RESUMO
BACKGROUND: Vietnam-era veterans were exposed to Agent Orange (AO), which is associated with a high prevalence of Parkinson's disease (PD). However, little is known about the development of PD-like symptoms caused by drug-induced parkinsonism (DIP) in such populations. This study aimed to investigate PD incidence and PD risk following exposure to AO or DIP-risk drugs in veterans. METHODS: A retrospective cohort study was conducted using 12 years (2009-2020) of electronic medical records of the Veterans Health Service Medical Center, the largest Veterans Affairs hospital in South Korea (n = 37,246; 100% male; age, 65.57 ± 8.12 years). Exposure to AO or DIP-risk drugs, including antipsychotic, prokinetic, anti-epileptic, dopamine-depleting and anti-anginal agents, was assessed in veterans with PD, operationally defined as having a PD diagnosis and one or more prescriptions for PD treatment. The PD risk was calculated using multiple logistic regression analysis adjusted for age and comorbidities. RESULTS: The rates of DIP-risk drug use and AO exposure were 37.92% and 62.62%, respectively. The PD incidence from 2010 to 2020 was 3.08%; 1.30% with neither exposure, 1.63% with AO exposure, 4.38% with DIP-risk drug use, and 6.33% with both. Combined exposure to AO and DIP-risk drugs increased the PD risk (adjusted odds ratio = 1.68, 95% confidence interval, 1.36-2.08, P < 0.001). CONCLUSIONS: The PD incidence was 1.31 times higher with AO exposure alone and 1.68 times higher with AO exposure and DIP-risk drug use. The results suggest the necessity for careful monitoring and DIP-risk drug prescription in patients with AO exposure.
Assuntos
Doença de Parkinson Secundária , Doença de Parkinson , Veteranos , Humanos , Masculino , Idoso , Feminino , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Estudos Retrospectivos , Agente Laranja/efeitos adversos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnósticoRESUMO
INTRODUCTION: Reliable diagnosis of vascular parkinsonism (VaP) in the presence of a gait hypokinesia is an issue that is encountered in geriatrics. The EVAMAR-AGEX study was focusing on the phenomenon of recurrent falls in older persons (OP) with this parkinsonian gait. The present study is focusing on the diagnosis of VaP-related parkinsonian gait by developing a diagnostic guidance model adapted to OP. METHODS: Data from baseline and the 2-year follow-up visit were used to carry out univariate analysis and calculation of odds ratios, allowing to identify relevant variables to include in the diagnostic guidance model. To evaluate the model, confusion matrices were created, evaluating true positive, false negative, false positive and true negative incidences, sensitivity and specificity, and negative and positive predictive values. RESULTS: 79 patients included 58% male; average age 81.24 years. VaP diagnosis according to Zijlmans criteria occurred in 28%; neurodegenerative parkinsonian syndromes in 72%. A 4-criteria model was established to facilitate diagnostic: lack of prior hallucinations, lack of movement disorders tremor excluded, no cognitive fluctuations, and ≥75 years of age at diagnosis. In combination of 4/4 criteria, all of them were required to disclose a specificity of 91% in the diagnosis of VaP. In combination of 3/4, in case of negative test, a negative predictive value for VaP diagnosis of 0.97 was obtained. CONCLUSION: The challenge of our tool is both to be able to rule out what is probably not a VaP and to argue what makes a VaP diagnosis probable in OP.
Assuntos
Transtornos dos Movimentos , Doença de Parkinson Secundária , Transtornos Parkinsonianos , Doenças Vasculares , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Hipocinesia/diagnóstico , Hipocinesia/etiologia , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/diagnóstico , Tremor/epidemiologia , Marcha , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/etiologiaRESUMO
OBJECTIVE: The present study aimed to investigate levels and clinical significance of serum SIRT1 in Parkinson's disease (PD) and Vascular parkinsonism (VP). METHODS: This prospective observational research enrolled a total of 165 VP and 159 PD patients who were admitted during March 2018 to December 2021. Blood samples and medical characteristics were also obtained from 160 healthy volunteers. The serum Sirtuin1 (SIRT1) and cytokines levels of all subjects were measured by enzyme-linked immunosorbent assay (ELISA) method. Demographic and clinical data were also collected. Statistical analysis was conducted using SPSS software with P < 0.05 as statistically different. RESULTS: The mean age, the UPDRSIII score of VP patients was significantly higher compared with the PD patients (p<0.05), while the MMSE score of VP patients was significantly lower than the PD patients (p<0.001). The serum SIRT1 levels of the VP patients were remarkably lower than the PD patients or the healthy persons (p<0.05). Pearson's analysis showed that SIRT1 levels were negatively correlated with levels of IL-6, TNF- α and hcy. The UPDRSIII of SIRT1 low levels group was remarkably higher than the SIRT1 high levels group (p=0.048), while the MMSE score was lower than the SIRT1 high levels group (p<0.001). In addition, ROC curves showed that SIRT1 could be a potential diagnostic biomarker of VP. SIRT1 was a risk factor for VP. CONCLUSION: Our present study indicated that SIRT1 associated with disease severity and could discriminate PD from VP.
Assuntos
Doença de Parkinson Secundária , Doença de Parkinson , Doenças Vasculares , Humanos , Estudos Observacionais como Assunto , Doença de Parkinson/diagnóstico , Doença de Parkinson Secundária/diagnóstico , Estudos Prospectivos , Sirtuína 1RESUMO
Parkinson's disease is a neurodegenerative disorder while secondary-parkinsonism can be caused by infectious, inflammatory, traumatic, vascular, hereditary, paraneoplastic, or even induced by drug/metal poisoning. Here we report an uncommon subacute parkinsonism who presented with micrographia and mild cognitive impairment. The CSF examination showed inflammatory profile and positive anti-NMDAR antibody. The patient showed no improvement with levodopa/benserazide administration but satisfactory response to immunotherapy with methylprednisolone. This case indicated that autoimmune etiology should also be considered in parkinsonism to exclude a treatable condition.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Autoanticorpos/líquido cefalorraquidiano , Disfunção Cognitiva/etiologia , Escrita Manual , Imunoterapia , Doença de Parkinson Secundária/imunologia , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Antiparkinsonianos/uso terapêutico , Benserazida/uso terapêutico , Combinação de Medicamentos , Febre de Causa Desconhecida/etiologia , Humanos , Imunossupressores/uso terapêutico , Levodopa/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Testes Neuropsicológicos , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/tratamento farmacológico , Doença de Parkinson Secundária/psicologia , Tremor/etiologiaRESUMO
Phosphodiesterase 10A (PDE10A), the enzyme which catalyzes hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), is located almost exclusively in striatal γ-amino-butyric acid (GABA)ergic medium spiny neurons (MSNs). Since dopaminergic deficiency in Parkinson's disease (PD) leads to functional imbalance of striatal direct and indirect output pathways formed by MSNs, PDE10A seems to be of special interest as a potential therapeutic target in PD. The aim of the present study was to examine the influence of 7-{5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl}-2-phenylimidazo[1,2-a]pyrimidine (CPL500036), a novel selective inhibitor of PDE10A, on sensorimotor deficits and therapeutic effects of L-3,4-dihydroxyphenylalanine (L-DOPA) in hemiparkinsonian rats. Animals were unilaterally lesioned with 6-hydroxydopamine, and their sensorimotor deficits were examined in the stepping, cylinder, vibrissae and catalepsy tests. CPL500036 (0.1 and 0.3 mg/kg) was administered either acutely or chronically (2 weeks), alone or in combination with L-DOPA/benserazide (6 mg/kg/6 mg/kg). Acute treatment with CPL500036 reversed the lesion-induced impairments of contralateral forelimb use in the stepping and cylinder tests but did not influence deficits in the vibrissae test and the lesion-induced catalepsy. Moreover, CPL500036 did not diminish the therapeutic effects produced by acute and chronic treatment with L-DOPA in these tests. The present study suggests a potential use of CPL500036 as a co-treatment to L-DOPA in PD therapy.
Assuntos
Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson Secundária/tratamento farmacológico , Inibidores de Fosfodiesterase/uso terapêutico , Diester Fosfórico Hidrolases/metabolismo , Animais , Antiparkinsonianos/farmacologia , Modelos Animais de Doenças , Neurônios GABAérgicos/efeitos dos fármacos , Humanos , Levodopa/farmacologia , Masculino , Oxidopamina/administração & dosagem , Oxidopamina/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/patologia , Inibidores de Fosfodiesterase/farmacologia , Ratos , Índice de Gravidade de DoençaRESUMO
To examine the extent to which a consensus exists in the scientific community regarding the relationship between exposure to paraquat and Parkinson's disease, a critical review of reviews was undertaken focusing on reviews published between 2006 and the present that offered opinions on the issue of causation. Systematic searches were undertaken of scientific databases along with searches of published bibliographies to identify English language reviews on the topic of paraquat and Parkinson's disease including those on the broader topic of environmental and occupational risk factors for Parkinson's disease. Of the 269 publications identified in the searches, there were twelve reviews, some with meta-analyses, that met the inclusion criteria. Information on methods used by the reviewers, if any, and source of funding was collected; the quality of the reviews was considered. No author of any published review stated that it has been established that exposure to paraquat causes Parkinson's disease, regardless of methods used and independent of funding source. A consensus exists in the scientific community that the available evidence does not warrant a claim that paraquat causes Parkinson's disease. Future research on this topic should focus on improving the quality of epidemiological studies including better exposure measures and identifying specific mechanisms of action. Future reviews of emerging evidence should be structured as systematic narrative reviews with meta-analysis if appropriate.
Assuntos
Herbicidas/toxicidade , Metanálise como Assunto , Paraquat/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnóstico , Revisões Sistemáticas como Assunto/métodos , Animais , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismo , Doença de Parkinson Secundária/metabolismo , Fatores de RiscoAssuntos
COVID-19/complicações , Doença de Parkinson/complicações , SARS-CoV-2 , Adulto , Causalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/etiologia , Fatores de Tempo , Pesquisa Translacional BiomédicaRESUMO
Cranial dural arteriovenous fistula (cDAVF) may rarely lead to parkinsonism and rapid cognitive decline. Dysfunction of the extrapyramidal system and the thalamus, due to venous congestion of the Galenic system with subsequent parenchymal edema, is likely to represent an important pathophysiological mechanism. Here, we report a case of a 57-year-old man with a cDAVF of the straight sinus (Borden type III; DES-Zurich bridging vein shunt [BVS] type with direct, exclusive, and strained leptomeningeal venous drainage [LVD]) and subsequent edema of both thalami, the internal capsule, the hippocampi, the pallidum, and the mesencephalon. Several attempts at venous embolization were unsuccessful, and the neurological condition of the patient further deteriorated with progressive parkinsonism and intermittent episodes of loss of consciousness (KPS 30). A suboccipital mini-craniotomy was performed and the culminal vein was disconnected from the medial tentorial sinus, achieving an immediate fistula occlusion. Three-month follow-up MRI revealed complete regression of the edema. Clinically, parkinsonism remitted completely, allowing for tapering of dopaminergic medication. His cognition markedly improved in further course. The purpose of this report is to highlight the importance of rapid and complete cDAVF occlusion to reverse venous hypertension and prevent progressive clinical impairment. The review of the literature underlines the high morbidity and mortality of these patients. Microsurgical disconnection of the fistula plays an important role in the management of these patients and, surprisingly, has not been reported so far.
Assuntos
Antiparkinsonianos/uso terapêutico , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Craniotomia , Procedimentos Neurocirúrgicos , Doença de Parkinson Secundária/tratamento farmacológico , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Cognição , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/etiologia , Doença de Parkinson Secundária/fisiopatologia , Resultado do TratamentoRESUMO
The sigma 1 receptor (S1R) is widely expressed in the CNS and is mainly located on the endoplasmic reticulum. The S1R is involved in the regulation of many neurotransmission systems and, indirectly, in neurodegenerative diseases. The S1R may therefore represent an interesting neuronal biomarker in neurodegenerative diseases such as Parkinson's (PD) or Alzheimer's diseases (AD). Here we present the characterisation of the S1R-specific 18F-labelled tracer 18F-IAM6067 in two animal models and in human brain tissue. Methods: Wistar rats were used for PET-CT imaging (60 min dynamic acquisition) and metabolite analysis (1, 2, 5, 10, 20, 60 min post-injection). To verify in vivo selectivity, haloperidol, BD1047 (S1R ligand), CM398 (S2R ligand) and SB206553 (5HT2B/C antagonist) were administrated for pre-saturation studies. Excitotoxic lesions induced by intra-striatal injection of AMPA were also imaged by 18F-IAM6067 PET-CT to test the sensitivity of the methods in a well-established model of neuronal loss. Tracer brain uptake was also verified by autoradiography in rats and in a mouse model of PD (intrastriatal 6-hydroxydopamine (6-OHDA) unilateral lesion). Finally, human cortical binding was investigated by autoradiography in three groups of subjects (control subjects with Braak ≤2, and AD patients, Braak >2 & ≤4 and Braak >4 stages). Results: We demonstrate that despite rapid peripheral metabolism of 18F-IAM6067, radiolabelled metabolites were hardly detected in brain samples. Brain uptake of 18F-IAM6067 showed differences in S1R anatomical distribution, namely from high to low uptake: pons-raphe, thalamus medio-dorsal, substantia nigra, hypothalamus, cerebellum, cortical areas and striatum. Pre-saturation studies showed 79-90% blockade of the binding in all areas of the brain indicated above except with the 5HT2B/C antagonist SB206553 and S2R ligand CM398 which induced no significant blockade, indicating good specificity of 18F-IAM6067 for S1Rs. No difference between ipsi- and contralateral sides of the brain in the mouse model of PD was detected. AMPA lesion induced a significant 69% decrease in 18F-IAM6067 uptake in the globus pallidus matching the neuronal loss as measured by NeuN, but only a trend to decrease (-16%) in the caudate putamen despite a significant 91% decrease in neuronal count. Moreover, no difference in the human cortical binding was shown between AD groups and controls. Conclusion: This work shows that 18F-IAM6067 is a specific and selective S1R radiotracer. The absence or small changes in S1R detected here in animal models and human tissue warrants further investigations and suggests that S1R might not be the anticipated ideal biomarker for neuronal loss in neurodegenerative diseases such as AD and PD.
Assuntos
Doença de Alzheimer/diagnóstico , Encéfalo/diagnóstico por imagem , Doença de Parkinson Secundária/diagnóstico , Compostos Radiofarmacêuticos/administração & dosagem , Receptores sigma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Animais , Autorradiografia , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Radioisótopos de Flúor/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Molecular/métodos , Oxidopamina/administração & dosagem , Oxidopamina/toxicidade , Doença de Parkinson Secundária/etiologia , Doença de Parkinson Secundária/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Ratos , Ratos Wistar , Receptor Sigma-1RESUMO
PURPOSE: The purpose of this study was to examine the incidence of Parkinsonism in new users of second-generation antipsychotics (SGAs) in older adults (≥65 years). In the secondary analyses, we examined the risk of Parkinsonism by type and dose of SGA and conducted age-sex interactions. METHOD: This population-based study included older adults who had a new-onset diagnosis of Parkinsonism and who started taking olanzapine, risperidone or quetiapine between 1 January 2005, and 30 December 2016. The Cox proportional hazard (COXPH) model with inverse probability treatment weighted (IPTW) covariates was used to evaluate the risk of new-onset Parkinsonism associated with SGAs, using quetiapine as the reference. We used the Generalized Propensity Score method to evaluate the dose-response risk of Parkinsonism associated with SGAs. RESULTS: After IPTW adjustment for covariates, the COXPH model showed that compared to quetiapine, the use of olanzapine and risperidone were associated with an increased risk of Parkinsonism. The IPTW-hazard ratios are 1.76 (95% confidence interval 1.57-1.97) and 1.31 (95%CI 1.16-1.49), respectively. The dose-response risk of Parkinsonism was highest for olanzapine with a hazard ratio of 1.69 (95%CI 1.40-2.05) and the least for quetiapine with a hazard ratio of 1.22 (95%CI 1.14-1.31). The risk of Parkinsonism in the 65 to 74-year age group was higher for both sexes with risperidone compared to olanzapine, but the risk increased with olanzapine for both sexes in the 85+ age group. CONCLUSION: The study found that the risk of new-onset Parkinsonism in older adults is 31% and 76% higher with risperidone and olanzapine respectively compared to quetiapine.
Assuntos
Antipsicóticos/efeitos adversos , Olanzapina/efeitos adversos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/epidemiologia , Fumarato de Quetiapina/efeitos adversos , Risperidona/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Nova Zelândia/epidemiologia , Doença de Parkinson Secundária/diagnóstico , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVE: The objective of this study is to examine the effectiveness of an accelerometer-based compact system in detecting and quantifying drug-induced parkinsonism (DIP) in patients with schizophrenia. METHOD: A pilot study controlled clinical trial comprising 6 people with schizophrenia and 11 control subjects was conducted at Alfred Health, Melbourne. Participants had their movements assessed using Barnes Akathisia Rating Scale (BARS), Simpson Angus Scale (SAS) and Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) followed by an assessment of gait using three triaxial accelerometers. RESULTS: Median BARS, SAS, MDS-UPDRS III and accelerometer scores were significantly higher for patients with schizophrenia than controls. Accelerometers detected three times more rest tremor than clinical rating scales. Patients with schizophrenia had 70% of their dynamic acceleration at frequencies between 4 and 10 Hz, which is almost twice that observed in the control population (38%). Accelerometer scores were significantly correlated with BARS scores. CONCLUSION: Accelerometers were able to accurately detect patients with DIP better than some clinical rating scale including the SAS. Further larger-scale studies must be conducted to further demonstrate the accuracy of accelerometers in detecting DIP.
Assuntos
Acelerometria/métodos , Antipsicóticos/efeitos adversos , Doença de Parkinson Secundária/diagnóstico , Adulto , Antipsicóticos/uso terapêutico , Feminino , Marcha/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson Secundária/induzido quimicamente , Projetos Piloto , Valor Preditivo dos Testes , Esquizofrenia/tratamento farmacológicoAssuntos
Apatia , Doenças dos Gânglios da Base/complicações , Neoplasias Encefálicas/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Doença de Parkinson Secundária/etiologia , Idoso , Doença Cerebrovascular dos Gânglios da Base/complicações , Doença Cerebrovascular dos Gânglios da Base/diagnóstico por imagem , Doenças dos Gânglios da Base/diagnóstico por imagem , Doenças dos Gânglios da Base/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/metabolismo , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Diagnóstico Diferencial , Progressão da Doença , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/tratamento farmacológico , Doença de Parkinson Secundária/metabolismoRESUMO
INTRODUCTION: The diagnosis of vascular parkinsonism (VP) is based on a series of clinical criteria and neuroimaging findings. An increase in transcranial Doppler ultrasonography pulsatility index (PI) has been described as a frequent finding in patients with VP. We aimed to confirm this association and to determine the PI value with the highest sensitivity and specificity for diagnosis of VP. METHOD: PI was determined in all patients admitted to Hospital Universitari i Politècnic La Fe due to parkinsonism between January 2012 and June 2016. We assessed the probability of having VP based on PI values in patients with a definite diagnosis of either VP or idiopathic Parkinson's disease (IPD). A ROC curve was created to determine the PI value with the highest sensitivity and specificity. RESULTS: We assessed a total of 146 patients with suspected parkinsonism; 54 (37%) were diagnosed with IPD and 15 (10%) with VP. Patients with VP were significantly older than those with IPD (mean age of 79 vs 68.5, P=.00144) and had a higher PI (median of 1.29 [IQR: 1.09-1.38] vs 0.96 [IQR: 0.89-1.16], P=.01328). In our sample, a PI of 1.09 conferred 84% sensitivity and 70% specificity. CONCLUSIONS: In our series, the PI was significantly higher in patients with VP than in those with IPD. We therefore support the use of transcranial Doppler ultrasonography for the initial assessment of elderly patients with akinetic-rigid syndrome.
Assuntos
Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson/diagnóstico , Ultrassonografia Doppler Transcraniana/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neuroimagem , Doenças VascularesRESUMO
In addition to neurodegenerative disorders, there are many secondary forms of parkinsonism. The most common cause for secondary parkinsonism is the intake of distinct drugs. Neuroleptics and calcium channel blockers have been mainly described to induce parkinsonism, but also other drugs were suspected to cause or worsen parkinsonism. Another common cause for secondary parkinsonism are vascular lesions (i.e. vascular parkinsonism). Furthermore, also brain tumors have been described as rare causes for parkinsonism. Moreover, parkinsonism can be caused by chronic traumatic encephalopathy, which is a special case, since secondary insults to the brain leads to the occurrence of a neuropathologically defined disease. Other rare causes for secondary parkinsonism are lesions caused by infectious or immunological diseases as well as toxins or street drugs.
Assuntos
Lesões Encefálicas Traumáticas/complicações , Neoplasias Encefálicas/complicações , Transtornos Cerebrovasculares/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Doença de Parkinson Secundária/etiologia , Doença de Parkinson Secundária/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Humanos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnósticoRESUMO
BACKGROUND: Parkinson's disease (PD) and drug-induced parkinsonism (DIP) are the major diseases of parkinsonism. To better understand parkinsonism, we aimed to assess the prevalence and incidence of PD and DIP in Korea from 2012 to 2015. METHODS: We used the Health Insurance Review and Assessment Service database, which covers the entire population in Korea. We used claims during 2011-2015 to assess epidemiology of PD and DIP during 2012-2015. Retrospective cross-sectional study design was employed to assess prevalence, whereas retrospective cohort study design was used to determine incidence. Patients with at least one claim with ICD-10 G20 and who received antiparkinsonian drugs for at least 60 days were classified as having PD. We excluded patients with antiparkinsonian drugs that can be used for indications other than PD. Patients with at least one claim with ICD-10 G211 or G251 during the prescription period of drugs that are frequently related with DIP were classified as having DIP. Incident cases had a disease-free period of 1 year before diagnosis. To evaluate the significance of changes in the prevalence or incidence over time, Poisson regression was used to determine p for trend. RESULTS: The prevalence of PD increased from 156.9 per 100,000 persons in 2012 to 181.3 per 100,000 persons in 2015 (p for trend< 0.0001). The incidence of PD decreased steadily from 35.4 per 100,000 person-years in 2012 to 33.3 per 100,000 person-years in 2015 (p for trend< 0.0001). The prevalence of DIP increased from 7.3 per 100,000 persons in 2012 to 15.4 per 100,000 persons in 2015 (p for trend< 0.0001) and the incidence of DIP increased from 7.1 per 100,000 person-years in 2012 to 13.9 per 100,000 person-years in 2015 (p for trend< 0.0001). CONCLUSIONS: Our study suggests that the incidence of PD has gradually decreased whereas, the incidence of DIP increased from 2012 to 2015. Further studies are warranted to examine possible causes of increased DIP incidence in order to develop management strategy for parkinsonism.
Assuntos
Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Idoso , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/epidemiologia , Prevalência , República da Coreia/epidemiologia , Estudos RetrospectivosRESUMO
Objective: This research is devoted to intracerebral transcatheter laser photobiomodulation therapy (PBMT) in the treatment of ischemic and neurodegenerative lesions of cerebral white matter in patients with Binswanger's disease (BD) and vascular parkinsonism (VP) in comparison with conservative treatment methods. Background: Recent studies have shown PBMT high potential in the treatment of various cerebral lesions. Materials and methods: Twenty-seven patients with BD, 58-81 years of age (mean age 78), 17 (62.96%) men, and 10 (27.04%) women. Of these, test group 1-14 (51.85%) patients-underwent intracerebral transcatheter laser PBMT, and control group 1-13 (48.15%) patients-had conservative treatment. Besides, 62 patients with VP, 52-80 years of age (mean age 77), 48 (77.42%) men, and 14 (22.58%) women. Of these, test group 2-37 (59.68%) patients-underwent intracerebral transcatheter laser PBMT, and control group 2-25 (40.32%) patients-had conservative treatment. Results: Good and satisfactory clinical results were obtained in Test group 1 and Test group 2 patients in 49 (92.45%) cases, with a persistent decrease of dementia and motor impairment, and recovery of cognitive functions and daily life activity. Control group 1 and Control group 2 patients showed a satisfactory clinical result in 6 (15.79%) cases. Persistent positive dynamics was not observed. Conclusions: Intracerebral transcatheter laser PBMT is a pathogenetically justified, effective treatment for BD and VP; it restores cerebral collateral and capillary blood supply, improves microcirculation, restores cellular and tissue metabolism, stimulates neurogenesis, and causes regenerative processes in the brain.
Assuntos
Encéfalo/efeitos da radiação , Cateterismo/métodos , Demência Vascular/diagnóstico , Terapia com Luz de Baixa Intensidade/métodos , Doença de Parkinson Secundária/radioterapia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Disfunção Cognitiva/fisiopatologia , Tratamento Conservador/métodos , Demência Vascular/terapia , Relação Dose-Resposta à Radiação , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson Secundária/diagnóstico , Prognóstico , Valores de Referência , Medição de Risco , Resultado do TratamentoRESUMO
PURPOSE: Discontinuation of offending drugs can prevent drug-induced parkinsonism (DIP) before it occurs and reverse or cure it afterwards. The aim of this study was to investigate the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide claims data. MATERIALS AND METHODS: We selected DIP patients of ages ranging from 40 to 100 years old with the G21.1 code from the Korean National Service Health Insurance Claims database from 2009 to 2015. The annual standardized prevalence of DIP was explored from 2009 to 2015. Trends were estimated using the compound annual growth rate (CAGR) and the Cochran-Armitage test for DIP over the course of 6 years. Additionally, the utilization of offending drugs was analyzed. RESULTS: The annual prevalence of DIP was 4.09 per 100000 people in 2009 and 7.02 in 2015 (CAGR: 9.42%, p<0.001). Levosulpiride use before and after DIP diagnosis showed a clear trend for decreasing utilization (CAGR: -5.4%, -4.3% respectively), whereas the CAGR for itopride and metoclopramide increased by 12.7% and 6.4%, respectively. In 2015, approximately 46.6% (858/1840 persons) of DIP patients were prescribed offending drugs after DIP diagnosis. The most commonly prescribed causative drug after DIP diagnosis was levosulpiride. CONCLUSION: The prevalence of DIP has increased. To prevent or decrease DIP, we suggest that physicians reduce prescriptions of benzamide derivatives that have been most commonly used, and that attempts be made to find other alternative drugs. Additionally, the need for continuing education about offending drugs should be emphasized.
Assuntos
Doença de Parkinson Secundária/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Benzamidas/efeitos adversos , Compostos de Benzil/efeitos adversos , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson Secundária/diagnóstico , Prevalência , República da Coreia/epidemiologia , Sulpirida/efeitos adversos , Sulpirida/análogos & derivados , Adulto JovemRESUMO
BACKGROUND: Parkinson's disease is a disorder growing in prevalence, disability, and deaths. Healthcare databases provide a 'real-world' perspective for millions of individuals. We envisioned helping accelerate drug discovery by using these databases. OBJECTIVES: The objectives of this study were to assess the association of marketed medications with the risk of parkinsonism in four US claims databases and to evaluate the consistency of the association of ß-adrenoreceptor modulation with parkinsonism. METHODS: The study was conducted using a self-controlled cohort design in which subjects served as their own control. The time from treatment initiation until discontinuation or end of observation was the exposed period and a similar time preceding medication was the unexposed period. Medications were studied at ingredient and class level. The incidence rate ratio (IRR) and combined IRR were calculated. RESULTS: We assessed 2181 drugs and 117,015,066 people. Diphenhydramine, isradipine, methylphenidate, armodafinil, and modafinil were associated with reduced risk for parkinsonism in at least two databases. Armodafinil, modafinil, methylphenidate, and the ß-agonist albuterol were associated with a 56%, 54%, 39%, and 17% reduction in the risk of having parkinsonism, respectively. Isradipine results were heterogeneous and no significant association was found. Propranolol was associated with a 32% increased risk, the only ß-adrenoceptor antagonist (ß-blocker) associated with an increased risk. CONCLUSIONS: Armodafinil, modafinil, and methylphenidate were associated with a decreased risk of parkinsonism, as were ß-agonists. Of the ß-blockers, only propranolol was associated with increased risk. Healthcare database analyses that incorporate scientific rigor provide insight and direction for drug discovery efforts. These findings show association not causality; however, they offer considerable support to the association between ß-adrenergic receptor modulation and risk of Parkinson's disease.