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BACKGROUND: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18F-9-fluoropropyldihydrotetrabenazine (18F-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). OBJECTIVE: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using 18F-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. METHODS: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using 18F-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. RESULTS: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. CONCLUSIONS: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. © 2024 International Parkinson and Movement Disorder Society.
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Corpo Estriado , Doença de Parkinson , Paralisia Supranuclear Progressiva , Proteínas Vesiculares de Transporte de Monoamina , Humanos , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Paralisia Supranuclear Progressiva/metabolismo , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Corpo Estriado/metabolismo , Corpo Estriado/diagnóstico por imagem , Doença de Parkinson/metabolismo , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tetrabenazina/análogos & derivados , Substância Negra/diagnóstico por imagem , Substância Negra/metabolismo , Substância Negra/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodosRESUMO
Brodifacoum exerts its antagonistic effect against the metabolism of vitamin K, an essential component in the synthesis of blood coagulation factors. This effect ultimately hinders the blood's capacity to clot effectively, rendering it a commonly employed rodenticide. Instances of lethal poisonings are exceedingly rare owing to expeditious medical intervention and treatment. Within this report, we present a case of brodifacoum-induced homicide, wherein the patient exhibited distinct clinical examinations and symptoms. Moreover, the patient's blood sample exhibited a noteworthy brodifacoum concentration of 0.681 µg/mL even after a period of 43 days following the incident of poisoning. Although an autopsy was not conducted due to religious restrictions, we endeavor to reasonably deduce the cause of death and furnish corroborative evidence for clinical diagnosis, treatment, and forensic examination in instances involving brodifacoum poisoning.
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Homicídio , Rodenticidas , Humanos , Rodenticidas/intoxicação , Masculino , Cromatografia Líquida , Espectrometria de Massas em Tandem , Toxicologia Forense , 4-Hidroxicumarinas/intoxicação , Adulto , Espectrometria de Massa com Cromatografia LíquidaRESUMO
BACKGROUND: Recent animal model studies have suggested that the parafascicular nucleus has the potential to be an effective deep brain stimulation target for Parkinson's disease. However, our knowledge on the role of the parafascicular nucleus in Parkinson's disease patients remains limited. OBJECTIVE: We aimed to investigate the functional alterations of the parafascicular nucleus projections in Parkinson's disease patients. METHODS: We enrolled 72 Parkinson's disease patients and 60 healthy controls, then utilized resting-state functional MRI and spectral dynamic causal modeling to explore the effective connectivity of the bilateral parafascicular nucleus to the dorsal putamen, nucleus accumbens, and subthalamic nucleus. The associations between the effective connectivity of the parafascicular nucleus projections and clinical features were measured with Pearson partial correlations. RESULTS: Compared with controls, the effective connectivity from the parafascicular nucleus to dorsal putamen was significantly increased, while the connectivity to the nucleus accumbens and subthalamic nucleus was significantly reduced in Parkinson's disease patients. There was a significantly positive correlation between the connectivity of parafascicular nucleus-dorsal putamen projection and motor deficits. The connectivity from the parafascicular nucleus to the subthalamic nucleus was negatively correlated with motor deficits and apathy, while the connectivity from the parafascicular nucleus to the nucleus accumbens was negatively associated with depression. CONCLUSION: The present study demonstrates that the parafascicular nucleus-related projections are damaged and associated with clinical symptoms of Parkinson's disease. Our findings provide new insights into the impaired basal ganglia-thalamocortical circuits and give support for the parafascicular nucleus as a potential effective neuromodulating target of the disease.
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Núcleos Intralaminares do Tálamo , Doença de Parkinson , Núcleo Subtalâmico , Animais , Humanos , Doença de Parkinson/diagnóstico por imagem , Putamen , Gânglios da Base , Núcleo Subtalâmico/diagnóstico por imagemRESUMO
Dimethyl sulfate (DMS) is a highly toxic chemical that appears innocuous and is commonly used as a methylating agent in industry. It can be readily absorbed leading to poisoning or death through the skin or mucous membranes of the respiratory tract in the process of production or transportation. Although there are some articles on treatment for DMS poisoning, reports of death resulting from acute fatal DMS poisoning are very rare. Here, we present a case of a 50-year-old Chinese man who died accidentally from DMS poisoning after he broke a plastic storage tank full of DMS during transportation. The patient complained of eye irritation. In addition, the corrosive damage could be seen in his corneas and skin. The autopsy revealed erosions and ulcers in the respiratory tract, as well as massive congestion, necrosis, edema, and pseudomembrane formation on the mucous layer of the trachea and main bronchi. Histopathological examination confirmed extensive pulmonary edema, multifocal hemorrhages, whole-cell swelling in the brain, as well as disintegration of the neuronal cell. We inferred that DMS poisoning caused the symptoms resulting from the production of methanol and sulfate through hydrolysis, including respiratory toxicity and neurotoxicity, and these symptoms had temporal continuity. Toxicological analysis revealed no DMS or methanol, but formic acid was detected in the brain, both qualitatively and quantitatively. In this report, we also present a retrospective study of 8 similar cases of DMS poisoning in literature in China, including some clinical data and autopsy information.
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A long-standing mystery shrouds the mechanism by which catalytically repressed receptor tyrosine kinase domains accomplish transphosphorylation of activation loop (A-loop) tyrosines. Here we show that this reaction proceeds via an asymmetric complex that is thermodynamically disadvantaged because of an electrostatic repulsion between enzyme and substrate kinases. Under physiological conditions, the energetic gain resulting from ligand-induced dimerization of extracellular domains overcomes this opposing clash, stabilizing the A-loop-transphosphorylating dimer. A unique pathogenic fibroblast growth factor receptor gain-of-function mutation promotes formation of the complex responsible for phosphorylation of A-loop tyrosines by eliminating this repulsive force. We show that asymmetric complex formation induces a more phosphorylatable A-loop conformation in the substrate kinase, which in turn promotes the active state of the enzyme kinase. This explains how quantitative differences in the stability of ligand-induced extracellular dimerization promotes formation of the intracellular A-loop-transphosphorylating asymmetric complex to varying extents, thereby modulating intracellular kinase activity and signaling intensity.
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Domínio AAA/fisiologia , Proteínas Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Domínio AAA/genética , Domínio Catalítico , Dimerização , Ativação Enzimática , Humanos , Ligantes , Fosforilação , Ligação Proteica , Conformação Proteica , Proteínas Tirosina Quinases/fisiologia , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/fisiologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Relação Estrutura-Atividade , Tirosina/químicaRESUMO
The citrate-based tissue adhesive, synthesized by citric acid, diol, and dopamine, is a kind of mussel-inspired adhesive. The adhesion of mussel-inspired adhesive is not completely dependent on 3, 4-dihydroxyphenylalanine (Dopa) groups. The backbone structure of the adhesive also greatly affects the adhesion. In this study, to explore the effects of hydrophobicity and hydrophilicity of the backbone structure on adhesion, we prepared a series of citrate-based tissue adhesives (POEC-d) by changing the molar ratio of two diols, 1, 8-octanediol (O) and poly(ethylene oxide) (E), which formed hydrophobic segment units and hydrophilic segment units, respectively, in the molecule structure. The properties of cured adhesives showed that the adhesive with high E units had high swelling, rapid degradation, and low cohesion. In the adhesion strength measurement on the porcine skin, the adhesive with higher hydrophobicity was more likely to perform better. For the interfacial adhesion, hydrophilicity was conducive to the diffusion and penetration on the skin surface, but hydrophobic interaction showed a stronger effect to adhere with skin and hydrophobic association increased the adhesive concentration on the interface; for the bulk cohesion, hydrophobicity led to coacervation, promoting the Dopa-quinone coupling for cross-linking. In this amphipathic, citrate-based, soft-tissue adhesive system, when the feed ratio of hydrophilic segment was lower than 0.7, the coacervation could be formed through hydrophobic interaction, forming an efficient underwater adhesion system similar to that of mussels.
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BACKGROUND: Lower urinary tract symptoms are one of the most common groups of non-movement symptoms in patients with Parkinson's disease (PD). Storage symptoms are well-acknowledged, but neurogenic voiding dysfunction caused by PD remains a knowledge gap. This study aimed to evaluate the neurogenic bladder outlet obstruction in male patients with PD and its clinical significance. METHODS: Male patients who were diagnosed with PD and underwent urodynamic studies were retrospectively reviewed. The patients with prostate size < 30 ml and bladder outlet obstruction index ≥40 were included in the study. Lower urinary tract symptoms were evaluated by International Prostate Symptom Score (IPSS). Free flowmetry was performed and post void residual (PVR) volume was measured by ultrasound at follow-up. RESULTS: Six patients were included in the final analysis. The mean age was 68.2 and the mean movement symptom duration was 70.7 months. The patients had a mean IPSS of 12.5 and mean PVR volume of 70.8 ml. All patients had slow stream but none of them reported significant voiding difficulty. Urodynamic studies showed the delayed urinary sphincter relaxation and the special trace pattern. After a mean follow-up of 20 months, they had a mean IPSS of 12.5 and mean PVR volume of 73.3 ml. None of them complained of significant voiding difficulty at follow-up. CONCLUSION: The delayed urinary sphincter relaxation is a rare but repeatable phenomenon in male patients with PD. It is unlikely to cause disturbing voiding dysfunction, as reported by the patients, and does not progress prominently during the course of PD. Further studies are needed to investigate the nature of this special type of neurogenic BOO and whether it is peculiar to PD in a larger patient cohort.
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Sintomas do Trato Urinário Inferior/etiologia , Doença de Parkinson/complicações , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Idoso , Estudos de Coortes , Humanos , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , UrodinâmicaRESUMO
BACKGROUND: Emerging evidence indicates that inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Several proteins including α-synuclein trigger the activation of NLRP3 inflammasome. However, few studies examined whether inflammasomes are activated in the periphery of PD patients and their possible value in the diagnosis or tracking of the progress of PD. The aim of this study was to determine the association between inflammasome-induced inflammation and clinical features in PD. METHODS: There were a total of 67 participants, including 43 patients with PD and 24 controls, in the study. Participants received a complete evaluation of motor and non-motor symptoms, including Hoehn and Yahr (H-Y) staging scale. Blood samples were collected from all participants. The protein and mRNA expression levels of inflammasomes subtypes and components in peripheral blood mononuclear cells (PBMCs) were determined using western blotting and RT-qPCR. We applied Meso Scale Discovery (MSD) immunoassay to measure the plasma levels of IL-1ß and α-synuclein. RESULTS: We observed increased gene expression of NLRP3, ASC, and caspase-1 in PBMCs, and increased protein levels of NLRP3, caspase-1, and IL-1ß in PD patients. Plasma levels of IL-1ß were significantly higher in patients with PD compared with controls and have a positive correlation with H-Y stage and UPDRS part III scores. Furthermore, plasma α-synuclein levels were also increased in PD patients and have a positive correlation with both UPDRS part III scores and plasma IL-1ß levels. CONCLUSIONS: Our data demonstrated that the NLRP3 inflammasome is activated in the PBMCs from PD patients. The related inflammatory cytokine IL-1ß and total α-synuclein in plasma were increased in PD patients than controls, and both of them presented a positive correlation with motor severity in patients with PD. Furthermore, plasma α-synuclein levels have a positive correlation with IL-1ß levels in PD patients. All these findings suggested that the NLRP3 inflammasome activation-related cytokine IL-1ß and α-synuclein could serve as non-invasive biomarkers to monitor the severity and progression of PD in regard to motor function.
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Progressão da Doença , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Índice de Gravidade de Doença , alfa-Sinucleína/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
During the 1990s, we estimated the genetic contribution to Parkinson's disease risk in a large, population-based twin registry. Because many unaffected twins were still alive, previous concordance estimates were based on incomplete information. Ninety-five percent of twins are now deceased. Here, we update concordance and heritability through 2015 using National Death Index data. In total, we identified 30 concordant and 193 discordant pairs. Proband-wise concordance was 0.20 in monozygotic and 0.13 in dizygotic pairs. Heritability was 0.27 overall, 0.83 in pairs diagnosed ≤50, and 0.19 in pairs diagnosed >50. High concordance in dizygotic twins suggests shared effects of early childhood environment. Ann Neurol 2019;85:600-605.
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Doenças em Gêmeos/genética , Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças em Gêmeos/epidemiologia , Feminino , Seguimentos , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder is an early sign of neurodegenerative disease. This study aimed to quantitatively evaluate iron content in idiopathic rapid eye movement sleep behavior disorder patients using quantitative susceptibility mapping and to examine the potential of this technique to identify the prodromal stage of α-synucleinopathies. METHODS: Twenty-five idiopathic rapid eye movement sleep behavior disorder patients, 32 Parkinson's disease patients, and 50 healthy controls underwent quantitative susceptibility mapping. The mean magnetic susceptibility values within the bilateral substantia nigra, globus pallidus, red nucleus, head of the caudate nucleus, and putamen were calculated and compared among groups. The relationships between the values and the clinical features of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease were measured using correlation analysis. RESULTS: Idiopathic rapid eye movement sleep behavior disorder patients had elevated iron in the bilateral substantia nigra compared with healthy controls. Parkinson's disease patients had increased iron in the bilateral substantia nigra, globus pallidus, and left red nucleus compared with healthy controls and had elevated iron levels in the bilateral substantia nigra compared with idiopathic rapid eye movement sleep behavior disorder patients. Mean magnetic susceptibility values were positively correlated with disease duration in the left substantia nigra in idiopathic rapid eye movement sleep behavior disorder patients. CONCLUSIONS: Quantitative susceptibility mapping can detect increased iron in the substantia nigra in idiopathic rapid eye movement sleep behavior disorder, which becomes more significant as the disorder progresses. This technique has the potential to be an early objective neuroimaging marker for detecting α-synucleinopathies. © 2019 International Parkinson and Movement Disorder Society.
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Doenças Neurodegenerativas , Transtorno do Comportamento do Sono REM , Globo Pálido , Humanos , Ferro , Substância NegraRESUMO
Polyvinylpyrrolidone (PVP) nanofilms prepared by spin-coating have vast applications in biological and microdevice fields. However, detailed knowledge of processing induced nonequilibrium behavior of PVP nanofilms and solutions for minimizing residual stresses toward high-quality films has still been lacking. In the present study, we first explored the rapid film formation process via statistics on nascent holes. Next, by employing dewetting as a major probe, we revealed that many processing conditions, particularly previously overlooked variables like the atmosphere, substrates, and immersion time, were correlated substantially with the degree of nonequilibrium of nanofilms. Proper aging temperature and time were demonstrated essential for releasing residual stresses and achieving more equilibrium nanofilms. This work offered abundant experimental evidence in the building relationship between the processing and nonequilibrium nature of polymer nanofilms, which were crucial for their preparation and application.
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PURPOSE: To evaluate whether neurogenic lower urinary tract dysfunction and urodynamic parameters predict the outcomes of patients with multiple system atrophy (MSA). METHODS: A retrospective study was performed in patients who were diagnosed with MSA and underwent urodynamic studies simultaneously from September 2014 to July 2018. The urodynamic traces were reviewed by urologists. Detrusor contractility was evaluated by the bladder contractility index (BCI) and Schäfer nomogram. Telephone follow-up was conducted in July 2019 to acquire survival data. Clinical and urodynamic parameters were analyzed for survival using Cox regression analysis. RESULTS: Overall, 70 MSA patients were eligible for analysis, and 61 of them underwent urodynamic study within 3 years of initial symptom onset. The parkinsonian subtype of MSA (MSA-P) had a smaller proportion of men as well as longer motor and lower urinary tract symptom durations than the cerebellar subtype (MSA-C). MSA-P also had a lower mean BCI than MSA-C (32.0 ± 27.0 versus 53.6 ± 33.4, p = 0.025). The mean MSA survival time was 5.4 [95% confidence interval (CI) 4.8-6.3] years. Cox regression analysis showed that survival from baseline was correlated only with BCI [hazard ratio (HR) 0.983, 95% CI 0.969-0.997, p = 0.020]. Overall survival was correlated with BCI (HR 0.982, 95% CI 0.966-0.999, p = 0.039) and the presence of urinary incontinence (HR 3.007, 95% CI 0.993-9.220, p = 0.052). CONCLUSION: Detrusor contractility can be a prognostic marker in MSA patients. A high BCI value is a protective factor for survival from baseline and overall survival. The presence of urinary incontinence predicts shortened overall survival.
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Atrofia de Múltiplos Sistemas , Humanos , Masculino , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/diagnóstico , Prognóstico , Estudos Retrospectivos , Bexiga Urinária , UrodinâmicaRESUMO
Determining the locations and distributions of Al substitution in zeolite-based catalysts and catalysis is always very challenging. Despite advanced experimental characterization techniques and improved theoretical models, this issue is not reasonably solved and this is because the locations and distributions of Al substitution in zeolites are more kinetically than thermodynamically controlled. In this work, we computed one Al substitution in the orthorhombic form of MFI (HZSM-5) which contains 12 distinct tetrahedral (T) centers on the basis of a periodic slab model containing 96 T centers including van der Waals dispersion correction (GGA-PBE-D3). For all 12 T centers, there are 48 acidic sites and each site can be considered for the adsorption of probe molecules. Thermodynamically, the energy span of the twelve most stable acidic sites is less than 15 kJ mol-1, and such a small energy difference enables all adjustable possibilities for the locations and distributions of Al substitution under suitable conditions. Excellent agreement between experiment and theory in the adsorption enthalpies of pyridine, methylamine, dimethylamine and trimethylamine shows that the location of Al substitution is most likely at T1, T3, T5, T7 and T11, while much less likely at the often used T12 site. These results provide the basis for identifying Al substitution in new synthesized HZSM-5 catalysts and for studying the acidic site-dependent catalytic activity of HZSM-5 in cracking and hydrogenation reactions.
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AIMS: To confirm whether the presence and/or timing of rapid eye movement sleep behavior disorder (RBD) onset were associated with differences in clinical features of Parkinson's disease (PD), clinical characteristics of PD patients with RBD occurring before and after PD diagnosis were investigated. METHODS: Consecutive PD patients were enrolled between July 2011 and February 2012. RBD questionnaire Hong Kong and clinical interviews were used to identify RBD symptoms and onsets. All patients underwent evaluations to collect clinical and treatment information. RESULTS: Of all 79 PD patients, 21 (26.6%) and 22 (27.8%) patients had RBD prior to (RBD-PD) and after PD diagnosis (PD-RBD), respectively. Thirty-six (45.6%) PD patients reported no RBD at the time of study (PD-NRBD). PD-RBD had similar clinical features as PD-NRBD did except that Epworth sleepiness scale score was significantly higher in PD-RBD (p = 0.04). Compared to PD-RBD and PD-NRBD, RBD-PD had a higher frequency of reporting excessive daytime sleepiness (p = 0.019, p = 0.008, respectively) and constipation (p = 0.046, p = 0.032, respectively). CONCLUSION: Our preliminary results suggest that RBD-PD might be clinically different from PD-RBD, which appears to share similar characteristics with PD-NRBD, regarding only non-motor functions.
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Doença de Parkinson/diagnóstico , Transtorno do Comportamento do Sono REM/diagnóstico , Idoso , Testes de Percepção de Cores , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Transtornos do Olfato/diagnóstico , Polissonografia , Estatística como Assunto , Inquéritos e QuestionáriosRESUMO
Non-motor symptoms (NMS) are common among patients with Parkinson's disease (PD). However, reports on NMS in Chinese PD population are scarce. Little is known about NMS in patients with Asian specific leucine-rich repeat kinase 2 (LRRK2) variants in G2385R and R1628P. This study aimed to elucidate the clinical characteristics of NMS in Chinese PD patients and to ascertain if there were differences in NMS between PD patients with and without LRRK2 variants. A multicenter, observational study was conducted with 1,225 sporadic PD (sPD) patients recruited from a PD cohort of the Chinese National Consortium on neurodegenerative diseases, 163 participants had the LRRK2 variants. The Non-motor Symptom Questionnaire (NMSQ) was used to screen for the presence of NMS. This study found the majority of sPD patients (97.6 %) had at least one NMS. A mean of 8.72 NMS (SD = 5.43) was reported per patient. Forgetfulness, constipation and daytime sleepiness were found to be the most frequent NMS. Moreover, the number of NMS was positively correlated with the age, disease duration, Hoehn & Yahr stage and the motor scores of the unified Parkinson's disease rating scale. Although no discrepancy was found in the number of NMS between sPD patients with and without LRRK2 variants, nocturia was less common in LRRK2 variants carriers than in non-carriers (P = 0.045). NMS appear to be prevalent in Chinese sPD population. There are no differences in the NMS phenotype between LRRK2 and no LRRK2 patients.
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Variação Genética , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Fatores Etários , Antiparasitários/uso terapêutico , Povo Asiático/genética , China , Estudos de Coortes , Feminino , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de TempoRESUMO
Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 µg/ml in heart blood, 39 µg/ml in femoral vein blood, 141 µg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning.
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Antieméticos/intoxicação , Piperidinas/intoxicação , Antieméticos/análise , Antieméticos/química , Edema Encefálico/patologia , Feminino , Conteúdo Gastrointestinal/química , Humanos , Fígado/química , Estrutura Molecular , Piperidinas/análise , Piperidinas/química , Estudos Retrospectivos , Suicídio , Adulto JovemRESUMO
PURPOSE: Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. METHOD: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences. FINDING: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD. CONCLUSION: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD.
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Memória de Curto Prazo , Doença de Parkinson , Paralisia Supranuclear Progressiva , Humanos , Paralisia Supranuclear Progressiva/fisiopatologia , Paralisia Supranuclear Progressiva/tratamento farmacológico , Masculino , Feminino , Idoso , Doença de Parkinson/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Pessoa de Meia-Idade , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Levodopa/administração & dosagem , Levodopa/farmacologia , Levodopa/uso terapêuticoRESUMO
INTRODUCTION: Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP. METHODS: Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity. RESULTS: The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words. CONCLUSIONS: These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS.
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Levodopa , Doença de Parkinson , Semântica , Paralisia Supranuclear Progressiva , Humanos , Paralisia Supranuclear Progressiva/tratamento farmacológico , Paralisia Supranuclear Progressiva/fisiopatologia , Masculino , Feminino , Idoso , Levodopa/administração & dosagem , Levodopa/farmacologia , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/farmacologiaRESUMO
BACKGROUND: Vibrotactile stimulation has been studied in its efficacy of reducing freezing of gait (FOG) in patients with Parkinson's disease (PD). However, the results are still controversial. We evaluated the efficacy of a newly developed vibrotactile foot device on freezing severity and gait measures in PD patients with FOG. OBJECTIVE: To evaluate the efficacy of vibrotactile foot device on PD patients with FOG. METHODS: Thirty-three PD patients with FOG were examined during their "off" medication state. The efficacy of the vibrotactile foot device was evaluated using a gait protocol comprising walking trials with vibrotactile stimulation "off" and "on." Walking trials were videotaped for the offline rating by two movement disorder specialists. The Opal inertial sensor unit (128 Hz; Mobility Lab; APDM Inc., Portland, OR, USA) was used for quantitative gait analysis. RESULTS: The results demonstrated 33.1% reduction in number of FOG episodes (P < 0.001) and 32.6% reduction of freezing episodes (P < 0.001). Quantitative gait analysis showed a significant increase in step length (P = 0.033). A moderate negative correlation was observed between the change of percent time frozen and age (r = -0.415, P = 0.016). 73% of participants reported minimal to substantial improvement in walking with this vibrating stimulation delivered by the vibrotactile foot device. CONCLUSIONS: The vibrotactile foot device is an efficient device that could significantly reduce freezing severity and provide gait regulation to patients with PD experiencing frequent freezing. It could potentially be used in the home environment for improving the quality of life.