RESUMO
Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.
Assuntos
Melanoma , Doença de Parkinson , Neoplasias Cutâneas , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Melanoma/complicações , Melanoma/epidemiologia , Melanoma/genética , Bases de Dados Factuais , Melanoma Maligno CutâneoRESUMO
BACKGROUND: The p.A53T point mutation in the α-synuclein gene (SNCA) is a rare but highly relevant cause of autosomal dominant Parkinson's disease (PD). OBJECTIVES: The objective of this study was to assess striatal dopaminergic denervation in a cohort of symptomatic carriers of the p.A53T SNCA mutation as compared to PD patients. METHODS: Data from the Parkinson's Progression Markers Initiative database of 11 symptomatic p.A53T SNCA mutation carriers who underwent 123I-FP-CIT SPECT [(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging at our site were compared with those of 33 age-, sex-, and disease duration-matched PD patients. RESULTS: The p.A53T mutation carriers had significantly lower caudate nucleus binding ratio both contralaterally and ipsilaterally to the most affected side (P = .002 and P = .006) and a decreased contralateral caudate/putamen signal ratio (P = .007) as compared to PD. A similar degree of striatal asymmetry was observed in both subgroups. No correlation between scores in neuropsychological tests and caudate nucleus dopaminergic denervation could be demonstrated. CONCLUSIONS: PD patients harboring the p.A53T SNCA mutation show evidence of a more severe nigrostriatal denervation, especially evident in the caudate nucleus. The lack of significant differences in the putaminal binding ratios may reflect a floor effect or a true preferential targeting of the caudate terminals in p.A53T SNCA-associated PD. © 2018 International Parkinson and Movement Disorder Society.
Assuntos
Mutação/genética , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , alfa-Sinucleína/genética , Adulto , Alanina/genética , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Estudos de Coortes , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Treonina/genética , Tropanos/farmacocinéticaRESUMO
BACKGROUND: The role of blood uric acid as a biomarker in symptomatic motor PD has been increasingly established in the literature. OBJECTIVE: Our present study assessed the role of serum uric acid as a putative biomarker in a prodromal PD cohort [REM Sleep Behavior disorder (RBD) and Hyposmia] followed longitudinally. METHODS: Longitudinal 5-year serum uric acid measurement data of 39 RBD patients and 26 Hyposmia patients with an abnormal DATSCAN imaging were downloaded from the Parkinson's Progression Markers Initiative database. These cohorts were compared with 423 de novo PD patients and 196 healthy controls enrolled in the same study. RESULTS: After adjusting for age, sex, body mass index, and concomitant disorders (hypertension/gout), baseline and longitudinal serum uric acid levels were higher in the RBD subgroup as compared to the established PD cohort (pâ=â0.004 and pâ=â0.001). (Baseline RBD 6.07±1.6 vs. Baseline PD 5.35±1.3âmg/dL and Year-5 RBD 5.7±1.3 vs. Year-5 PD 5.26±1.33). This was also true for longitudinal measurements in the Hyposmic subgroup (pâ=â0.008) (Baseline Hyposmic 5.7±1.6 vs. PD 5.35±1.3âmg/dL and Year-5 Hyposmic 5.58±1.6 vs. PD 5.26±1.33). CONCLUSION: Our results indicate that serum uric acid levels are higher in prodromal PD subjects with ongoing dopaminergic degeneration compared to those with manifest PD. These data indicate that the well-established decrease in the levels of serum uric acid occurs with the transition from prodromal to clinical PD. Whether the higher levels of serum uric acid observed in prodromal PD may provide protection against conversion to full-blown clinical PD will require further study.
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Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Ácido Úrico , Anosmia , Transtorno do Comportamento do Sono REM/etiologia , Transtorno do Comportamento do Sono REM/complicações , Biomarcadores , Sintomas ProdrômicosRESUMO
INTRODUCTION: Higher prevalence of motor and non-motor features has been observed in non-manifesting mutation carriers of Parkinson's Disease (PD) compared to Healthy Controls (HC). The aim was to detect the differences between GBA and LRRK2 mutation carriers without PD and HC on neuropsychiatric symptoms. METHODS: This is a cross-sectional retrospective study of non-manifesting GBA and LRRK2 mutation carriers and HC enrolled into Parkinson's Progression Markers Initiative (PPMI). Data extracted from the PPMI database contained: demographics and performance in MoCA scale and MDS-UPDRS scale part 1A (neuropsychiatric symptoms). All six features were treated as both continuous (MDS-UPDRS individual scores) and categorical variables (MDS-UPDRS individual score>0 and MDS-UPDRS individual score = 0). Logistic regression analyses were applied to evaluate the association between mutation carrying status and neuropsychiatric symptoms. RESULTS: In this study, the neuropsychiatric evaluation was performed in 285 GBA non-manifesting carriers, 369 LRRK2 non-manifesting carriers and 195 HC. We found that GBA non-manifesting mutation carriers were 2.6 times more likely to present apathy compared to HC, even after adjustment for covariates (adjusted OR = 2.6, 95% CI = 1.1-6.3, p = 0.031). The higher percentage of apathy for LRRK2 carriers compared to HC was marginally non-significant. GBA carriers were 1.5 times more likely to develop features of anxiety compared to LRRK2 carriers (adjusted OR = 1.5, 95% CI = 1.1-2.2, p = 0.015). Other neuropsychiatric symptoms, such as psychotic or depressive manifestations, did not differ between groups. CONCLUSION: Symptoms of apathy could be present in the prediagnostic period of non-manifesting mutation carriers, especially, GBA. Longitudinal data, including detailed neuropsychiatric evaluation and neuroimaging, would be essential to further investigate the pathophysiological basis of this finding.
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Apatia , Glucosilceramidase/genética , Heterozigoto , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Doença de Parkinson/genética , Idoso , Estudos de Casos e Controles , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
BACKGROUND: Previous studies have highlighted serum uric acid as a putative idiopathic Parkinson's disease (iPD) biomarker. Only one study, so far, showed higher levels of serum uric acid in leucine-rich repeat kinase 2 (LRRKâ+â2) carriers compared to those who developed PD, however a longitudinal comparison between LRRK2â+âPD and healthy controls (HC) has not been performed. OBJECTIVE: The aim of this study was to determine whether there are longitudinal differences in serum uric acid between iPD, LRRK2â+âPD and HC and their association with motor and non-motor features. METHODS: Longitudinal data of uric acid of 282 de novo iPD, 144 LRRK2â+âPD patients, and 195 age-matched HC were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. We also used longitudinal Montreal Cognitive Assessment (MoCA), Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III), Geriatric Depression Scale (GDS) scores, and DaTSCAN striatal binding ratios (SBRs). RESULTS: Longitudinal uric acid measurements were significantly lower in LRRK2â+âPD patients compared to HC up to 5 years follow-up. There was no significant impact or correlation of adjusted or unadjusted uric acid levels with MoCA, MDS-UPDRS III, or GDS scores, the presence of RBD or DAT-SCAN SBRs. CONCLUSION: LRRK2â+âPD group had significantly lower uric acid concentrations compared to HC after adjusting for age, sex and baseline BMI up to 5 years follow-up. There were no significant associations between uric acid levels and indices of disease severity. These findings identify serum uric acid as a marker linked to LRRK2â+âPD.
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Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Doença de Parkinson , Ácido Úrico/química , Idoso , Biomarcadores , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/química , Mutação , Ácido Úrico/metabolismoRESUMO
INTRODUCTION: Blood uric acid represents an important biomarker in sporadic Parkinson's disease (PD). Whether uric acid levels change in genetic forms of PD is beginning to be assessed. The aim of the present study was to evaluate differences in serum uric acid level among PD patients harboring mutations in the glucocerebrosidase (GBA1) gene, sporadic PD, and healthy controls followed longitudinally. METHODS: Longitudinal 2-year serum uric acid measurement data of 120 GBA-PD patients have been downloaded from the Parkinson's Progression Markers Initiative (PPMI) database. This cohort was compared with 369 de novo sporadic PD patients and 195 healthy controls enrolled in the same study. RESULTS: Following adjustment for age, sex and BMI the GBA-PD cohort exhibited lower 2-year longitudinal uric acid level as compared to the controls (p = 0.016). Baseline uric acid measurements showed only a marginal difference (p = 0.119), but year 2 uric acid levels were lower in the GBA-PD cohort (p < 0.001). There was no difference in baseline, year 2 and 2-year longitudinal serum uric acid in the GBA-PD cohort as compared to sporadic PD (p = 0.664, p = 0.117 and p = 0.315). CONCLUSIONS: This is the first study to assess serum uric acid in a GBA-PD cohort. Our findings suggest that low serum uric acid might be a progression biomarker in GBA-PD. However, more studies (ideally longitudinal) on the association between low serum uric acid and clinical data in GBA-PD are needed. These results are consistent with data from previous reports assessing uric acid as a biomarker in other genetic forms of PD.
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Glucosilceramidase/genética , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Ácido Úrico/sangue , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Blood uric acid level represents an emerging biomarker in Parkinson's disease (PD). Whether uric acid levels change in genetic forms of PD is just beginning to be explored. OBJECTIVE: The aim of the present study was to assess differences in serum uric acid level among PD patients harboring the p.A53T mutation in the alpha-synuclein gene, idiopathic PD, and healthy controls. METHODS: Longitudinal 5-year serum uric acid measurement data of 369 de novo idiopathic PD patients and 174 age- and gender-matched healthy controls have been downloaded from the Parkinson's Progression Markers Initiative (PPMI) database. Furthermore, we assessed baseline serum uric acid measurements of 24 p.A53T alpha-synuclein PD patients enrolled in PPMI and followed in our site as compared to 24 age-, gender- and disease duration-matched sporadic PD patients and 24 healthy controls. RESULTS: Longitudinal serum uric acid measurements did not differ statistically between idiopathic PD patients and healthy controls (despite a trend for lower uric acid in the PD group) (pâ=â0.879). This was also true when male and female subgroups were assessed separately. The p.A53T SNCA mutation carrier PD group exhibited lower baseline serum uric acid level as compared to their matched healthy controls (pâ=â0.025). CONCLUSION: In the present study we did not replicate the established lower serum uric acid measurements in PD patients as compared to controls using PPMI data, possibly due to the fact that PD patients in baseline visit were de novo and the average disease duration was shorter than that observed in most epidemiological PD studies. The faster progression rate and increased disease severity in p.A53T PD possibly correlate with the lower serum uric acid observed in this subgroup.
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Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Ácido Úrico/sangue , alfa-Sinucleína/genética , Idoso , Biomarcadores/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: It has been reported that early onset Parkinson's Disease (PD) patients have a less profound dopaminergic degeneration. The aim of the current study was to determine whether there are longitudinal differences in dopaminergic denervation [signal reduction in 123I-FP-CIT SPECT] in early versus mid and late onset PD. METHODS: DaTSCAN (123I-FP-CIT SPECT) imaging was acquired at Parkinson's Progression Markers Initiative (PPMI) imaging centers and sent to the imaging core for calculation of striatal binding ratios. Data from the PPMI database of 58 early de novo PD patients (age ≤ 50 years) were compared to those of 362 mid and late onset PD patients (age > 50 years). RESULTS: Although raw striatal binding ratios were higher in early onset versus mid/late onset PD, especially on the ipsilateral side, such differences were not observed, and were in fact reversed in the contralateral putamen, after age correction. The rate of signal decline was similar between the two groups. Interestingly, based on both raw and age-adjusted data, caudate nucleus and putamen asymmetry (contralateral/ipsilateral ratio) was more pronounced in early onset PD. Striatal asymmetry also significantly correlated with age at onset as a continuous variable. CONCLUSION: Early onset PD patients exhibited similar rates of decline of dopaminergic denervation compared to mid/late onset PD. These results are not supportive of a more benign disease in this subgroup. The more pronounced asymmetry in early onset PD may however signify a qualitatively different pattern of neurodegeneration compared to mid/late onset PD.
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Núcleo Caudado/patologia , Progressão da Doença , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Diagnóstico Precoce , Doença de Parkinson/diagnóstico por imagem , Idoso , Núcleo Caudado/metabolismo , Dopamina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos/metabolismoRESUMO
Radiographers constitute an important part of a multidisciplinary radiation-based imaging and therapy chain. However, is there a common framework for assuring high education, training, and subsequent practice of profession among European countries? A study was conducted, based on a questionnaire that consisted of three parts, concerning education and training (Part A), national registry (Part B), and professional issues (Part C). Analysis of the collected data suggested that a common policy is generally followed in the countries investigated; however, differences were not negligible. A common framework of educational programmes among European countries could form the basis for overall standardisation at national and international level.