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1.
Int J Mol Sci ; 21(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333774

RESUMO

Atypical antipsychotic drugs were introduced in the early 1990s. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics are effective against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic but also in affective disorders, on their own or as adjuncts to antidepressant drugs. This review presents the neural mechanisms of currently existing atypical antipsychotics and putative antipsychotics currently being investigated in preclinical and clinical studies and how these relate to their effectiveness in mood disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD). Typical antipsychotics act almost exclusively on the dopamine system. Atypical drugs, however, modulate serotonin (5-HT), norepinephrine, and/or histamine neurotransmission as well. This multimodal mechanism of action putatively underlies the beneficial effect of atypical antipsychotics in mood and anxiety disorders. Interestingly, novel experimental drugs having dual antipsychotic and antidepressant therapeutic potential, such as histamine, adenosine, and trace amine-associated receptors (TAAR) ligand, are also characterized by a multimodal stimulatory effect on central 5-HT, norepinephrine, and/or histamine transmission. The multimodal stimulatory effect on central monoamine neurotransmission may be thus primarily responsible for the combined antidepressant and antipsychotic therapeutic potential of certain central nervous system (CNS) drugs.


Assuntos
Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Neurônios/efeitos dos fármacos , Antidepressivos/farmacologia , Antipsicóticos/farmacologia , Dopaminérgicos/farmacologia , Dopaminérgicos/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Histamínicos/farmacologia , Histamínicos/uso terapêutico , Humanos , Receptores Adrenérgicos/efeitos dos fármacos , Receptores Purinérgicos/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Receptores de Serotonina/fisiologia
2.
Rev. neurol. (Ed. impr.) ; 71(11): 407-420, 1 dic., 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-198940

RESUMO

INTRODUCCIÓN: Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. DESARROLLO: Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. CONCLUSIÓN: El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motora


INTRODUCTION. Motor fluctuations are one of the most common complications of Parkinsons disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT. Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION. The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations


Assuntos
Humanos , Consenso , Técnica Delfos , Doença de Parkinson/tratamento farmacológico , Transtornos Motores/tratamento farmacológico , Transtornos Motores/fisiopatologia , Doença de Parkinson/fisiopatologia , Levodopa/uso terapêutico , Dopaminérgicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Estimulação Encefálica Profunda
3.
Medicine (Baltimore) ; 99(33): e21753, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872068

RESUMO

RATIONAL: Tyrosine hydroxylase deficiency (THD) is a rare cause of dopa-responsive dystonia (DRD). Although the symptoms of DRD may be improved by treatment with L-dopa, the low morbidity of THD can lead to its misdiagnosis. Thus, it is important for physicians to be aware of THD as a cause of DRD. PATIENT CONCERNS: We report 3 cases of THD. A 5-year-old boy with DRD was diagnosed with THD and found to have compound heterozygous mutations of the TH gene, including TH:c.647G>C from his mother and TH:c.646G>A from his father. Two female siblings also were found to have TH:c.698G>A from their mother and TH:c.710T>C from their father. The younger daughter, at age 3.5 years, was diagnosed with DRD caused by THD, and then the diagnosis of the older daughter, at age 11 years, was changed from cerebral palsy to DRD caused by THD. DIAGNOSIS: The diagnosis of dopa-responsive dystonia caused by tyrosine hydroxylase deficiency was determined by whole exome sequencing. INTERVENTION: They all treated with low dose levodopa and benserazide tablets. OUTCOMES: The boy had a very good therapeutic effect, and he could walk very well by the second day of treatment. The younger sister of the siblings had a partial therapeutic effect, but her elder sister was only little effective with a milder improvement of dystonia and improvement of myodynamia. CONCLUSION: The characteristics of THD are heterogeneous, and its phenotypes are classified as type A or type B according to increasing severity. Generally, L-dopa has a good therapeutic effect in cases with type A phenotypes. We reviewed 87 cases of reported in the literature and found that c.698G>A and c.707T>C are hot spot mutations. Changes on cerebral magnetic resonance imaging were nonspecific. Analysis of neurotransmitter levels in cerebrospinal fluid is an invasive means of achieving a biochemical diagnosis.


Assuntos
Distúrbios Distônicos/congênito , Tirosina 3-Mono-Oxigenase/genética , Benserazida/uso terapêutico , Criança , Pré-Escolar , Dopaminérgicos/uso terapêutico , Distúrbios Distônicos/complicações , Distúrbios Distônicos/tratamento farmacológico , Distúrbios Distônicos/genética , Humanos , Levodopa/uso terapêutico , Masculino
4.
Medicine (Baltimore) ; 99(33): e21822, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872083

RESUMO

Amantadine is currently recommended for use in patients of posttraumatic brain injury with unconsciousness. However, the application of amantadine in consciousness disturbance after cerebral hemorrhage has only been rarely reported. This allows for a further exploration of the role of amantadine in the treatment of PVS resulting from severe cerebral hemorrhage.Retrospective cohort study from 1/2015 to 7/2019 in Beijing Chaoyang hospital. We included adult patients treated with amantadine after severe cerebral hemorrhage in PVS. Primary outcome was time of consciousness recovery and Glasgow Out Scale scores after 5 months from onset. We compared characteristics and outcomes to a control cohort. matched on age, Coma Recovery Scale-Revised score, volume and location of hemorrhage.Among the 12 patients who received amantadine treatment, 6 patients regained consciousness (50%) after 5 months of disease onset, but were still severely disabled. Besides, the time for regaining consciousness was within 3 months of disease onset. The remaining 6 patients were still in a PVS. Compared with the amantadine group, the consciousness recovery rate (50% vs 33.3%, P = .68) after 5 months in the nested control group was not significantly different. The awakening time for patients in the amantadine group was earlier than the control group (100% vs 25%, P = .03).In this study, amantadine can accelerate the recovery of consciousness in patients following severe cerebral hemorrhage. We recommend further randomized controlled studies to determine the efficacy of amantadine.


Assuntos
Amantadina/uso terapêutico , Hemorragia Cerebral/complicações , Dopaminérgicos/uso terapêutico , Estado Vegetativo Persistente/tratamento farmacológico , Adulto , Idoso , Hemorragia Cerebral/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/etiologia , Estudos Retrospectivos
5.
Rev. ORL (Salamanca) ; 11(3): 273-281, jul.-sept. 2020.
Artigo em Espanhol | IBECS | ID: ibc-197897

RESUMO

El hipertiroidismo es una enfermedad común que afecta a un 0.2 % de la población en Europa. Aun siendo un síndrome, el tratamiento varía dependiendo de la causa. Los mecanismos patogénicos de cada una de las etiologías dictan la selección del tratamiento, siendo el hipertiroidismo un buen modelo de medicina de precisión, por cuanto una vez conocida la patogenia se personaliza el tratamiento. En este capítulo se considera el tratamiento de las causas más comunes como son la enfermedad de Graves-Basedow, el bocio multinodular y adenoma tóxico, causas menos frecuentes que incluyen diverso tipo de tiroiditis y causas raras como los tirotropinomas, e hipertiroidismo por patologías obstétricas y ginecológicas. Para el tratamiento médico de estas condiciones disponemos de un arsenal que incluye drogas antitiroideas, beta-bloqueadores, glucocorticoides, análogos de la somatostatina, agonistas dopaminérgicos, ácido iopanoico e, incluso, agentes antineoplásicos. El tratamiento con radioyodo es objeto de otro trabajo aparte


Hyperthyroidism is a rather common disease that affects 0.2 % of general population in Europe. There are many causes as well as various pathogenic mechanisms inducing a hypersecretion of thyroid hormones. Therefore, treatments are selected for each cause to obtain the highest therapeutic benefit. Is this chapter we consider the treatment of common causes such as Graves-disease, toxic multinodular goiter, toxic adenoma and other more infrequent entities such as several subtypes of thyroiditis and, finally, we briefly comment on rare cases of thyroid hyperfunction


Assuntos
Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/terapia , Doença de Graves/diagnóstico , Bócio/diagnóstico , Tireoidite/diagnóstico , Tireoidite/tratamento farmacológico , Estruma Ovariano/diagnóstico , Hipertireoidismo/epidemiologia , Medicina de Precisão , Tireoidite/etiologia , Dipirona/uso terapêutico , Dopaminérgicos/uso terapêutico
6.
Medicine (Baltimore) ; 99(32): e21578, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769905

RESUMO

Impulsivity is a frequent non-motor symptom in Parkinson disease (PD). It comprises psycho-behavioral alterations that negatively impact quality of life. Dopaminergic treatments underpin many impulsive controls disorders however, side effects, such as increased impulsivity, are described also after neurosurgical procedure of deep brain stimulation (DBS). We investigated the effect of deep brain stimulation on psycho-behavioral alterations and quality of life (QoL) in PD patients, analyzing, also, the role of dopaminergic therapies.Twenty idiopathic PD patients with and 20 idiopathic PD patients without DBS were included in the study. All patient underwent to neuropsychological assessment for a screening of executive functions, impulsivity, anxiety and depressive symptoms and QoL.Differences were found between DBS and no DBS groups and in term of dopaminergic therapies. The comparison between 2 groups showed a greater motor and attentional impulsivity in DBS patients. Moreover, this impulsivity worse QoL and interpersonal relationships. The combination of Levodopa and dopamine agonists exerted a great impact on impulsivity behavior.The emergence of postoperative impulsivity seems to be a neurostimulator phenomenon related to the computational role of the subthalamic nucleus in modulation of behavior.


Assuntos
Estimulação Encefálica Profunda/normas , Dopaminérgicos/uso terapêutico , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida/psicologia , Estatísticas não Paramétricas , Núcleo Subtalâmico/fisiologia
7.
Neurology ; 95(11): e1461-e1470, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32651292

RESUMO

OBJECTIVE: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.


Assuntos
Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tremor/tratamento farmacológico , Acelerometria , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Resistência a Medicamentos/fisiologia , Feminino , Seguimentos , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/tratamento farmacológico , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Resultado do Tratamento , Tremor/diagnóstico por imagem , Tremor/fisiopatologia
8.
Mult Scler Relat Disord ; 42: 102163, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388458

RESUMO

Facing the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to find protective or curable drugs to prevent or to stop the course of the coronavirus SARS-CoV-2 infection. Recent evidence accumulates that adamantanes, widely used in different neurological diseases, could be repurposed for COVID-19. We hereby report on a questionnaire-based study performed to assess severity of COVID-19 in patients suffering from multiple sclerosis (n=10), Parkinson's disease (n=5) or cognitive impairment (n=7). In all patients infection with SARS-CoV-2 was confirmed by rtPCR of nasopharyngeal swabs. They were receiving treatment with either amantadine (n=15) or memantine (n=7) in stable registered doses. All of them had two-week quarantine since documented exposure and none of them developed clinical manifestations of infectious disease. They also did not report any significant changes in neurological status in the course of primary nervous system disease. Above results warrant further studies on protective effects of adamantanes against COVID-19 manifestation, especially in subjects suffering from neurological disease.


Assuntos
Amantadina/uso terapêutico , Infecções Assintomáticas , Disfunção Cognitiva/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Dopaminérgicos/uso terapêutico , Memantina/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Adamantano/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Disfunção Cognitiva/complicações , Infecções por Coronavirus/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Pandemias , Doença de Parkinson/complicações , Pneumonia Viral/complicações , Fatores de Proteção , Índice de Gravidade de Doença
9.
Arq Neuropsiquiatr ; 78(4): 199-205, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32294746

RESUMO

BACKGROUND: Motor Imagery (MI) represents the cognitive component of the movement and recruits dopaminergic systems. OBJECTIVE: To investigate the role of dopaminergic system through the action of methylphenidate and risperidone over beta coherence during execution, action observation and motor imagery. METHODS: Electroencephalography (EEG) data were recorded before and after the substance intake. For statistical analysis, a three-way ANOVA was used to identify changes in beta coherence induced by the group, task and the moment variables. Statistical significance was set at p≤0.007. RESULTS: We found a main effect for group for C3/CZ, and a main effect for task for CZ/C4 pairs of electrodes. Furthermore, significant differences were found in the post-drug administration between groups for C3/CZ pair of electrodes, and between task for C4/CZ pair of electrodes. CONCLUSION: The administration of methylphenidate and risperidone was able to produce electrocortical changes of the cortical central regions, even when featuring antagonistic effects on the dopaminergic pathways. Moreover, the execution task allowed beta-band modulation increase.


Assuntos
Dopaminérgicos/uso terapêutico , Imagens, Psicoterapia , Adulto , Eletroencefalografia , Humanos , Movimento
11.
Arq. neuropsiquiatr ; 78(4): 199-205, Apr. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098082

RESUMO

Abstract Background: Motor Imagery (MI) represents the cognitive component of the movement and recruits dopaminergic systems. Objective: To investigate the role of dopaminergic system through the action of methylphenidate and risperidone over beta coherence during execution, action observation and motor imagery. Methods: Electroencephalography (EEG) data were recorded before and after the substance intake. For statistical analysis, a three-way ANOVA was used to identify changes in beta coherence induced by the group, task and the moment variables. Statistical significance was set at p≤0.007. Results: We found a main effect for group for C3/CZ, and a main effect for task for CZ/C4 pairs of electrodes. Furthermore, significant differences were found in the post-drug administration between groups for C3/CZ pair of electrodes, and between task for C4/CZ pair of electrodes. Conclusion: The administration of methylphenidate and risperidone was able to produce electrocortical changes of the cortical central regions, even when featuring antagonistic effects on the dopaminergic pathways. Moreover, the execution task allowed beta-band modulation increase.


Resumo Introdução: A imagética motora (IM) representa o componente cognitivo do movimento e recruta os sistemas dopaminérgicos. Objetivo: Investigar o papel do sistema dopaminérgico por meio da ação do metilfenidato e da risperidona sobre a coerência em beta durante a execução, observação de ação e imagética motora. Métodos: Os dados de eletroencefalografia (EEG) foram registrados antes e depois da ingestão das substâncias. Para a análise estatística, uma ANOVA de três vias foi utilizada para identificar mudanças na coerência beta induzidas pelas variáveis grupo, tarefa e momento. A significância estatística foi estabelecida em p≤0,007. Resultados: Encontramos um efeito principal para o grupo C3/CZ e um efeito principal para a tarefa nos pares de eletrodos CZ/C4. Além disso, diferenças significativas foram encontradas após a administração da droga entre os grupos para o par de eletrodos C3/CZ e entre tarefa para o par de eletrodos C4/CZ. Conclusão: A administração de metilfenidato e risperidona foi capaz de produzir alterações eletrocorticais das regiões somatomotoras, mesmo apresentando efeitos antagônicos nas vias dopaminérgicas. Além disso, a tarefa de execução provocou maior modulação da banda beta.


Assuntos
Humanos , Adulto , Dopaminérgicos/uso terapêutico , Imagens, Psicoterapia , Eletroencefalografia , Movimento
12.
Neuropsychology ; 34(5): 551-559, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32202819

RESUMO

OBJECTIVE: Dopamine agonists are the main pharmacological intervention for the motor symptoms of Parkinson's disease (PD). However, dopaminergic medication has been associated with disinhibitory psychopathology in some patients. The aim of this study was to test the effect of dopaminergic medication on inhibitory control in patients with PD using the paced Random Number Generation task (RNG), which requires inhibition of prepotent counting in series to produce a random sequence of numbers. METHOD: Twenty-three PD patients performed RNG on and off dopaminergic medication. Cognitive load was manipulated by performing RNG at faster (1Hz) and slower (0.5 Hz) rates. For RNG, two scores (CS1 and CS2) were derived, which are considered indices of more automatic and more controlled counting, respectively. RESULTS: There were no main effects of medication on RNG performance. There was a significant main effect of cognitive load on CS1, with higher CS1 scores at the faster rate (p = <.01). A significant interaction effect between medication and rate (cognitive load; p = .03) followed by post hoc testing, revealed that CS2 scores were higher, on medication, at the slower but not the faster rate. CONCLUSIONS: Patients with PD displayed increased use of more controlled processing strategies on medication at the slowest rate of RNG. Therefore, while dopaminergic medication has been associated with disinhibitory psychopathology, our results suggest that dopamine therapy may enhance some forms of inhibitory cognitive control in PD, but only if there is sufficient time to engage controlled processing strategies. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Antiparkinsonianos/farmacologia , Cognição/efeitos dos fármacos , Dopaminérgicos/farmacologia , Função Executiva/efeitos dos fármacos , Inibição Psicológica , Doença de Parkinson/psicologia , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico
13.
Lancet Neurol ; 19(5): 452-461, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171387

RESUMO

Debate is ongoing regarding when, why, and how to initiate pharmacotherapy for Parkinson's disease. Early initiation of dopaminergic therapies does not convey disease-modifying effects but does reduce disability. Concerns about the development of motor complications arising from the early initiation of levodopa, which led to misconceived levodopa-sparing strategies, have been largely mitigated by the outcomes of the PD MED and Levodopa in Early Parkinson's Disease (LEAP) studies. The LEAP study also showed the potential for early improvement in quality of life, even when disability is negligible. Until more effective methods of providing stable dopamine concentrations are developed, current evidence supports the use of levodopa as initial symptomatic treatment in most patients with Parkinson's disease, starting with low doses and titrating to therapeutic threshold. Monoamine oxidase-B inhibitors and dopamine agonists can be reserved as potential adjunct treatments later in the disease course. Future research will need to establish effective disease-modifying treatments, address whether patients' quality of life is substantially improved with early initiation of treatment rather than a wait and watch strategy, and establish whether new levodopa formulations will delay onset of dyskinesia.


Assuntos
Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Humanos , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento
14.
Cell Tissue Res ; 380(1): 59-66, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31900665

RESUMO

We have tested whether the lack of chromogranins (Cgs) A and B could provoke CNS disorders when combined with an excess of dopamine. We chronically treated (over 6 months) mice lacking both chromogranins A and B (Cgs-KO) with a low oral dosage of L-DOPA/benserazide (10/2.5 mg/kg). Motor performance in the rota-rod test, open field activity, and metabolic cages indicated a progressive impairment in motor coordination in these mice, and an increase in rearing behavior, which was accompanied by an increase in DA within the substantia nigra. We conclude that mild chronic L-DOPA treatment does not produce nigro-striatal toxicity that could be associated with parkinsonism, neither in control nor Cgs-KO mice. Rather, Cgs-KO mice exhibit behaviors compatible with an amphetamine-like effect, probably caused by the excess of catecholamines in the CNS.


Assuntos
Cromograninas/efeitos adversos , Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Atividade Motora/efeitos dos fármacos , Animais , Dopaminérgicos/farmacologia , Levodopa/farmacologia , Masculino , Camundongos
15.
IEEE Trans Nanobioscience ; 19(1): 11-24, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31567099

RESUMO

This review addressed erectile dysfunction, regarding pathophysiology and therapeutic strategies. The line of treatment includes phosphodiesterase type-5 inhibitors and other types of therapy like topical and stem-cell transplant. Scientific literature was assessed to investigate the impact of nanotechnology on erectile dysfunction therapy. Various nanotechnology approaches were applied, like vesicular systems, lipid-based carriers, nanocrystals, dendrimers, liquid crystalline systems and nanoemulsions. Smart nano-systems can alter the landscape of the modern pharmaceutical industry by re- investigation of pharmaceutically suboptimal but biologically active entities for treatment of erectile dysfunction which were previously considered undeveloped.


Assuntos
Disfunção Erétil/terapia , Nanomedicina/métodos , Dopaminérgicos/uso terapêutico , Terapia Genética/métodos , Humanos , Masculino , Nanopartículas/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Receptores de Melanocortina/agonistas
16.
J Med Case Rep ; 13(1): 389, 2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31874650

RESUMO

BACKGROUND: Atrial myxomas are generally considered benign neoplasms. The majority of tumors are sporadic and less than 10% are associated with an autosomal dominant condition known as the Carney complex, which is most often caused by germline mutation in the gene PRKAR1A. Whether this gene plays a role in the development of sporadic myxomas has been an area of debate, although recent studies have suggested that some fraction of sporadic tumors also carry mutations in PRKARIA. Extra-cardiac complications of atrial myxoma include dissemination of tumor to the brain; however, the dissemination of viable invasive tumor cells is exceedingly rare. CASE PRESENTATION: We present here a 48-year-old white woman who developed multiple intracranial hemorrhagic lesions secondary to tumor embolism that progressed to 'false' aneurysm formation and invasion through the vascular wall into brain parenchyma 7 months after resection of an atrial myxoma. Whole exome sequencing of her tumor revealed multiple mutations in PRKAR1A not found in her germline deoxyribonucleic acid (DNA), suggesting that the myxoma in this patient was sporadic. CONCLUSIONS: Our patient illustrates that mutations in PRKAR1A may be found in sporadic lesions. Whether the presence of this mutation affects the clinical behavior of sporadic tumors and increases risk for metastasis is not clear. Regardless, the protein kinase A pathway which is regulated by PRKAR1A represents a possible target for treatment in patients with metastatic cardiac myxomas harboring mutations in the PRKARIA gene.


Assuntos
Neoplasias Encefálicas/secundário , Complexo de Carney/diagnóstico , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Dopaminérgicos/uso terapêutico , Neoplasias Cardíacas/diagnóstico , Memantina/uso terapêutico , Mixoma/diagnóstico , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/terapia , Complexo de Carney/genética , Quimiorradioterapia , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Mutação em Linhagem Germinativa , Neoplasias Cardíacas/fisiopatologia , Neoplasias Cardíacas/terapia , Humanos , Hemorragias Intracranianas , Pessoa de Meia-Idade , Mixoma/fisiopatologia , Mixoma/terapia , Resultado do Tratamento , Sequenciamento Completo do Exoma
17.
Medicine (Baltimore) ; 98(46): e17834, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725623

RESUMO

RATIONALE: Spinocerebellar ataxia 2 (SCA2) is a genetic disease, mainly characterized by ataxia. A number of other neurological symptoms also have been described, such as Parkinsonism, cognitive dysfunction, autonomic dysfunction, even the signs of motor neuron disease and so on. Mostly, In the same family, clinical performance is the same in most cases. Here, we describe a father and his son who suffered from SCA2, but their first manifestations were different. PATIENT CONCERNS: The father exhibited progressive bradykinesia and rigidity, which resulted in the dysfunction of walking and caring himself. He hoped to relieve his symptoms by taking medicine. But the son presented with ataxia which was mild that the discomfort did not affect his daily life with none treated. DIAGNOSIS: Both of them were given SCA2 tests. Briefly, we designed primers around the CAG trinucleotide, repeated the spinal cerebellar ataxia subtype gene, performed PCR expansion, and then calculated the specific number of repetitions by capillary electrophoresis. Abnormal expansion was detected in them through SCA2 sequencing with different repeat numbers of CAG, and then they were diagnosed with SCA2 sequencing. INTERVENTIONS: The father was treated with dopaminergic drugs, but the son was not administered treatment. OUTCOMES: The father's symptoms are improved and he can take care of himself. The son has none difficulty in his daily life. LESSONS: It is rare that different individuals in the same family with SCA2 have different manifestations. The genetic testing is a crucial method to diagnose the disease of SCA2.


Assuntos
Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia , Adulto , Dopaminérgicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Ataxias Espinocerebelares/tratamento farmacológico
18.
Dialogues Clin Neurosci ; 21(3): 301-308, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31749654

RESUMO

Evidence for pharmacological remediation of cognitive deficits in three major psychiatric disorders-attention deficit- hyperactivity disorder (ADHD), schizophrenia, and depression-is reviewed. ADHD is effectively treated with the stimulant medications methylphenidate and d-amphetamine, as well as nonstimulants such as atomoxetine, implicating cognitive enhancing effects mediated by noradrenaline and dopamine. However, the precise mechanisms underlying these effects remains unclear. Cognitive deficits in schizophrenia are less effectively treated, but attempts via a variety of neurotransmitter strategies are surveyed. The possibility of treating cognitive deficits in depression via antidepressant medication (eg, selective serotonin reuptake inhibitors) and by adjunctive drug treatment has only recently received attention because of confounding, or possibly interactive, effects on mood. Prospects for future advances in this important area may need to take into account transdiagnostic perspectives on cognition (including neurodegenerative diseases) as well as improvements in neuropsychological, neurobiological, and clinical trial design approaches to cognitive enhancement.
.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Dopaminérgicos/uso terapêutico , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Resultado do Tratamento
19.
Mymensingh Med J ; 28(4): 762-766, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31599238

RESUMO

Stroke is one of the leading cause of disability worldwide. Motor function deficits due to stroke contribute to overall low quality of life. The objective was of this study is to observe functional motor outcome after stroke with low dose Levodopa therapy. This prospective follow up study was carried out in the Department of Neurology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2014 to June 2016 to see the effect of low dose of Levodopa (110mg) on motor outcome after stoke disability. Motor deficit was measured by Medical Research Council (MRC) grading and Rivermead Mobility Index (RMI) score. Two groups were selected by simple random method, consisted of both ischemic and hemorrhagic stroke. All the patients of both the groups were suffering from at least some post stroke motor disability and attended full course of physiotherapy. The group (L) received 110mg Levodopa with physiotherapy. On the other hand (NL) group received only physiotherapy. They were all followed up for four times within two months of time and were assessed for recovery of motor function. Mean age was 59.03±11.56 years in Levodopa (L) group and 57.10±12.41 years in the Non Levodopa (NL) group; Males were predominant in both groups. Ninety three (77.50%) cases had ischemic stroke and 27(22.50%) cases had hemorrhagic stroke. Most common risk factors were hypertension and smoking. No known risk factor was detected in 8 (6.67%) patients. Single or multiple risk factors were confirmed in 112 patients (93.33%). MRC score was significantly higher both in affected upper and lower limb in Levodopa group comparing non Levodopa group at 4th visit. RMI score was also significantly higher in Levodopa group comparing non Levodopa group at 4th visit. The Levodopa (L) group showed better recovery pattern than Non Levodopa (NL) group. It can be concluded that motor recovery was better with administration of a single low dose of Levodopa in combination with physiotherapy. Motor outcome was significantly higher in levodopa group than non-levodopa group.


Assuntos
Pessoas com Deficiência , Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Transtornos Motores/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Bangladesh , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida
20.
Brain ; 142(11): 3605-3620, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603493

RESUMO

Reduced levels of dopamine in Parkinson's disease contribute to changes in learning, resulting from the loss of midbrain neurons that transmit a dopaminergic teaching signal to the striatum. Dopamine medication used by patients with Parkinson's disease has previously been linked to behavioural changes during learning as well as to adjustments in value-based decision-making after learning. To date, however, little is known about the specific relationship between dopaminergic medication-driven differences during learning and subsequent changes in approach/avoidance tendencies in individual patients. Twenty-four Parkinson's disease patients ON and OFF dopaminergic medication and 24 healthy controls subjects underwent functional MRI while performing a probabilistic reinforcement learning experiment. During learning, dopaminergic medication reduced an overemphasis on negative outcomes. Medication reduced negative (but not positive) outcome learning rates, while concurrent striatal blood oxygen level-dependent responses showed reduced prediction error sensitivity. Medication-induced shifts in negative learning rates were predictive of changes in approach/avoidance choice patterns after learning, and these changes were accompanied by systematic striatal blood oxygen level-dependent response alterations. These findings elucidate the role of dopamine-driven learning differences in Parkinson's disease, and show how these changes during learning impact subsequent value-based decision-making.


Assuntos
Corpo Estriado/fisiopatologia , Dopaminérgicos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Idoso , Aprendizagem da Esquiva/efeitos dos fármacos , Simulação por Computador , Tomada de Decisões/efeitos dos fármacos , Feminino , Humanos , Aprendizagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Resultado do Tratamento
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