased from 2.3-3.9 on a 10-point scale pre-course, to 7.8-8.7/10 post-course.The success of this project stressed the importance of realising that leadership is not so much a matter of seniority as it is of experience. Having only recently sat the exam themselves, the authors were in a unique position to identify the needs of PACES candidates and lead a successful preparation programme. Not only is this beneficial for exam candidates; it offers junior trainees the opportunity to develop and display leadership skills that will prove invaluable throughout the rest of their careers.