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1.
J Neural Transm (Vienna) ; 123(12): 1415-1421, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27586162

RESUMO

In the motor system, botulinum toxin type A (BoNT/A) actions were classically attributed to its well-known peripheral anticholinergic actions in neuromuscular junctions. However, the enzymatic activity of BoNT/A, assessed by the detection of cleaved synaptosomal-associated protein 25 (SNAP-25), was recently detected in motor and sensory regions of the brainstem and spinal cord after toxin peripheral injection in rodents. In sensory regions, the function of BoNT/A activity is associated with its antinociceptive effects, while in motor regions we only know that BoNT/A activity is present. Is it possible that BoNT/A presence in central motor nuclei is without any function? In this brief review, we analyze this question. Limited data available in the literature warrant further investigations of BoNT/A actions in motor nervous system.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Sistema Nervoso , Animais , Toxinas Botulínicas Tipo A/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , Sistema Nervoso/citologia , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/metabolismo , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia
2.
Eur J Neurol ; 23(4): 772-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26826067

RESUMO

BACKGROUND AND PURPOSE: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. METHODS: A survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. RESULTS: Lack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. CONCLUSIONS: Internationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.


Assuntos
Distúrbios Distônicos/terapia , União Europeia/estatística & dados numéricos , Clínicos Gerais/estatística & dados numéricos , Neurologia/estatística & dados numéricos , Distúrbios Distônicos/tratamento farmacológico , Clínicos Gerais/educação , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Humanos , Neurologia/educação
3.
Eur J Neurol ; 20(1): 16-34, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23279440

RESUMO

BACKGROUND: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. METHODS: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. RESULTS: For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [(123) I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. CONCLUSIONS: The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre-symptomatic phase of the disease.


Assuntos
Guias como Assunto , Doença de Parkinson/diagnóstico , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/etiologia , Encéfalo/patologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Bases de Dados Factuais/estatística & dados numéricos , Diagnóstico por Imagem , Europa (Continente) , Testes Genéticos , Humanos , Neurofisiologia , Testes Neuropsicológicos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Doença de Parkinson/complicações , Fatores de Risco , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia
4.
Eur J Neurol ; 15(2): 128-33, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18217883

RESUMO

Whilst the association between dementia and poorer health-related quality of life (Hr-QoL) in Parkinson's disease (PD) has been well established, we aimed to explore the relationship between cognitive performance and Hr-QoL in PD without dementia. Consecutive PD patients (n = 124, 54% men, age 60.4 +/- 10.3 years) judged as non-demented based on DSM-IV criteria and Mini Mental State Examination, free of other neurodegenerative diseases or psychotic difficulties and antipsychotic/antidepressive/anxyolitic treatment were assessed in a battery of neuropsychological tests. We used Parkinson's disease questionnaire (PDQ-39) to asses Hr-QoL and Beck's Depression Inventory (BDI) to quantify depression. In the univariate analysis, better performance in each of the tests evaluating visual attention/memory or visuospatial and executive functions was associated with better Hr-QoL. In multivariate analysis [adjustment for BDI score, PD severity and duration, l-dopa dose, age, sex, education, employment status and early PD onset (<50 years of age)] in which these tests were either represented by a common variable identified in a principal components analysis or were considered individually, better cognitive performance was independently associated with better Hr-QoL. The association was conditional on the level of depression, i.e., apparent only in patients with low(er) BDI scores. Cognitive performance appears associated with Hr-QoL even in non-demented PD patients.


Assuntos
Cognição , Nível de Saúde , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Qualidade de Vida , Idoso , Estudos Transversais , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico , Análise de Componente Principal , Escalas de Graduação Psiquiátrica , Análise de Regressão , Inquéritos e Questionários
5.
J Neurol ; 254(12): 1676-83, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17990062

RESUMO

BACKGROUND: Animal data and postmortem studies suggest a role of oxidative stress in the Huntington's disease (HD), but in vivo human studies have been scarce. AIM: To assess the presence of oxidative stress in HD patients and its occurrence relative to clinical symptoms. METHODS: Oxidative stress markers were determined in plasma of HD patients (n = 19), asymptomatic HD gene carriers (with > 38 CAG repeats) (n = 11) and their respective sex and agematched healthy controls (n = 47 and n = 22) in a cross-sectional study. RESULTS: With adjustment for age and sex, HD patients had higher plasma lipid peroxidation (LP) levels (ratio 1.20, 95% CI 1.09 to 1.32, p < 0.001) and lower reduced glutathione (GSH) levels (ratio 0.72, CI 0.55 to 0.94, p = 0.011) than their age and sex-matched controls. Although considerably younger, HD gene carriers did not differ from HD patients regarding LP and GSH levels, and had higher plasma LP (ratio 1.16, CI 1.02 to 1.32, p = 0.016) and lower GSH than their matched controls (ratio 0.73, CI 0.5 to 1.05). They had higher LP (ratio 1.18, CI 1.02 to 1.34, p = 0.019) and lower GSH (ratio 0.75, CI 0.51 to 1.11) than the healthy subjects matched to HD patients. CONCLUSIONS: Oxidative stress is more pronounced in HD patients and asymptomatic HD gene carriers than in healthy subjects. Differences in plasma LP and GSH are in line with the brain findings in animal models of HD. Data suggest that oxidative stress occurs before the onset of the HD symptoms.


Assuntos
Doença de Huntington/sangue , Doença de Huntington/genética , Lipídeos/sangue , Estresse Oxidativo/fisiologia , Plasma/metabolismo , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Glutationa Peroxidase/sangue , Humanos , Doença de Huntington/fisiopatologia , Peroxidação de Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Estatísticas não Paramétricas , Expansão das Repetições de Trinucleotídeos/genética , Comportamento Verbal/fisiologia
6.
Prog Neuropsychopharmacol Biol Psychiatry ; 31(2): 399-402, 2007 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-17126974

RESUMO

Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment.


Assuntos
Antipsicóticos/uso terapêutico , Flufenazina/uso terapêutico , Hidrocortisona/sangue , Rigidez Muscular/induzido quimicamente , Prolactina/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Análise de Variância , Benzodiazepinas/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Olanzapina , Esquizofrenia/sangue , Esquizofrenia/fisiopatologia
7.
Eur J Neurol ; 14(2): 194-8, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17250729

RESUMO

Assessment of quality of life (QoL) has become an important measure in Parkinson's disease (PD) healthcare as a part of the efforts to evaluate the 'total burden' of the illness, and not only the motor disabilities. By analogy with some other diseases, we aimed to investigate potential urban-rural disparities in QoL in PD patients. A total of 111 consecutive PD patients were assessed for QoL using a specific 39-item version of PD quality of life questionnaire (PDQ-39) in a cross-sectional study involving two centers in Croatia. Rural life setting (adjustment for center, age, sex, levodopa dose, disease duration and severity, education, employment status and number of household co-members) was an independent negative predictor of QoL: rural patients had significantly (P < 0.05) worse PDQ-39 Summary Index Score and most of the PDQ-39 subscale scores (cognition, social support, stigma, emotional wellbeing and mobility score, and communication and activity of daily living scores with borderline significance) than their urban counterparts. Socioeconomic background should be considered in attempts to achieve the best management of PD patients' needs.


Assuntos
Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Qualidade de Vida , População Rural , Idoso , Croácia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , População Urbana
8.
Eur J Neurol ; 13 Suppl 4: 35-40, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17112348

RESUMO

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Animais , Formação de Anticorpos/efeitos dos fármacos , Blefaroptose/induzido quimicamente , Blefarospasmo/tratamento farmacológico , Transtornos de Deglutição/induzido quimicamente , Esquema de Medicação , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Humanos , Placa Motora/efeitos dos fármacos , Placa Motora/patologia , Transtornos dos Movimentos/tratamento farmacológico , Náusea/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Biol Psychiatry ; 48(7): 706-9, 2000 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-11032983

RESUMO

BACKGROUND: Schizophrenia is a complex genetic disorder with no clear pattern of inheritance. Epigenetic modification of genes may thus play a role in its transmission. METHODS: In our study, 439 families with at least two ill siblings with schizophrenia (208 with unilineal transmission) were examined for evidence of a parent-of-origin effect (e.g., evidence of parental imprinting on the familial transmission of schizophrenia). RESULTS: No significant difference in the prevalence of maternal compared with paternal transmission was found. In addition, affected male subjects did not differ from affected female subjects in the proportion of their offspring diagnosed with schizophrenia. CONCLUSIONS: Although the transmission of schizophrenia may be influenced by epigenetic events, our study fails to find evidence that one epigenetic mechanism, a parent-of-origin imprinting effect, determines whether an individual expresses the illness.


Assuntos
Esquizofrenia/genética , Adulto , Feminino , Expressão Gênica/fisiologia , Predisposição Genética para Doença/genética , Impressão Genômica/genética , Humanos , Masculino , Fenótipo , Esquizofrenia/diagnóstico
10.
Neuroscience ; 82(4): 993-7, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9466423

RESUMO

Histamine is known to be a neurotransmitter in the brain, but it has not been clearly implicated in major diseases. All histaminergic neurons reside in the posterior hypothalamus and innervate most brain areas, which is compatible with the concept that histamine is involved in general central regulatory mechanisms. A sensitive high-performance liquid chromatographic fluorimetric method was used to measure histamine contents in post mortem Alzheimer brains and age-matched controls. The cellular storage sites and distribution of histaminergic nerve fibers were examined with a specific immunohistochemical method. The histamine content was significantly reduced in the hypothalamus (42% of control value), hippocampus (43%) and temporal cortex (53%) of Alzheimer brains. Differences in other cortical areas, putamen and substantia nigra were not significant. Histamine-containing nerve fibers were found in the hippocampus, parahippocampal gyrus and subiculum of both Alzheimer brains and controls. No histamine-containing mast cells were seen in these temporal structures. Histamine in the human temporal lobe is stored in nerve fibers originating from the posterior hypothalamus, and not in mast cells. Decrease in brain histamine may contribute to the cognitive decline in Alzheimer's disease directly or through the cholinergic system. Development of drugs that penetrate the blood brain barrier and increase histaminergic activity might be beneficial in Alzheimer's disease.


Assuntos
Doença de Alzheimer/metabolismo , Química Encefálica/fisiologia , Histamina/fisiologia , Neurônios/fisiologia , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Feminino , Fluorometria , Humanos , Masculino , Mastócitos/metabolismo , Pessoa de Meia-Idade , Fibras Nervosas/metabolismo
11.
Brain Res ; 443(1-2): 199-203, 1988 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-2451990

RESUMO

The content of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) was analysed in 71 human spinal cords obtained post-mortem. The highest content of 5-HT, 5-HIAA and NE was found in the lumbar enlargement of the spinal cord. 5-HT and 5-HIAA content increased from fetal to adult spinal cord whereas the content of NE decreased. Characteristic segmental distribution of measured monoamines was present in adult spinal cord only. In two patients spinal cord lesion led to the reduction in spinal cord content of 5-HT, 5-HIAA and NE and loss of characteristic segmental distribution of these substances. These results are in general agreement with observations on spinal cord of different animal species.


Assuntos
Norepinefrina/análise , Serotonina/análise , Medula Espinal/análise , Adulto , Envelhecimento , Feminino , Humanos , Ácido Hidroxi-Indolacético/análise , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Medula Espinal/crescimento & desenvolvimento
12.
Life Sci ; 31(23): 2571-5, 1982 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-7154852

RESUMO

Specific dopaminergic recognition sites were identified in membranes prepared from rat vas deferens with the ligand (3H)-haloperidol. Specific binding, defined as the difference of (3H)-haloperidol binding in the presence or absence of an excess of unlabelled haloperidol (100 microM), was saturable and a Scatchard analysis of the data revealed a Kd = 21 nM and a Bmax = 74 fmol/mg prot. (+)-Butaclamol was several times more active in displacing (3H)-haloperidol from binding sites than its pharmacologically inactive enantiomer, (-)-butaclamol, demonstrating stereospecificity of binding. Dopamine displaced 50% of (3H)-haloperidol binding at a concentration of approximately 10 microM, while norepinephrine, epinephrine and serotonin were practically ineffective at this concentration. Our results support the notion that there are dopaminergic receptors in the rat vas deferens. We speculate that some of the known effects of dopamine and dopaminergic drugs on sexual behavior may be mediated peripherally and not solely via the CNS as is usually assumed.


Assuntos
Receptores Dopaminérgicos/análise , Ducto Deferente/metabolismo , Animais , Ligação Competitiva , Membrana Celular/metabolismo , Dopamina/metabolismo , Haloperidol/metabolismo , Masculino , Ratos , Ratos Endogâmicos
13.
Clin Neuropharmacol ; 19(2): 148-56, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8777768

RESUMO

A new computerized method is described for measuring parkinsonian rigidity with an elbow device. We present data from 127 subjects (103 controls and 24 parkinsonian patients) to show the clinical utility of the method. The instrumental quantification of rigidity correlates highly with clinical ratings of parkinsonian rigidity. The test-retest repeatability was excellent. In parkinsonian patients versus normal controls, significantly higher values of measured rigidity were observed. Moreover, activation procedure significantly increases rigidity only in parkinsonian patients. Activated rigidity in control subjects is lower than basal values. The procedure was sensitive to increased rigidity in parkinsonian patients during 3 days' drug holiday. Contrary to previous reports, levodopa therapy reduced both basal and activated rigidity in parkinsonian patients. This method is relatively simple and takes only 15 min to complete.


Assuntos
Articulação do Cotovelo/fisiopatologia , Rigidez Muscular/diagnóstico , Doença de Parkinson/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/uso terapêutico , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rigidez Muscular/tratamento farmacológico , Rigidez Muscular/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Reprodutibilidade dos Testes
14.
Lijec Vjesn ; 113(9-10): 348-52, 1991.
Artigo em Servo-Croata (Latino) | MEDLINE | ID: mdl-1669633

RESUMO

Hepatocerebral degeneration is a hereditary copper metabolic disorder caused by yet unknown pathological process in the 13th chromosome. The disease is more frequent than is usually believed and has systemic characteristics, although the central nervous system and liver are most often affected. The authors describe 35 patients with neurological form of the disease (mean age 29.3 +/- 1.9 years; mean duration of the disease 3.8 +/- 1.7 years). The most frequent symptoms of these patients are dysarthria (88.6%), tremor (85.7%) and rigidity (80%), while elevated liver copper concentration (97.1%) presents the most frequent biochemical disorder of the copper metabolism. Contrary to common opinion about the pathognomy of Kayser-Fleischer ring, its existence is confirmed in only 60% of the patients. On the basis of the author's own results, along with the reference to already described data from literature, the authors give a survey of current knowledge about hepatocerebral degeneration.


Assuntos
Degeneração Hepatolenticular , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/terapia , Humanos
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