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1.
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
2.
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
3.
Adv Pharmacol ; 84: 187-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31229171

RESUMO

Two types of drugs have been extensively investigated for the treatment of restless legs syndrome (RLS)/Willis-Ekbom disease (WED): dopamine agonists and α2δ ligands to the α2δ subunit of calcium channels. Comparative studies show that both classes of drugs are similarly effective in treating RLS symptoms over the short- and long-term. While dopamine agonists are more effective in treating periodic limb movements (PLMs), α2δ ligands are more effective in consolidating sleep. However, given the fact that dopamine agonists cause high rates of augmentation of symptoms, recent international guidelines recommend that whenever possible the initial treatment of choice should be an α2δ ligand. In fact, the most effective preventive strategy involves not using dopaminergic agents unless absolutely necessary. Indeed, should dopaminergic treatment be needed to handle the symptoms effectively, then it is recommended that the dopaminergic load be reduced by using the lowest effective dose for the shortest possible period of time. However, it must be taken into account that the only α2δ ligand approved for RLS/WED is gabapentin enacarbil, which is not yet available in Europe. Furthermore, recent studies have also reported on the efficacy of opioids as a second-line treatment of RLS/WED, following treatment failure with dopamine agonists. Recent guidelines have taken these new data into account and highlight that a low dose of an opioid (prolonged-release oxycodone or methadone) may be considered in patients with very severe augmentation of symptoms. Alternative non-dopaminergic treatment concepts based on glutamatergic and adenosinergic mechanisms are currently in development, and are likely to provide encouraging therapeutic alternatives.


Assuntos
Dopaminérgicos/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Humanos , Ligantes , Síndrome das Pernas Inquietas/fisiopatologia , Sono/fisiologia
4.
Eur J Cancer Care (Engl) ; 28(3): e13088, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31090162

RESUMO

INTRODUCTION: Many patients with brain cancer experience cognitive problems. In this narrative review, we comprehensively evaluated empirical studies on various intervention approaches for cognitive problems in these patients. METHODS: Intervention studies that reported effects on cognitive functioning (either objectively tested or subjectively reported) in adult patients with primary and/or secondary brain tumours were identified through online searches in PubMed (MEDLINE) and Web of Science up to 13 March 2019. RESULTS: Of the 364 identified records, 10 pharmacological (including five randomised placebo-controlled trials), 10 cognitive rehabilitation (including five [pilot] RCTs) and two multiple-group exercise studies matched the inclusion criteria. Seventeen of 22 studies had final sample sizes smaller than 40. Several cognitive rehabilitation studies and some pharmacological approaches (donepezil and memantine) showed (at least partial) benefits for cognitive problems in adults with brain cancer. The effects of other pharmacological and exercise interventions were inconclusive and/or preliminary. CONCLUSION: Overall, drawing firm conclusions is complicated due to various methodological shortcomings, including the absence of a (placebo) control group and small sample sizes. Promising effects have been reported for cognitive rehabilitation and some pharmacological approaches. Suggestions for more thorough research with respect to the various approaches are provided.


Assuntos
Neoplasias Encefálicas/reabilitação , Estimulantes do Sistema Nervoso Central/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Disfunção Cognitiva/reabilitação , Remediação Cognitiva , Dopaminérgicos/uso terapêutico , Exercício , Neoplasias Encefálicas/psicologia , Cognição , Disfunção Cognitiva/psicologia , Donepezila/uso terapêutico , Humanos , Memantina/uso terapêutico , Extratos Vegetais/uso terapêutico
8.
Gait Posture ; 70: 98-103, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30836253

RESUMO

BACKGROUND: Studies have shown that dual-task standing balance in Parkinson's disease (PD) is significantly diminished. Additionally, it is well accepted that dopaminergic medication improves dynamic balance (Berg Balance Scale, mini-BESTest), but standing balance (force platform posturography) may suffer. What remains unknown is how dopaminergic medication influences standing balance automaticity in PD. RESEARCH QUESTION: Does dopaminergic medication improve standing balance automaticity during a phoneme monitoring dual-task in PD? METHODS: This was a cross-sectional study. Sixteen subjects with PD completed single- and dual-task standing with eyes open and eyes closed for 3 min each in off and on medication states. 95% confidence ellipse area, anterior-posterior sway velocity, medial-lateral sway velocity, and integrated time to boundary were calculated. Data were analyzed with a repeated measures ANOVA. RESULTS: Dopaminergic medication significantly increased ellipse area (p = 0.002) and decreased the performance on the secondary task (p = 0.004). Different eyes conditions (open vs. closed) significantly increased both sway velocities (anterior-posterior = p < 0.001, medial-lateral = p < 0.001), and increased integrated time to boundary (p < 0.001). There were also task by eyes condition interaction effects for anterior-posterior velocity and integrated time to boundary (p = 0.015 and p = 0.009, respectively). Increases in sway velocity and integrated time to boundary seen in the eyes condition and interaction effects are traditionally interpreted as poorer balance performance. However, in the context of stability/maneuverability tradeoff, the changes may indicate an increase in freedom of movement instead of a decrease in stability. SIGNIFICANCE: The data did not support a medication-induced improvement in automaticity, as measured by significant medication by task interactions. An alternate interpretation for medication-induced balance changes in PD includes an increase in maneuverability without sacrificing stability after taking dopaminergic medication.


Assuntos
Dopaminérgicos/farmacologia , Comportamento Multitarefa/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Equilíbrio Postural/efeitos dos fármacos , Idoso , Estudos Transversais , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/psicologia , Resultado do Tratamento
9.
Arq Neuropsiquiatr ; 77(1): 47-54, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30758442

RESUMO

Parkinson's disease (PD) and restless legs syndrome/Willis-Ekbom disorder (RLS/WED) are relatively common diseases in the realm of movement disorders. The fact that both may, as expected, co-occur and typically share a similar remarkable response to dopaminergic treatment raised the interest in exploration of additional shared features that throughout the years cruised fields as diverse as phenomenology, epidemiology, genetics, pathology, and clinical studies. In this review, we describe and critically examine the evidence and biases of a conceivable overlap of these two disorders, trying to shed light onto two main sources of confusion: (1) are PD and RLS/WED reciprocal risk factors? and (2) what are the main mimics of RLS/WED in PD?


Assuntos
Dopaminérgicos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Síndrome das Pernas Inquietas/tratamento farmacológico , Síndrome das Pernas Inquietas/fisiopatologia , Diagnóstico Diferencial , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/genética , Fatores de Risco , Resultado do Tratamento
10.
Neurochem Int ; 125: 35-46, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30716356

RESUMO

Dopamine D2 receptors (D2Rs) mediate many of the actions of dopamine in the striatum, ranging from movement to the effortful pursuit of reward. Yet despite significant advances in linking D2Rs to striatal functions with pharmacological and genetic strategies in animals, how dopamine orchestrates its myriad actions on different cell populations -each expressing D2Rs- remains unclear. Furthermore, brain imaging and genetic studies in humans have consistently associated striatal D2R alterations with various neurological and neuropsychiatric disorders, but how and which D2Rs are involved in each case is poorly understood. Therefore, a critical first step is to engage in a refined and systematic investigation of the impact of D2R function on specific striatal cells, circuits, and behaviors. Here, I will review recent efforts, primarily in animal models, aimed at unlocking the complex and heterogeneous roles of D2Rs in striatum.


Assuntos
Corpo Estriado/metabolismo , Transtornos Mentais/metabolismo , Obesidade/metabolismo , Receptores de Dopamina D2/fisiologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Animais , Corpo Estriado/efeitos dos fármacos , Dopaminérgicos/metabolismo , Dopaminérgicos/farmacologia , Dopaminérgicos/uso terapêutico , Humanos , Transtornos Mentais/tratamento farmacológico , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/metabolismo , Obesidade/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico
11.
J Neurol ; 266(5): 1141-1152, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30783749

RESUMO

INTRODUCTION: We sought to analyze the blood pressure (BP) circadian rhythm in Parkinson's disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) and to evaluate the effect of vasoactive and dopaminergic medications on BP fluctuations during activities of daily living. METHODS: We analyzed data from patients with PD (n = 72), MSA (n = 18), and PAF (n = 17) evaluated with 24-h ambulatory BP monitoring (ABPM) at our Center between 1996 and 2015. Comparisons between groups were performed according to (a) clinical diagnosis and (b) pharmacological treatment. ABPM parameters included 24-h BP variability, BP load, nocturnal dipping, and awakening hypotension. RESULTS: The average BP was 121 ± 14/72 ± 8 mmHg during daytime and 133 ± 20/76 ± 13 mmHg during nighttime (p < 0.01), with BP load of 24 ± 22/15 ± 16% (daytime) vs. 61 ± 36/52 ± 36% (nighttime) (p < 0.01). In-office BP measurements were consistent with OH in 95 patients (89%) and SH in 63 (59%). ABPM demonstrated increased BP variability in 67 patients (63%), awakening hypotension in 63 (59%), "reverse dipping" in 85 (79.4%), "reduced dipping" in 13 (12.1%), and "normal dipping" in 9 (8.4%). No differences were observed between PD, MSA, and PAF, but a sub-analysis of PD patients revealed two distinct patterns of BP alterations. No significant differences were observed in relation to the use of vasoactive or dopaminergic medications. CONCLUSION: Regardless of the neurological diagnosis and pharmacological treatment, patients with alpha-synucleinopathies showed a BP circadian rhythm characterized by increased BP variability, reverse dipping, increased BP load, and awakening hypotension.


Assuntos
Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Doença de Parkinson/fisiopatologia , Insuficiência Autonômica Pura/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Dopaminérgicos/uso terapêutico , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Atrofia de Múltiplos Sistemas/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Insuficiência Autonômica Pura/tratamento farmacológico , Estudos Retrospectivos , Estatísticas não Paramétricas , Manobra de Valsalva , Vasoconstritores/uso terapêutico
12.
Gait Posture ; 69: 66-78, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30677709

RESUMO

BACKGROUND: Analysis of sensorimotor synergies has been greatly advanced by the Uncontrolled Manifold (UCM) approach. The UCM method is based on partitioning inter-trial variance displayed by elemental variables into 'good' (VUCM) and 'bad' (VORT) variability that, respectively, indicate maintenance or loss of task stability. In clinical populations, these indices can be used to investigate the strength, flexibility, stereotypy and agility of synergistic control. RESEARCH QUESTION: How are synergies affected by neurological impairment in adults? Specifically, this study aimed to determine i) the impact of pathology on VUCM, VORT, and their ratio (synergy index); ii) the relationship between synergy indices and functional performance; iii) changes in anticipatory synergy adjustments (ASAs); and iv) the effects of interventions on synergies. METHODS: Systematic review of UCM studies on adults with neurological impairment. RESULTS: Most of the 17 studies had moderate to high quality scores in the adapted Critical Review Form and the UCM reporting quality checklist developed for this review. i) Most of the studies found reduced synergy indices for patients with Parkinson's disease (PD), olivo-ponto-cerebellar atrophy, multiple sclerosis and spinocerebellar degeneration, with variable levels of change in VUCM and VORT. Reduction in synergy indices was not as consistent for stroke, in three out of six studies it was unchanged. ii) Five of seven studies found no significant correlations between scores on motor function scales and UCM indices. iii) Seven studies consistently reported ASAs that are smaller in magnitude, delayed, or both, for patients compared to healthy controls. iv) Two studies reported increased synergy indices, either via increase in VUCM or decrease in VORT, after dopaminergic drugs for patients with PD. There were similar synergy indices but improved ASAs after deep brain stimulation for patients with PD. SIGNIFICANCE: UCM can provide reliable and sensitive indicators of altered synergistic control in adults with neurological impairment.


Assuntos
Estimulação Encefálica Profunda/métodos , Dopaminérgicos/uso terapêutico , Doença de Parkinson/fisiopatologia , Desempenho Psicomotor/fisiologia , Humanos , Doença de Parkinson/terapia
13.
Psychosomatics ; 60(2): 139-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30665668

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is an increasingly common cause of behavioral and emotional dysregulation among hospitalized patients. While consultation-liaison psychiatrists are often called to help manage these behaviors, acute pharmacological management guidelines are limited. OBJECTIVE: Conduct a systematic review to determine which pharmacological measures are supported by the literature for targeting agitation and aggression in the acute time period following a TBI. METHODS: In a systematic review of MEDLINE, Embase, PsycInfo, ClinicalTrials.gov and the Cochrane Library, we identified and then analyzed publications that investigated the pharmacological management of behavioral and emotional dysregulation following a TBI during the acute time period following injury. RESULTS: There were a limited number of high quality studies that met our inclusion criteria, including only five randomized controlled trials. The majority of the literature identified consisted of case reports or case series. Trends identified in the literature reviewed suggested that amantadine, propranolol, and anti-epileptics were the best supported medications to consider. For many medication classes, the time of medication initiation and duration of treatment, relative to the time of injury, may impact the effect observed. CONCLUSIONS: The pharmacological management of agitated patients immediately following a TBI is still an area of much-needed research, as there is limited data-driven guidance in the literature.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Agressão/psicologia , Amantadina/uso terapêutico , Anticonvulsivantes/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Dopaminérgicos/uso terapêutico , Comportamento Problema/psicologia , Propranolol/uso terapêutico , Doença Aguda , Lesões Encefálicas Traumáticas/psicologia , Humanos , Guias de Prática Clínica como Assunto
14.
Clin Pharmacol Ther ; 105(5): 1106-1120, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30661251

RESUMO

The progressive neurodegenerative process in Parkinson's disease (PD) is not restricted to dopaminergic midbrain neurons but involves the entire nervous system. In this review, we outline established treatment options at different disease stages and address new therapeutic approaches. These include, based on recent advances in the understanding of the pathophysiology of PD, genetic and disease-modifying approaches to reduce abnormal accumulation and aggregation of alpha-synuclein (aSYN), mitochondrial dysfunction, and dysfunction of lysosomal proteins. Moreover, we highlight clinical trials to reduce neuroinflammation and increase neurorestoration.


Assuntos
Antiparkinsonianos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Antiparkinsonianos/farmacologia , Dopaminérgicos/uso terapêutico , Humanos , Fármacos Neuroprotetores , Doença de Parkinson/genética
15.
Brain ; 142(3): 719-732, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30689734

RESUMO

Disorders of motivation, such as apathy, are common in Parkinson's disease, and a key feature of such disorders is a greater aversion to effort. In humans, the experience of cognitive effort is ubiquitous, and cognitive apathy has traditionally been considered distinct and separable from other subtypes. Surprisingly, however, the neurobiology of cognitive motivation is poorly understood. In particular, although dopamine has a well-characterized role in incentivizing physically effortful behaviour, a critical, unresolved issue is whether its facilitatory role generalizes to other domains. Here, we asked how dopamine modulates the willingness of patients with Parkinson's disease to invest cognitive effort in return for reward. We tested 20 patients with idiopathic Parkinson's disease across two counterbalanced sessions-ON and OFF their usual dopaminergic medication-and compared their performance to 20 healthy age-matched controls. We applied a novel task in which we manipulated cognitive effort as the number of rapid serial visual presentation streams to which participants had to attend. After training participants to ceiling performance, we then asked them to choose between a low-effort/low-reward baseline option, and a higher-effort/higher-reward offer. Computational models of choice behaviour revealed four key results. First, patients OFF medication were significantly less cognitively motivated than controls, as manifest by steeper cognitive effort discounting functions in the former group. Second, dopaminergic therapy improved this deficit, such that choices in patients ON medication were indistinguishable from controls. Third, differences in motivation were also accompanied by independent changes in the stochasticity of individuals' decisions, such that dopamine reduced the variability in choice behaviour. Finally, choices on our task correlated uniquely with the subscale of the Dimensional Apathy Scale that specifically indexes cognitive motivation, which suggests a close relationship between our laboratory measure of cognitive effort discounting and subjective reports of day-to-day cognitive apathy. Importantly, participants' choices were not confounded by temporal discounting, probability discounting, physical demand, or varying task performance. These results are the first to reveal the central role of dopamine in overcoming cognitive effort costs. They provide an insight into the computational mechanisms underlying cognitive apathy in Parkinson's disease, and demonstrate its amenability to dopaminergic therapy. More broadly, they offer important empirical support for prominent frameworks proposing a domain-general role for dopamine in value-based decision-making, and provide a critical link between dopamine and multidimensional theories of apathy.


Assuntos
Cognição/efeitos dos fármacos , Dopamina/farmacologia , Doença de Parkinson/tratamento farmacológico , Idoso , Apatia , Simulação por Computador , Tomada de Decisões , Dopamina/metabolismo , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação/efeitos dos fármacos , Esforço Físico , Recompensa
16.
Curr Diabetes Rev ; 15(2): 93-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29692257

RESUMO

BACKGROUND: For more than three decades, it has been known that manipulation of dopaminergic system could affect glucose homesotasis in experimental animals. The notion that glucose homeostasis in human might be influenced by dopaminergic drugs has attracted a great deal of attention in the past two decades. In spite of rapid advancements in revealing involvement of dopaminergic neurotransmission in insulin release, glucose up-take and pancreatic beta cell function in general through centrally and peripherally controlled mechanisms, there are discrepancies among observations on experimental animals and human subjects. CONCLUSION: With the expansion of pharmacotherapy in psychotic conditions, depression and endocrine abnormalities along with a sharp increase in prevalence of type two diabetes and disturbances of glucose homeostasis as a major risk factor for many cardiovascular complications and associated mortalities; it seems a critical analysis of recent investigations on drugs which act as agonists or antagonists of dopaminergic receptors in various tissues and organs may provide better insight into how safe and efficient these medicines could be prescribed. Furthermore, the other main objective of present review is to compare clinical data on significance of changes in blood glucose and insulin levels during short term and after long term treatment with these agents. This in turn would be beneficial for determining adequate strategies to combat or to avoid adverse effects associated with dopaminergic drug therapy.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Dopaminérgicos/uso terapêutico , Glucose/metabolismo , Insulina/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dopaminérgicos/efeitos adversos , Homeostase , Humanos , Células Secretoras de Insulina/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo
17.
Brain Dev ; 41(3): 250-256, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30352709

RESUMO

BACKGROUND: Molecular technologies are expanding our knowledge about genetic variability underlying early-onset non-progressive choreic syndromes. Focusing on NKX2-1-related chorea, the clinical phenotype and sleep related disorders have been only partially characterized. METHODS: We propose a retrospective and longitudinal observational study in 7 patients with non-progressive chorea due to NKX2-1 mutations. In all subjects sleep and awake EEG, brain MRI with study of pituitary gland, chest X-rays, endocrinological investigations were performed. Movement disorders, pattern of sleep and related disorders were investigated using structured clinical evaluation and several validated questionnaires. RESULTS: In patients carrying NKX2-1 mutations, chorea was mainly distributed in the upper limbs and tended to improve with age. All patients presented clinical or subclinical hypothyroidism and delayed motor milestones. Three subjects had symptoms consistent with Restless Legs Syndrome (RLS) that improved with Levodopa. CONCLUSIONS: Patients with NKX2-1 gene mutations should be investigated for RLS, which, similarly to chorea, can sometimes be ameliorated by Levodopa.


Assuntos
Coreia/complicações , Coreia/genética , Mutação/genética , Síndrome das Pernas Inquietas/etiologia , Fator Nuclear 1 de Tireoide/genética , Adulto , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Coreia/diagnóstico por imagem , Estudos de Coortes , Dopaminérgicos/uso terapêutico , Saúde da Família , Feminino , Humanos , Levodopa/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Hipófise/diagnóstico por imagem , Síndrome das Pernas Inquietas/diagnóstico por imagem , Síndrome das Pernas Inquietas/tratamento farmacológico
18.
Mov Disord ; 34(1): 114-123, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30311259

RESUMO

BACKGROUND: Restless legs syndrome is a sensorimotor neurological disorder of the limbs that impairs quality of life and disturbs sleep. However, there has been progress in understanding the disease involving the dopaminergic system as well as iron metabolism. The exact pathophysiological mechanisms of restless legs syndrome remain elusive. We tried to elucidate the underlying mechanisms in iron metabolism in restless legs syndrome subjects on a systemic, cellular, and mitochondrial level. METHODS: We conducted a study prospectively recruiting 168 restless legs syndrome patients and 119 age-matched healthy controls focusing on iron metabolism using human monocytes as surrogates. RESULTS: Evaluation of systemic iron metabolism parameters in the circulation showed no significant difference between patients and controls. We observed a significant reduction in mRNA levels of heme oxygenase 1 and mitochondrial iron genes like mitoferrin 1 and 2 in monocytes isolated from restless legs syndrome patients, indicating mitochondrial iron deficiency. Interestingly, we also observed reduced expression of iron regulatory protein 2 along with impaired activity of mitochondrial aconitase and reduced mitochondrial superoxide formation in restless legs syndrome subjects. Along this line, patients had reduced mitochondrial respiratory capacity that improved in restless legs syndrome subjects under treatment with dopaminergic drugs compared with untreated patients. CONCLUSIONS: Our data suggest that restless legs syndrome is linked to mitochondrial iron deficiency and associated impairment of mitochondrial function. This is partly corrected by treatment with dopaminergic drugs compared with untreated patients, which may be linked to an effect of dopamine on cellular iron homeostasis. © 2018 International Parkinson and Movement Disorder Society.


Assuntos
Dopaminérgicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Homeostase/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Síndrome das Pernas Inquietas/tratamento farmacológico , Anemia Ferropriva/tratamento farmacológico , Feminino , Humanos , Masculino , Mitocôndrias/metabolismo , Qualidade de Vida
19.
Neurology ; 92(2): e148-e160, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30541866

RESUMO

OBJECTIVE: To determine the time course of hazard for motor and nonmotor milestones of Parkinson disease (PD) in the long term and to investigate whether risk scales nonlinearly with time is instrumental in identifying changes in pathological processes and evaluating disease-modifying therapies in PD. METHODS: Outpatients with PD at the Lyon University Movement Disorders Center were evaluated for 7 clinical milestones in this retrospective cohort study, encompassing 4 domains of PD progression: (1) motor (motor fluctuations, dyskinesias); (2) axial (postural instability and falls, freezing of gait); (3) neuropsychiatric (impulse control disorders, hallucinations); and (4) cognitive (dementia) complications. For each complication, we estimated the outcome-specific hazard using parsimonious smooth parametric Poisson regression models allowing for nonlinear scaling over disease duration, age at diagnosis, current age, and their interaction. RESULTS: A total of 1,232 patients with PD experienced 1,527 disease-related complications in up to 12 years of follow-up. Specific to each complication, hazard rates increased dramatically starting from diagnosis and were highest for motor fluctuations and lowest for dementia up to 6 years after diagnosis in patients aged 65 years at diagnosis. Nonlinear patterns indicated dramatic changes in the course of PD after 5 years and predicted more severe axial prognosis after 70 years and for motor fluctuations, dyskinesias, and impulse control disorders before 60 years at diagnosis. CONCLUSION: Time course of motor and nonmotor milestones in PD is determined by disease duration and age at diagnosis in nonlinear patterns and their interaction. This indicates disease- and age-specific thresholds across the multiple neurodegenerative processes accumulating in PD at different paces.


Assuntos
Envelhecimento , Transtornos Cognitivos/etiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Discinesias/etiologia , Transtornos Neurológicos da Marcha/etiologia , Doença de Parkinson/complicações , Idoso , Estudos de Coortes , Progressão da Doença , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Análise de Regressão , Índice de Gravidade de Doença , Fatores de Tempo
20.
Neurol Sci ; 40(2): 311-317, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30415448

RESUMO

INTRODUCTION: Patients with Parkinson's disease (PD) present a variety of non-motor symptoms. However, it remains unclear whether dopamine depletion is related to non-motor symptoms, and which non-motor symptoms are significantly dependent on dopaminergic deficit. METHODS: Forty-one patients with PD who underwent positron emission tomography imaging of dopamine transporters (DATs) were recruited for this study. The striatum was divided into 12 subregions, and DAT activity, as striatal dopaminergic concentration, was calculated in each subregion. In addition to measuring motor symptoms using the Unified Parkinson's Disease Rating Scale-part III (UPDRS-III), various non-motor symptoms were assessed using the Montreal cognitive assessment, frontal assessment battery, Beck depression inventory (BDI), Beck anxiety inventory, PD sleep scale (PDSS), PD fatigue scale, and non-motor symptoms scale (NMSS) for PD. RESULTS: For simple linear regression analyses, dopaminergic depletion in all striatal subregions was negatively correlated with the UPDRS-III score. The most relevant non-motor symptom assessment related to dopaminergic loss in the 12 subregions was NMSS, followed by BDI and PDSS. However, following multiple linear regression analyses, dopaminergic depletion in the 12 striatal subregions was not related with any of the non-motor symptoms. Conversely, dopaminergic deficit in the right anterior and posterior putamen was associated with the UPDRS-III score. CONCLUSIONS: Striatal dopaminergic depletion was not significantly correlated with any of the various non-motor symptoms in PD. Our findings suggest that non-dopaminergic systems are significantly implicated in the pathogenesis of non-motor symptoms in patients with PD.


Assuntos
Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons , Idoso , Antiparkinsonianos/uso terapêutico , Mapeamento Encefálico , Dopamina/deficiência , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Escalas de Graduação Psiquiátrica , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Índice de Gravidade de Doença , Tropanos
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