Browsing by Subject "Parkinson’s disease"
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Item Open Access Genetics of Neurogenic Orthostatic Hypotension in Parkinson's Disease, Results from a Cross-Sectional In Silico Study.(Brain sciences, 2023-03) Chevalier, Guenson; Udovin, Lucas; Otero-Losada, Matilde; Bordet, Sofia; Capani, Francisco; Luo, Sheng; Goetz, Christopher G; Perez-Lloret, SantiagoThe 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.Item Open Access Proceedings of the Seventh Annual Deep Brain Stimulation Think Tank: Advances in Neurophysiology, Adaptive DBS, Virtual Reality, Neuroethics and Technology.(Frontiers in human neuroscience, 2020-01) Ramirez-Zamora, Adolfo; Giordano, James; Gunduz, Aysegul; Alcantara, Jose; Cagle, Jackson N; Cernera, Stephanie; Difuntorum, Parker; Eisinger, Robert S; Gomez, Julieth; Long, Sarah; Parks, Brandon; Wong, Joshua K; Chiu, Shannon; Patel, Bhavana; Grill, Warren M; Walker, Harrison C; Little, Simon J; Gilron, Ro'ee; Tinkhauser, Gerd; Thevathasan, Wesley; Sinclair, Nicholas C; Lozano, Andres M; Foltynie, Thomas; Fasano, Alfonso; Sheth, Sameer A; Scangos, Katherine; Sanger, Terence D; Miller, Jonathan; Brumback, Audrey C; Rajasethupathy, Priya; McIntyre, Cameron; Schlachter, Leslie; Suthana, Nanthia; Kubu, Cynthia; Sankary, Lauren R; Herrera-Ferrá, Karen; Goetz, Steven; Cheeran, Binith; Steinke, G Karl; Hess, Christopher; Almeida, Leonardo; Deeb, Wissam; Foote, Kelly D; Okun, Michael SThe Seventh Annual Deep Brain Stimulation (DBS) Think Tank held on September 8th of 2019 addressed the most current: (1) use and utility of complex neurophysiological signals for development of adaptive neurostimulation to improve clinical outcomes; (2) Advancements in recent neuromodulation techniques to treat neuropsychiatric disorders; (3) New developments in optogenetics and DBS; (4) The use of augmented Virtual reality (VR) and neuromodulation; (5) commercially available technologies; and (6) ethical issues arising in and from research and use of DBS. These advances serve as both "markers of progress" and challenges and opportunities for ongoing address, engagement, and deliberation as we move to improve the functional capabilities and translational value of DBS. It is in this light that these proceedings are presented to inform the field and initiate ongoing discourse. As consistent with the intent, and spirit of this, and prior DBS Think Tanks, the overarching goal is to continue to develop multidisciplinary collaborations to rapidly advance the field and ultimately improve patient outcomes.Item Open Access The Impact of Environmental Factors on Monogenic Mendelian Diseases.(Toxicological sciences : an official journal of the Society of Toxicology, 2021-03-02) Tukker, Anke M; Royal, Charmaine D; Bowman, Aaron B; McAllister, Kimberly AEnvironmental factors and gene-environment interactions modify the variable expressivity, progression, severity, and onset of some classic (monogenic) Mendelian-inherited genetic diseases. Cystic Fibrosis, Huntington Disease, Parkinson's Disease, and Sickle Cell Disease are examples of well-known Mendelian disorders that are influenced by exogenous exposures. Environmental factors may act by direct or indirect mechanisms to modify disease severity, timing, and presentation, including through epigenomic influences, protein misfolding, miRNA alterations, transporter activity, and mitochondrial effects. Since pathological features of early-onset Mendelian diseases can mimic later onset complex diseases, we propose that studies of environmental exposure vulnerabilities using monogenic model systems of rare Mendelian diseases have high potential to provide insight into complex disease phenotypes arising from multi-genetic/multi-toxicant interactions. Mendelian disorders can be modeled by homologous mutations in animal model systems with strong recapitulation of human disease etiology and natural history, providing an important advantage for study of these diseases. Monogenic high penetrant mutations are ideal for toxicant challenge studies with a wide variety of environmental stressors, since background genetic variability may be less able to alter the relatively strong phenotype driving disease-causing mutations. These models promote mechanistic understandings of gene-environment interactions and biological pathways relevant to both Mendelian and related sporadic complex disease outcomes by creating a sensitized background for relevant environmental risk factors. Additionally, rare disease communities are motivated research participants, creating the potential of strong research allies among rare Mendelian disease advocacy groups and disease registries and providing a variety of translational opportunities that are under-utilized in genetic or environmental health science.Item Open Access Time-varying caloric vestibular stimulation for the treatment of neurodegenerative disease.(Frontiers in aging neuroscience, 2022-01) Black, Robert D; Chaparro, EduardoTime-varying caloric vestibular stimulation (tvCVS) is a new form of non-invasive neuromodulation similar to, but different from, diagnostic caloric vestibular stimulation (CVS). Using a non-invasive, solid-state delivery device, tvCVS has been successfully used in a human clinical trial with Parkinson's disease (PD) subjects. Additionally, the effects of tvCVS on brain activation have been studied in healthy human subjects using transcranial Doppler sonography (TCD) and functional magnetic resonance imaging (BOLD fMRI). A novel finding in the TCD and fMRI studies was the induction of cerebral blood flow velocity (CBFv) oscillations. How such oscillations might lead to the observed clinical effects seen in PD subjects will be discussed. Enabling studies of tvCVS with rodents is an attractive goal in support of explorations of the mechanism of action. Male Wistar rats were used in a proof-of-concept study described herein. Rats were anesthetized (isoflurane) and ventilated for the duration of the tvCVS runs. Time-varying thermal stimuli were administered using a digital temperature controller to modulate Peltier-type heater/cooler devices. Blunt ear bars conveyed the thermal stimulus to the external ear canals of the rats. Different thermal waveform combinations were evaluated for evidence of successful induction of the CVS effect. It was found that bilateral triangular thermal waveforms could induce oscillations in CBFv both during and after the application of tvCVS. These oscillations were similar to, but different from those observed in awake human subjects. The establishment of a viable animal model for the study of tvCVS will augment ongoing clinical investigations of this new form of neuromodulation in patients with neurodegenerative disease.Item Open Access Understanding the Lexicon of Fatigue in Parkinson's Disease.(Journal of Parkinson's disease, 2020-06-15) Mantri, Sneha; Klawson, Emily; Albert, Steven; Nabieva, Karina; Lepore, Madeline; Kahl, Stephen; Daeschler, Margaret; Mamikonyan, Eugenia; Kopil, Catherine; Marras, Connie; Chahine, Lana MBACKGROUND:Fatigue in Parkinson's disease (PD) is multifaceted and associated with reduced quality of life. In turn, the language used by people with PD to describe fatigue is variable and poorly understood. We sought to elucidate the lexicon of fatigue using a qualitative grounded theory approach. OBJECTIVE:The objective of this study was to understand how patients with PD describe fatigue. METHODS:A pre-study phase of online journaling (Phase 1) provided information regarding topics of importance to patients. Following this, two independent samples of fatigued subjects were studied. Individuals with PD participated in a telephone interview (Phase 2); interview transcripts were analyzed to develop a detailed codebook. To ensure trustworthiness of the findings, an online survey (Phase 3) was administered to individuals with self-reported PD participating in the online study Fox Insight. The survey included the following question: "How do you define fatigue? Please provide your definition in the space below." The codebook developed from Phase 2 was applied to the Phase 3 responses. RESULTS:Fifteen individuals participated in Phase 2 and 413 individuals completed Phase 3. Fatigue was subdivided into three domains: cognitive, emotional, and physical. Nearly all individuals experienced more than one domain of fatigue. The most common themes included tiredness, lack of energy, and negative motivation. CONCLUSION:Fatigue in PD is multidimensional. Questionnaires that only assess the physical impact of fatigue may not be adequate to capture the broad range of experiences of fatigue among people with PD.Item Open Access Validation of the Finnish Version of the Unified Dyskinesia Rating Scale.(European neurology, 2021-07-14) Kaasinen, Valtteri; Scheperjans, Filip; Kärppä, Mikko; Korpela, Jaana; Brück, Anna; Sipilä, Jussi OT; Joutsa, Juho; Järvelä, Juha; Eerola-Rautio, Johanna; Martikainen, Mika H; Airaksinen, Katja; Stebbins, Glenn T; Martinez-Martin, Pablo; Goetz, Christopher G; Lin, Jeffrey; Luo, Sheng; Pekkonen, EeroIntroduction
The Unified Dyskinesia Rating Scale (UDysRS) was developed to provide a comprehensive rating tool of dyskinesia in Parkinson's disease (PD). Because dyskinesia therapy trials involve multicenter studies, having a scale that is validated in multiple non-English languages is pivotal to international efforts to treat dyskinesia. The aim of the present study was to organize and perform an independent validation of the UDysRS Finnish version.Methods
The UDysRS was translated into Finnish and then back-translated into English using 2 independent teams. Cognitive pretesting was conducted on the Finnish version and required modifications to the structure or wording of the translation. The final Finnish version was administered to 250 PD patients whose native language is Finnish. The data were analyzed to assess the confirmatory factor structure to the Spanish UDysRS (the reference standard). Secondary analyses included an exploratory factor analysis (EFA), independent of the reference standard.Results
The comparative fit index (CFI), in comparison with the reference standard factor structure, was 0.963 for Finnish. In the EFA, where variability from sample to sample is expected, isolated item differences of factor structure were found between the Finnish and Reference Standard versions of the UDysRS. These subtle differences may relate to differences in sample composition or variations in disease status.Conclusion
The overall factor structure of the Finnish version was consistent with that of the reference standard, and it can be designated as the official version of the UDysRS for Finnish speaking populations.Item Open Access Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.(Neuroepidemiology, 2020-06-15) Faust-Socher, Achinoam; Anis, Saar; Kestenbaum, Meir; Shabtai, Herzl; Taichman, Tali; Bar David, Aya; Ezra, Adi; Peretz, Chava; Rosenberg, Alina; Brozgol, Marina; Herman, Talia; Stebbins, Glenn T; Goetz, Christopher G; Martínez-Martín, Pablo; Luo, Sheng T; Ren, Xuehan; Giladi, Nir; Gurevich, TanyaBACKGROUND:The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS:We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS:The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION:The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.Item Open Access Validation of the Thai Version of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale.(Journal of movement disorders, 2022-03-16) Jagota, Priya; Srivanitchapoom, Prachaya; Petchrutchatachart, Sitthi; Singmaneesakulchai, Surat; Pisarnpong, Apichart; Lolekha, Praween; Setthawatcharawanich, Suwanna; Chairangsaris, Parnsiri; Limotai, Natlada; Mekawichai, Pawut; Panyakaew, Pattamon; Phokaewvarangkul, Onanong; Sringean, Jirada; Pitakpatapee, Yuvadee; LaPelle, Nancy; Martinez-Martin, Pablo; Ren, Xuehan; Luo, Sheng; Stebbins, Glenn T; Goetz, Christopher G; Bhidayasiri, RoongrojObjective
This study aims to validate the Thai translation of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS).Methods
The English version was translated into Thai and then back-translated into English. The translated version underwent 2 rounds of cognitive pretesting to assess the ease of comprehension, ease of use and comfort with the scale. Then, it underwent large clinimetric testing.Results
The Thai version was validated in 354 PD patients. The comparative fit index (CFI) for all four parts of the Thai version of the MDS-UPDRS was 0.93 or greater. Exploratory factor analysis identified isolated item differences in factor structure between the Thai and English versions.Conclusion
The overall factor structure of the Thai version was consistent with that of the English version based on the high CFIs (all CFI ≥ 0.90). Hence, it can be designated the official Thai version of the MDS-UPDRS.