Genetics of Neurogenic Orthostatic Hypotension in Parkinson's Disease, Results from a Cross-Sectional In Silico Study.

The genetic basis of Neurogenic Orthostatic Hypotension (NOH) in Parkinson's disease (PD) has been inadequately explored. In a cross-sectional study, we examined the association between NOH and PD-related single-nucleotide polymorphisms (SNPs) and mapped their effects on gene expression and metabolic and signaling pathways. Patients with PD, free from pathological conditions associated with OH, and not taking OH-associated medications were included. NOH was defined as per international guidelines. Logistic regression was used to relate SNPs to NOH. Linkage-disequilibrium analysis, expression quantitative trait loci, and enrichment analysis were used to assess the effects on gene expression and metabolic/signaling pathways. We included 304 PD patients in the study, 35 of whom had NOH (11.5%). NOH was more frequent in patients with SNPs in SNCA, TMEM175, FAM47E-STBD1, CCDC62, SCN3A, MIR4696, SH3GL2, and LZTS3/DDRGK1 and less frequent in those with SNPs in ITGA8, IP6K2, SIPA1L2, NDUFAF2. These SNPs affected gene expression associated with the significant hierarchical central structures of the autonomic nervous system. They influenced several metabolic/signaling pathways, most notably IP3/Ca++ signaling, the PKA-CREB pathway, and the metabolism of fatty acids. These findings provide new insights into the pathophysiology of NOH in PD and may provide targets for future therapies.

Disproportionality analysis of adverse neurological and psychiatric reactions with the ChAdOx1 (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in the United Kingdom.

BACKGROUND: Information on neurological and psychiatric adverse events following immunization (AEFIs) with COVID-19 vaccines is limited. RESEARCH DESIGN & METHODS: We examined and compared neurological and psychiatric AEFIS reports related to BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines and recorded in the United Kingdom Medicines and Healthcare products Regulatory Agency between 9 December 2020 and 30 June 2021. RESULTS: As of 30 June 2021, 46.1 million doses of ChAdOx1 and 30.3 million doses of BNT162b2 had been administered. The most frequently reported AEFI was headache with 1,686 and 575 cases per million doses of ChAdOx1 and BNT162b2, respectively. AEFIs more frequently reported after CHAdOx1 compared with BNT162b2 vaccination were Guillain-Barré syndrome (OR, 95% CI = 2.53, 1.82-3.51), freezing (6.66, 3.12-14.22), cluster headache (1.53, 1.28-1.84), migraine (1.23,1.17-1.30), postural dizziness (1.24,1.13-1.37), tremor (2.86, 2.68-3.05), headache (1.40, 1.38-1.43), paresthesia (1.11, 1.06-1.16), delirium (1.85, 1.45-2.36), hallucination (2.20, 1.82-2.66), poor quality sleep (1.53, 1.26-1.85), and nervousness (1.54, 1.26-1.89) Reactions less frequently reported with ChAdOx1 than with BNT162b2 were Bell's palsy (0.47, 0.41-0.55), anosmia (0.58, 0.47-0.71), facial paralysis (0.35, 0.29-0.41), dysgeusia (0.68, 0.62-0.73), presyncope (0.48, 0.42-0.55), syncope (0.63, 0.58-0.67), and anxiety (0.75 (0.67-0.85). CONCLUSION: Neurological and psychiatric AEFIs were relatively infrequent, but each vaccine was associated with a distinctive toxic profile.

We examined reports on adverse neurological and psychiatric effects following immunization with BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) for COVID-19 to the United Kingdom Medicines and Healthcare products Regulatory Agency between 9 December 2020 and 30 June 2021. Adverse effects following immunization (AEFIs) were relatively infrequent. Compared to BNT162b2, Guillain-Barré syndrome, freezing phenomenon, cluster headache, migraine, postural dizziness, tremor, headache, paresthesia, delirium, hallucination, poor quality sleep, and nervousness were more frequently reported for ChAdOx1. Reactions less frequently reported for ChAdOx1 than for BNT162b2 were Bell's palsy, anosmia, facial paralysis, dysgeusia, presyncope, syncope, and anxiety.

Parkinson's Disease Medication Adherence Scale: Conceptualization, Scale Development, and Clinimetric Testing Plan.

Background: Medication adherence is a crucial component in the management of patients with chronic diseases needing a long-term pharmacotherapy. Parkinson's disease (PD) is a chronic, degenerative disease with complex drug treatment that poses challenging barriers to patient adherence. The adoption of best practices of scale development can contribute to generate solid concepts and, in the long run, a more stable knowledge base on the underlying constructs of medication adherence in PD measured by the items of the first scale to be created for this purpose. Purpose: To present the development process and clinimetric testing plan of the Parkinson's Disease Medication Adherence Scale (PD-MAS). Method: We adopted a hybrid approach plan based on the United States Food and Drug Administration and Benson and Clark Guide that will create a patient-reported outcome instrument. We presented an overview of consecutive and interrelated steps, containing a concise description of each one. International research centers from Brazil and United States were initially involved in the planning and implementation of the methodological steps of this study. Results: We developed a four-phase multimethod approach for the conceptualization and the clinimetric testing plan of the PD-MAS. First, we describe the development process of the conceptual framework of the PD-MAS underpinning the scale construct; second, we formalized the development process of the first version of the PD-MAS from the generation of item pools to the content validation and pre-testing; third, we established the steps for the first pilot testing and revision; fourth, we describe the steps plan for the first pilot testing and revision, to finally describe its clinimetric testing plan and validation. Conclusion: The overview presentation of the development phases and the clinimetric testing plan of the PD-MAS demonstrate the feasibility of creating an instrument to measure the multidimensional and multifactorial components of the medication adherence process in people with PD.

Rating scales for medication adherence in people living with Parkinson's disease: a systematic review protocol.

OBJECTIVE: The objective of the review is to evaluate the measurement properties of rating scales that have been used to assess the components of medication adherence in patients with Parkinson's disease. INTRODUCTION: Drug therapy is a central strategy in the control of Parkinson's disease symptoms. Measuring behaviors related to medication adherence in patients with Parkinson's disease is vital to understanding the therapeutic response. Consequently, it is necessary to define which instrument offers the most reliable and valid screening. INCLUSION CRITERIA: This review will consider studies in English and Portuguese using structured rating scales to assess medication adherence in people with Parkinson's disease. Studies including data from patients with different diseases in addition to Parkinson's disease will be included only if data are clearly available for each disorder covered. Study protocols, letters to the editors, reviews, and studies with clinical judgment scales but no operationally defined anchor points will be excluded. METHODS: A three-step search strategy will be utilized. Databases will include MEDLINE (PubMed), LILACS (BVS Portal), PsycINFO (APA PsycNet), CINAHL (EBSCO), Web of Science (Clarivate Analytics), Embase, and Scopus (Elsevier). The search strategy will be presented using a PRISMA flow diagram. Eligible studies will be critically appraised for methodological quality using the COSMIN Risk of Bias checklist. Criteria for good measurement properties of the selected scales will be summarized narratively using COSMIN, the Movement Disorder Society Rating Scale Program Committee methodology, the World Health Organization concepts, and the ABC taxonomy of medication adherence. The certainty of the evidence will be determined using the modified GRADE recommendations. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42021211099).

Item Response Theory Analysis of the MDS-UPDRS Motor Examination: Tremor vs. Nontremor Items.

BACKGROUND: In PD, tremor severity behaves differently from other core motor features. However, the most commonly used assessment of overall motor severity, total MDS-UPDRS Motor Examination (Part 3) score, does not account for this distinction. OBJECTIVES: To investigate the Motor Examination (Part 3) using Item Response Theory approaches focusing on sample-independent strategies that assess how well items measure latent models of PD motor severity. METHODS: Data from 6,298 PD patients were analyzed with graded response model Item Response Theory approaches involving two analyses all 33 Part 3 items versus the 10 tremor items and 23 bradykinesia, rigidity, gait, and posture items considered separately. The strength of relationship between items and the latent measure of parkinsonian motor severity (discrimination parameter) and calculated thresholds (location parameters) were assessed using the mirt program implemented in R (R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Analyzing all Part 3 items together, nontremor items demonstrated good discrimination parameters (mean = 1.83 ± 0.37) and range of thresholds (-1.73 to +4.42), but tremor items had poor discrimination (mean = 0.52 ± 0.76) and thresholds (-0.69 to 14.29). Segregating nontremor from tremor items in two independent analyses provided markedly improved discrimination and location parameters for both. CONCLUSIONS: MDS-UPDRS Part 3 tremor and nontremor items have very different relations to the construct of PD severity. Strongly improved clinimetric properties for Part 3 are obtained when tremor and nontremor items are considered separately. We suggest that evaluating PD motor severity, as an operationalized summary measure, is best attained through separate analyses with tremor and nontremor motor scores. © 2020 International Parkinson and Movement Disorder Society.

Babinski's contributions to cerebellar symptomatology: building the basis of the neurological examination.

Several assumptions about the function of the cerebellum and semiotic signs have been described over the centuries. Among the long list of famous researchers who have provided a strong contribution and who have left their names on the highway of cerebellar research, Joseph Babinski appears as a prominent name. The description of various forms of cerebellar symptomatology was a major part of Babinski's work, and clinical terms that he introduced, namely hypermetry , diadochokinesia , and asynergy , remain part of contemporary clinical vocabulary. Babinski studied cerebellar signs in many patients and was able to conduct longitudinal studies that permitted him to understand the evolution of cerebellar dysfunction. Babinski contributions to cerebellar symptomatology continue to influence the most modern theories, including functional and neuropathological studies.

Babinski's contributions to cerebellar symptomatology: building the basis of the neurological examination / As contribuicoes de Babinski para os sinais cerebelares: construindo as bases do exame neurologico

Several assumptions about the function of the cerebellum and semiotic signs have been described over the centuries. Among the long list of famous researchers who have provided a strong contribution and who have left their names on the highway of cerebellar research, Joseph Babinski appears as a prominent name. The description of various forms of cerebellar symptomatology was a major part of Babinski's work, and clinical terms that he introduced, namely hypermetry , diadochokinesia , and asynergy , remain part of contemporary clinical vocabulary. Babinski studied cerebellar signs in many patients and was able to conduct longitudinal studies that permitted him to understand the evolution of cerebellar dysfunction. Babinski contributions to cerebellar symptomatology continue to influence the most modern theories, including functional and neuropathological studies.

Diversas teorias sobre a função do cerebelo e a semiologia dos sinais cerebelares têm sido descritas ao longo dos séculos. Dentre a longa lista de pesquisadores renomados que apresentaram importantes contribuições nesse assunto e que deixaram seus nomes na história, Joseph Babinski aparece com destaque. A descrição dos mais variados sintomas e sinais cerebelares foi peça importante do trabalho de Babinski e algumas nomenclaturas introduzidas por ele, tais como hipermetria , disdiadococinesia e assinergia , continuam a fazer parte do vocabulário contemporâneo. Babinski estudou os sinais cerebelares em muitos pacientes e foi capaz de realizar pesquisas que lhe permitiram compreender a disfunção cerebelar. As contribuições de Babinski para a caracterizar a sintomatologia cerebelar continuam a influenciar as teorias mais modernas, a despeito de estudos funcionais e neuropatológicos.