Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor.
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ABSTRACT:
SUBMITTER: Ostrakhovitch EA
PROVIDER: S-EPMC8996687 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor.
Ostrakhovitch Elena A EA Song Eun-Suk ES Macedo Jessica K A JKA Gentry Matthew S MS Quintero Jorge E JE van Horne Craig C Yamasaki Tritia R TR
Neuroscience letters 20211228
Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted ...[more]
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Project description:Essential tremor (ET) and Parkinson's disease (PD) are among the most common adult-onset tremor disorders. Clinical and pathological studies suggest that misdiagnosis of PD for ET, and vice versa, occur in anywhere from 15% to 35% of cases. Complex diagnostic procedures, such as dopamine transporter imaging, can be powerful diagnostic aids but are lengthy and expensive procedures that are not widely available. Preliminary studies suggest that monitoring of tremor characteristics with consumer grade accelerometer devices could be a more accessible approach to the discrimination of PD from ET, but these studies have been performed in well-controlled clinical settings requiring multiple maneuvers and oversight from clinical or research staff, and thus may not be representative of at-home monitoring in the community setting. Therefore, we set out to determine whether discrimination of PD vs. ET diagnosis could be achieved by monitoring research subject movements at home using consumer grade devices, and whether discrimination could be improved with the addition of genetic profiling of the type that is readily available through direct-to-consumer genetic testing services. Forty subjects with PD and 27 patients with ET were genetically profiled and had their movements characterized three-times a day for two weeks through a simple procedure meant to induce rest tremors. We found that tremor characteristics could be used to predict diagnosis status (sensitivity = 76%, specificity = 65%, area under the curve (AUC) = 0.75), but that the addition of genetic risk information, via a PD polygenic risk score, did not improve discriminatory power (sensitivity = 80%, specificity = 65%, AUC = 0.73).
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Project description:Surprisingly little has been written about the combined clinical entity, essential tremor-Parkinson's disease (ET-PD), which is the result of a double disease hit. We carefully quantified tremor burden using a wide range of measures (tremor severity, tremor-related disability, tremor-related quality of life) and furthermore, studied additional motor and non-motor features in ET-PD.In this prospective, clinical-epidemiological study, we performed a standardized, structured clinical evaluation of 27 ET-PD patients, comparing them to age-matched samples of 35 PD and 109 ET patients.The number of hours/day shaking was lowest in PD (median=3.0), intermediate in ET (median=10.0) and highest in ET-PD (median=14.0) (p<0.001). All measures of mobility and balance (Berg Balance test, Activities-specific Balance Confidence Scale, Timed Up and Go test) worsened across groups in a stepwise manner from ET to PD to ET-PD (p<0.05). Mini-mental state test scores worsened (p=0.002) and daytime sleepiness increased (p=0.002) across groups from ET to PD to ET-PD.The ET-PD patient seems to be more than just a PD patient with a little more kinetic tremor. Aside from a significantly greater tremor burden, ET-PD patients exhibited more cognitive and sleep problems and more mobility and balance problems than patients with isolated PD.
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Project description:BackgroundEssential tremor (ET) and Parkinson's disease (PD) are common movement disorders. ET-PD syndrome is characterized by the occurrence of PD in patients with a previous history of ET, which may be an independent phenotype distinct from PD. This study aims to identify clinical characteristics and subtypes in ET-PD.MethodsA total of 93 newly diagnosed ET-PD patients and 93 newly diagnosed PD patients matched for age, sex, education, and disease duration of PD were selected using propensity score matching analysis. The K-means cluster analysis was performed for 11 variables derived from the ET-PD group, and cluster profiles were established through statistical analysis of demographic and clinical variables.ResultsThe ET-PD group consisted of a high number of patients with a family history of ET exhibiting evident tremor with milder hypokinesia and postural instability symptoms, as compared to the PD group. Through the cluster analysis, two clusters of ET-PD patients were identified. The ET-PD cluster 1 ( n = 34) had a shorter ET duration before PD onset, lower number of patients with a family history of ET, higher unified PD rating scale instability scores, higher non-motor symptoms scores (non-motor symptoms scale D1 scores, Hamilton depression scale scores, Hamilton anxiety scale scores, and PD sleep scale-2 scores), and higher Chinese version of the PD questionnaire-39 scores relative to the ET-PD cluster 2 ( n = 59).ConclusionET-PD patients had significantly different characteristics for motor symptoms as compared to PD patients, and may be distinctly divided into two clinical subtypes, namely, the ET-PD complex type and the ET-PD simple type.
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Project description:Epidemiological studies have reported a link between essential tremor (ET) and Parkinson's disease (PD). Recent studies have suggested ET as a possible neurodegenerative disease whose subgroup contained Lewy bodies in the brainstem, as in PD. PD with antedated ET (PDconv) might exhibit traits different from those of the pure form of ET or PD. This study aimed to unveil the interplay between PD and premorbid ET, which might be the core pathobiology that differentiates PDconv from PD. The study included 51 ET, 32 PDconv, and 95 PD patients who underwent positron emission tomography using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and 123I-meta-iodobenzylguanidine myocardial scintigraphy to analyze central dopaminergic and peripheral noradrenergic integrity. The results show that PDconv group followed the typical striatal pathology of PD but with a delay in noradrenergic impairment as it caught up with the denervating status of PD a few years after PD diagnosis. Whereas the two PD subtypes displayed similar patterns of presynaptic dopamine transporter deficits, ET patients maintained high densities in all subregions except thalamus. Presynaptic dopaminergic availability decreased in a linear or quadratic fashion across the three groups (ET vs. PDconv vs. PD). The age at onset and duration of ET did not differ between pure ET and PDconv patients and did not influence the striatal monoamine status. The myocardium in PDconv patients was initially less denervated than in PD patients, but it degenerated more rapidly. These findings suggest that PDconv could be a distinctive subclass in which the pathobiology of PD interacts with that of ET in the early phase of the disease.
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Project description:BackgroundSpiral drawing on papers is a common tremor evaluation tool for diagnosing patients with essential tremor (ET) or Parkinson's disease (PD). No standard drawing methods and parameters that use graphic tablets are yet available for objective evaluation.MethodsThis study established a tremor assessment system for tremor severity by using graphic tablets. Twelve patients with ET and twelve patients with PD were tested to establish system algorithms, and six additional patients were tested with the developed system to evaluate its performance. The patients also performed spiral drawing with three guiding paradigms on a graphic tablet: traced along a given spiral (S1), performed freehand drawing (S2), and traced along a guiding point (S3). Three parameters were calculated to quantify tremor severity: the means of radial difference per radian (|dr/dθ|), the means of radial difference per second (|dr/dt|), and the area under curve (AUC) of the frequency spectrum of the velocity. Each patient's drawing was also evaluated using a visual rating scale (VRS) by experienced physicians. The interrater reliability was examined to identify the most consistent test paradigm.ResultsThe parameter |dr/dθ| and AUC correlated well with the VRS (R > 0.8) in S1, S2 and S3 tests. The S1 test presented the best interrater reliability (Weighted Kappa coefficient, k = 0.80) among three tests. The Weighted Kappa coefficients are 0.67 and 0.71 in S2 and S3 tests, respectively.ConclusionsWe developed three different guiding paradigms for spiral drawing on a digital graphic tablet for clinical tests. Three parameters were calculated to represent the tremor severity in spiral drawing and used to quantify temporal and spatial characteristics of tremor, and provided good correlation with current clinical assessments. The test "traced along a given spiral" is recommended due to its good interrater reliability.
| S-EPMC5845296 | biostudies-literature