RESUMO
PURPOSE: Dopamine transporters (DAT) modulate pre-synaptic dopamine and physiological functions such as movement and reward. DAT also mirrors disease state in neurological disorders, rendering it an essential diagnostic target. [18F]PR04.MZ is a new PET imaging agent for DAT with an improved affinity and selectivity profile, for which we here describe the complete pharmacokinetic evaluation in healthy controls. METHODS: Thirty-two healthy subjects underwent T1-weighted MRI and dynamic PET scans for 180 min with arterial blood sampling (n = 5) or 90 min without blood sampling (n = 25) after injection of 197.6 ± 12.2 MBq [18F]PR04.MZ. Blood and plasma metabolite analysis were performed. MRI-based normalization of brain images, delineation of VOIs, and kinetic modeling was conducted to determine distribution volumes (Vt) and binding potentials (BPnd). The impact of scan duration was evaluated and repeated PET scans were performed to assess test-retest variability (n = 5). A static imaging protocol has been validated for clinical applications. RESULTS: [18F]PR04.MZ showed rapid metabolization in circulation, very high uptake in striatum and midbrain, and very low non-specific binding. The two-tissue compartment model 2TCM provided best fits for measured time-activity-curves and calculated Vts in putamen, caudate, substantia nigra pars compacta (SNpc), and cerebellar cortex were 11.83, 9.73, 2.12, and 0.57, respectively. All non-invasive models correlated well with BPnd values derived from 2TCM but underestimated DAT availability by about 28-33%. Of those, simplified reference tissue model (SRTM) provided the best fits, lowest Akaike Information Criteria values, and BPnd values of 14.82, 11.95, and 2.63 in putamen, caudate, and SNpc, respectively. BPnd estimates for striatal regions and SNpc were stable between 90 and 130 min post-injection. Test-retest results were excellent, showing low variability in all and excellent reliability in most relevant regions. Static imaging from 60 to 90-min post-injection is a viable alternative for quantification. CONCLUSIONS: [18F]PR04.MZ is a PET tracer with very high affinity, selectivity, and specific uptake in striatum and midbrain. 2TCM and SRTM provide good fits, high and stable Vts or BPnds, and good test-retest reliability for precise quantification of DAT in human subjects.
Assuntos
Dopamina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Humanos , Tomografia por Emissão de Pósitrons , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: There are many patients with Parkinson's disease who have a limited response to conventional pharmacological treatment. The use of stem cells has been postulated as an alternative, although its effectiveness remains a matter of controversy. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews including 21 studies overall, of which three were randomized trials. We concluded it is not clear whether stem cells have any effect on the symptoms of Parkinson's disease because the certainty of the available evidence is very low.
INTRODUCCIÓN: Muchos pacientes con enfermedad de Parkinson tienen una respuesta limitada con el tratamiento farmacológico convencional. Se ha postulado el uso de células madre como una alternativa, aunque su efectividad sigue siendo un tema de controversia. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron 21 estudios primarios, de los cuales tres corresponden a ensayos aleatorizados. Concluimos que no está claro si las células madre podrían tener algún efecto sobre la sintomatología de la enfermedad de Parkinson porque la certeza de la evidencia disponible es muy baja.
Assuntos
Doença de Parkinson/terapia , Transplante de Células-Tronco/métodos , Bases de Dados Factuais , Humanos , Doença de Parkinson/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
INTRODUCTION: It has been proposed that acupuncture has several benefits for patients with Parkinsons disease. However, its real clinical effect is still under discussion. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified nine systematic reviews including 53 studies overall, of which 45 were randomized trials. We concluded acupuncture might have a small effect in improving motor symptoms and disability in Parkinsons disease, but the certainty of the evidence is low.
INTRODUCCIÓN: Se postula que la acupuntura podría tener diversos beneficios para pacientes con enfermedad de Parkinson. No obstante, su real efectividad clínica aún es discutida. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos nueve revisiones sistemáticas que en conjunto incluyen 53 estudios primarios, de los cuales 45 corresponden a ensayos aleatorizados. Concluimos que la acupuntura podría tener un efecto mínimo en mejorar los síntomas motores y la discapacidad en la enfermedad de Parkinson, pero la certeza de la evidencia es baja.
Assuntos
Terapia por Acupuntura/métodos , Doença de Parkinson/terapia , Bases de Dados Factuais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
It is postulated cannabinoids may have benefits in Parkinson's disease. However, its actual clinical effectiveness is still discussed. To answer this question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We identified six systematic reviews including eight studies overall, of which four were randomized trials relevant for the question of interest. We extracted data from the systematic reviews, reanalyzed data of primary studies included in these reviews, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded cannabinoids probably do not decrease symptoms in Parkinsons disease or dyskinesia, and probably are associated to frequent adverse effects in patients with Parkinsons disease.
Se postula que los cannabinoides pudieran tener beneficios en la enfermedad de Parkinson. No obstante, su real efectividad clínica aún es discutida. Para responder a esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Identificamos seis revisiones sistemáticas que en conjunto incluyen ocho estudios, de los cuales cuatro corresponden a ensayos aleatorizados. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los cannabinoides probablemente no disminuyen los síntomas ni las discinesias, y se asocian a efectos adversos frecuentes en pacientes con enfermedad de Parkinson.
Assuntos
Antiparkinsonianos/uso terapêutico , Canabinoides/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Canabinoides/efeitos adversos , Bases de Dados Factuais , Humanos , Doença de Parkinson/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Secondary paroxysmal dyskinesias (SPDs) are short, episodic, and recurrent movement disorders, classically related to multiple sclerosis (MS). Carbamazepine is effective, but with risk of adverse reactions. We identified 7 patients with SPD among 457 MS patients (1.53%). SPD occurred in face ( n = 1), leg ( n = 2), or arm +leg ( n = 4) several times during the day. Magnetic resonance imaging (MRI) showed new or enhancing lesions in thalamus ( n = 1), mesencephalic tegmentum ( n = 1), and cerebellar peduncles ( n = 5). Patients were treated with clonazepam and then acetazolamide ( n = 1), acetazolamide ( n = 5), or levetiracetam ( n = 1) with response within hours (acetazolamide) to days (levetiracetam). No recurrences or adverse events were reported after a median follow-up of 33 months.
Assuntos
Anticonvulsivantes/farmacologia , Cerebelo/diagnóstico por imagem , Discinesias , Distonia , Esclerose Múltipla , Tegmento Mesencefálico/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Acetazolamida/farmacologia , Adulto , Anticonvulsivantes/administração & dosagem , Clonazepam/farmacologia , Discinesias/diagnóstico por imagem , Discinesias/tratamento farmacológico , Discinesias/etiologia , Discinesias/fisiopatologia , Distonia/diagnóstico por imagem , Distonia/tratamento farmacológico , Distonia/etiologia , Distonia/fisiopatologia , Feminino , Seguimentos , Humanos , Levetiracetam , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/fisiopatologia , Piracetam/análogos & derivados , Piracetam/farmacologia , Resultado do TratamentoRESUMO
BACKGROUND: Parkinson disease (PD) is the second more common neurodegenerative disorder and determines a loss in quality of life, caregiver burden and increased mortality in those affected. AIM: To determine the rates of mortality due to Parkinson disease in Chile. MATERIAL AND METHODS: Data were collected from death certificates between 1997 and 2008. Mortality rates were calculated and the mortality trend was established along the study period, and analyzed by age, sex and geographic región of Chile. RESULTS: There was a steady increase in mortality over the years, particularly since 2001 (r²= 0.85, p < 0.01). The increase in mortality rates was 0.25 per 100.000 habitants/year (r²: 0.89, p < 0.01). Mortality was always higher in men and in those older than 80 years. The highest rate (per 100,000 habitants) in Chile was observed in the región of Valparaíso (2.4) while the lowest was in Antofagasta (0.8) (t = 3.72, p < 0.05). CONCLUSIONS: Mortality associated with PD has increased progressively, consistent with the expected increase in prevalence of the disease in the population.
Assuntos
Doença de Parkinson/mortalidade , Idoso , Idoso de 80 Anos ou mais , Chile/epidemiologia , Atestado de Óbito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por SexoRESUMO
BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with a high risk of developing Parkinson's disease (PD). Higher urate levels are associated with a lower risk of PD. We conducted a study to evaluate plasma urate levels in patients with RBD and their role in the development of PD. METHODS: We evaluated plasma urate levels in a cohort of 24 patients with idiopathic RBD. Patients were divided into 2 groups according to the presence or absence of PD. Other known markers of the risk of developing PD, such as olfaction testing, and substantia nigra (SN) hyperechogenicity, were evaluated in the 2 groups. RESULTS: No differences were observed regarding age, years of evolution of the RBD, SN hyperechogenicity, or plasma urate levels between the 2 groups. In patients without PD, there was a positive correlation between years of evolution of RBD and the levels of uric acid (R(2) =0.88). Patients without PD and those who had more than 5 years of RBD exhibited higher levels of uric acid than patients with PD (P=0.02). CONCLUSIONS: Higher levels of plasma urate were associated with a longer duration of RBD without converting to PD. Future prospective studies would be needed to confirm this finding. Disorder Society
Assuntos
Transtorno do Comportamento do Sono REM/sangue , Ácido Úrico/sangue , Feminino , Humanos , Modelos Lineares , Masculino , Doença de Parkinson , Polissonografia , Transtorno do Comportamento do Sono REM/complicações , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
Background: Parkinson disease (PD) is the second more common neurodegene-rative disorder and determines a loss in quality oflife, caregiver burden and increased mortality in those affected. Aim: To determine the rates of mortality due to Parkinson disease in Chile. Material andMethods: Data were collected from death certificates between 1997 and 2008. Mortality rates were calculated and the mortality trend was established along the study period, and analyzed by age, sex and geographic región of Chile. Results: There was a steady increase in mortality over the years, particularly since2001 (r²= 0.85, p < 0.01). The increase in mortality rates was 0.25per 100.000 habitants/year (r²: 0.89, p < 0.01). Mortality was always higher in men and in those older than 80years. The highest rate (per 100,000 habitants) in Chile was observed in the región of Valparaíso (2.4) while the lowest was in Antofagasta (0.8) (t = 3.72, p < 0.05). Conclusions: Mortality associated with PD has increased progressively, consistent with the expected increase in prevalence ofthe disease in the population.