scholarly journals A Patient-Centered Conceptual Model of Symptoms and Their Impact in Early Parkinson’s Disease: A Qualitative Study

2021 ◽  
pp. 1-15
Author(s):  
Hannah Staunton ◽  
Kim Kelly ◽  
Louise Newton ◽  
Mathias Leddin ◽  
Raul Rodriguez-Esteban ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Qualitative Research ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Conceptual Model ◽  
Early Stage ◽  
Patient Centered ◽  
Yahr Stage ◽  
Treatment Benefit ◽  
Concept Elicitation

Background: Individuals with Parkinson’s disease (PD) develop a significant disease burden over time that contributes to a progressive decline in health-related quality of life (HRQoL). There is a paucity of qualitative research to understand symptoms and impacts in individuals with early-stage PD (i.e., Hoehn and Yahr stage 1–2 and ≤2 years since diagnosis). Objective: The collection of qualitative data to inform the selection of clinical outcome assessments for clinical trials is advocated by regulators. This patient-centered, multistage study sought to create a conceptual model of symptoms and their impact for individuals with early-stage PD. Methods: Symptoms and impacts of PD were gathered from a literature review of qualitative research, a quantitative social media listening analysis, and qualitative patient concept elicitation interviews (n = 35). Clinical experts provided input to validate and finalize the concepts. Results: The final conceptual model consisted of 27 symptoms categorized into ‘motor’ or ‘non-motor’ domains, and 39 impacts divided into five domains. Most frequently reported symptoms in early-stage PD were ‘tremors’ (89%), ‘stiffness and rigidity’, and ‘fatigue’ (69%, both). Most frequently reported impacts included ‘anxiety’ (74%), ‘eating and drinking’ (71%), followed by ‘exercise/sport’ and ‘relationship with family/family life’ (66%, both). Conclusion: This study provides initial insights relating to the symptom and impact burden of early-stage PD patients. The conceptual model can be used to help researchers to develop and select optimal patient-centered outcomes to measure treatment benefit in clinical trials. These findings could inform future qualitative research and the development of outcomes specifically for early-stage PD patients.

scholarly journals Unilateral loss of the swallow tail sign in a patient with idiopathic Parkinson’s disease

2021 ◽  
Vol 3 (3) ◽  
pp. 59-62
Author(s):  
Anna Misyail Abd Rashid ◽  
Mohamad Syafeeq Faeez Md Noh ◽  
Abdul Hanif Khan Yusof Khan ◽  
Mohd Naim Mohd Yaakob ◽  
Norafida Bahari ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Predictive Value ◽  
Early Stage ◽  
Imaging Biomarker ◽  
Idiopathic Parkinson’S Disease ◽  
Yahr Stage ◽  
Hand Tremor ◽  
Idiopathic Parkinson's Disease

A 66-year-old man with underlying hypertension and dyslipidemia presented with left hand tremor for one year. He also noticed difficulty in initiating movement and slowness in activities of daily living. On examination, he was noted to have mask-like facies with reduced blinking and monotonous speech. There was presence of resting pill-rolling tremor, bradykinesia, and cogwheel rigidity which was worst on the left upper limb. Gait assessment revealed difficulty in standing up, shuffling gait with reduced arm swing which was more prominent on the left side, and turning in numbers. No cerebellar signs and supranuclear palsy were present to suggest Parkinson-plus syndrome. Susceptibility weighted imaging (SWI) showed loss of the swallow tail sign on the right side [Figure 1]. The clinical presentation, supplemented by the imaging findings were concluded to be pathognomonic of idiopathic Parkinson’s disease (IPD), Hoehn & Yahr stage 1. He was started on levodopa and benserazide twice daily with improvement of symptoms.The nigrosomes are primary subregions of the substantia nigra where dopaminergic cells are lost in IPD. Within these nigrosomes, maximal cell loss occurs in nigrosome-1; the largest subgroup of nigrosomes. Normally, they appear as a SWI-hyperintense area surrounded by hypointensity within the dorsolateral substantia nigra, akin to a swallow’s tail. In one study, poor visualization of nigrosome-1 was significantly associated with higher motor asymmetry in the contralateral side (sensitivity 98.5%, specificity 93.6%, positive-predictive value 98.3%, negative-predictive value 98.3% and an accuracy of 96%) [1]. Noh et al [2] showed that abnormality involving nigrosome-1 can be detected at 3T MR imaging with an accuracy of 94.6%. Due to the difficulty in diagnosis of early stage IPD, a loss of the swallow tail sign serves as a useful imaging biomarker to supplement the clinical diagnosis, as seen in our patient.

scholarly journals FDG PET Parkinson’s disease-related pattern as a biomarker for clinical trials in early stage disease

2018 ◽  
Vol 20 ◽  
pp. 572-579 ◽  
Author(s):  
Dawn C. Matthews ◽  
Hedva Lerman ◽  
Ana Lukic ◽  
Randolph D. Andrews ◽  
Anat Mirelman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Fdg Pet ◽  
Early Stage ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Related Pattern

scholarly journals Postural Instability and Cognitive Dysfunction in Early Parkinson's Disease

2012 ◽  
Vol 39 (4) ◽  
pp. 473-482 ◽  
Author(s):  
Jong Moon Lee ◽  
Seong-Beom Koh ◽  
Sung Won Chae ◽  
Woo-Keun Seo ◽  
Do Young Kwon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Postural Instability ◽  
Sensory Organization Test ◽  
Yahr Stage ◽  
Dynamic Posturography ◽  
Motor Latency ◽  
Sensory Organization ◽  
Computerized Dynamic Posturography

Background:Postural instability is one of the most disabling features of Parkinson's disease, usually occurring in late and advanced stages. The aim of this study was to investigate the postural performance of early-stage de novo Parkinson's disease patients with no clinical postural instability using computerized dynamic posturography. We sought to understand the relationship between postural sway and disease severity and the relationship between postural instability quantitatively measured by computerized dynamic posturography and cognitive impairment in early-stage Parkinson's disease patients.Method:Thirty-one subjects with Parkinson's disease and 20 healthy controls were assessed by the computerized dynamic posturography protocol using the sensory organization test and the motor control test. A neuropsychological assessment was also administered.Results:The mean equilibrium score for sensory organization test and the vestibular input ratio were significantly correlated with Hoehn-Yahr stage. No associations between motor latency for any motor control test condition and Hoehn-Yahr stage were found. The equilibrium score for sensory organization test correlated with the mini-mental status examination scores. There was a significant correlation between motor latency for large backward translation and mini-mental status examination scores. There were significant correlations between visual perception/construction/ memory of the neuropsychological battery test and the equilibrium score for sensory organization test and between verbal word learning test, controlled word association test and motor latency for large backward translation.Conclusion:These findings showed the postural instability present in early-stage (Hoehn-Yahr stage 2-2.5) Parkinson's disease. We also found a close relationship between postural instability and cognitive function in Parkinson's disease patients.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

Gene expression analysis in modeling Parkinson’s disease

2020 ◽  
pp. 103-104
Author(s):  
М.М. Руденок ◽  
А.Х. Алиева ◽  
А.А. Колачева ◽  
М.В. Угрюмов ◽  
П.А. Сломинский ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Systemic Disease ◽  
Molecular Genetic ◽  
Presymptomatic Stage ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
The Brain ◽  
Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

scholarly journals Holistic Metabolomic Laboratory-Developed Test (LDT): Development and Use for the Diagnosis of Early-Stage Parkinson’s Disease

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 14
Author(s):  
Petr G. Lokhov ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Oxana P. Trifonova ◽  
Elena E. Balashova
Keyword(s):  
Parkinson’S Disease ◽  
Molecular Weight ◽  
Parkinson's Disease ◽  
High Resolution Mass Spectrometry ◽  
Early Stage ◽  
Disease Diagnosis ◽  
The Body ◽  
Low Molecular Weight ◽  
Low Molecular Weight Compounds

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is developed and used within a single laboratory. The holistic metabolomic LDT integrating the currently available data on human metabolic pathways, changes in the concentrations of low-molecular-weight compounds in the human blood during diseases and other conditions, and their prevalent location in the body was developed. That is, the LDT uses all of the accumulated metabolic data relevant for disease diagnosis and high-resolution mass spectrometry with data processing by in-house software. In this study, the LDT was applied to diagnose early-stage Parkinson’s disease (PD), which currently lacks available laboratory tests. The use of the LDT for blood plasma samples confirmed its ability for such diagnostics with 73% accuracy. The diagnosis was based on relevant data, such as the detection of overrepresented metabolite sets associated with PD and other neurodegenerative diseases. Additionally, the ability of the LDT to detect normal composition of low-molecular-weight compounds in blood was demonstrated, thus providing a definition of healthy at the molecular level. This LDT approach as a screening tool can be used for the further widespread testing for other diseases, since ‘omics’ tests, to which the metabolomic LDT belongs, cover a variety of them.

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