A 4-year follow-up of patients with medication-overuse headache previously included in a randomized multicentre study

The aim of this study was to evaluate the long-term outcome in 61 patients with medication-overuse headache (MOH) who 4 years previously had been included in a randomized open-label prospective multicentre study. Sixty patients still alive after 4 years were invited to a follow-up investigation. Fifty patients (83%) participated. Sixteen visited a neurologist, 22 were interviewed through telephone, 2 gave response by a letter, and 10 were evaluated through hospital records. The influence of baseline characteristics on outcome 4 years later was evaluated by non-parametric tests. p values below 0.01 were considered significant. At follow-up, the 50 persons had a mean reduction of 6.5 headache days/month (p < 0.001) and 9.5 acute headache medication days/month (p < 0.001) compared to baseline. Headache index/month was reduced from 449 to 321 (p < 0.001). Sixteen persons (32%) were considered as responders due to a ≥50% reduction in headache frequency from baseline, whereas 17 (34%) persons met the criteria for MOH. None of the baseline characteristics consistently influenced all five outcome measures. Total Hospital Anxiety and Depression Scale (HADS) score at baseline was predictors (p < 0.005) for being a responder after 4 years. At 4 years’ follow-up, one-third of the 50 MOH patients had ≥50% reduction in headache frequency from baseline. A low total HADS score at baseline was associated with the most favorable outcome

Partitioning the Proteome: Phase Separation for Targeted Analysis of Membrane Proteins in Human Post-Mortem Brain

Neuroproteomics is a powerful platform for targeted and hypothesis driven research, providing comprehensive insights into cellular and sub-cellular disease states, Gene × Environmental effects, and cellular response to medication effects in human, animal, and cell culture models. Analysis of sub-proteomes is becoming increasingly important in clinical proteomics, enriching for otherwise undetectable proteins that are possible markers for disease. Membrane proteins are one such sub-proteome class that merit in-depth targeted analysis, particularly in psychiatric disorders. As membrane proteins are notoriously difficult to analyse using traditional proteomics methods, we evaluate a paradigm to enrich for and study membrane proteins from human post-mortem brain tissue. This is the first study to extensively characterise the integral trans-membrane spanning proteins present in human brain. Using Triton X-114 phase separation and LC-MS/MS analysis, we enriched for and identified 494 membrane proteins, with 194 trans-membrane helices present, ranging from 1 to 21 helices per protein. Isolated proteins included glutamate receptors, G proteins, voltage gated and calcium channels, synaptic proteins, and myelin proteins, all of which warrant quantitative proteomic investigation in psychiatric and neurological disorders. Overall, our sub-proteome analysis reduced sample complexity and enriched for integral membrane proteins by 2.3 fold, thus allowing for more manageable, reproducible, and targeted proteomics in case vs. control biomarker studies. This study provides a valuable reference for future neuroproteomic investigations of membrane proteins, and validates the use Triton X-114 detergent phase extraction on human post mortem brain

PET and SPECT Imaging in Hyperkinetic Movement Disorders

Movement disorders can be classified in hypokinetic (e.g., Parkinson's disease, PD) and hyperkinetic disorders (e.g., dystonia, chorea, tremor, tics, myoclonus, and restless legs syndrome). In this chapter, we will discuss results from positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging studies in patients with tremor, tics, myoclonus, and restless legs syndrome. Most studies in patients with tremor included patients with essential tremor (ET): a bilateral, largely symmetric, postural or kinetic tremor mainly involving the upper limbs and sometimes the head. Other studies evaluated patients with orthostatic tremor (OT): an unusually high frequent tremor in the legs that mainly occurs when patients are standing still. Increased regional cerebral blood flow (rCBF) and increased glucose metabolism have been found in the cerebellum, sensorimotor cortex, and thalamus in both patients with ET and OT compared to controls. Both PET and SPECT studies have evaluated the dopamine system in patients with ET and OT. Most imaging studies in patients with ET showed no, or only subtle loss of striatal tracer binding to the dopamine transporter indicating that ET is not characterized by nigrostriatal cell loss. The serotonin and/or gamma-aminobutyric acid (GABA) systems may play a role in the pathophysiology of ET. PET and SPECT imaging of the dopamine and serotonin system in patients with OT showed no abnormalities. Tics, the clinical hallmark of Gilles de la Tourette syndrome (TS), are relatively brief and intermittent involuntary movements (motor tic) and sounds (phonic tic). The essential features of tics are that (1) they can be temporarily suppressed; after suppression a rebound usually occurs with a flurry of tics; (2) the patient experiences an urge to tic, and (3) the tic is followed by a short moment of relief. Using 18F-FDG PET, it was shown that TS is a network disorder where multiple brain areas are active or inactive at the same time. The exact composition of this network is yet to be determined. Using rCBF PET and SPECT many brain regions were found to be abnormal, however, tics mostly correlated with hypoperfusion of the caudate nucleus and cingulate cortex. Both dopamine and serotonin are likely to play a role in the pathophysiology of TS. It is hypothesized that TS is characterized by low serotonin levels that modulate increased phasic dopamine release. Myoclonus is defined as a brief muscle jerk and occurs in many neurologic and non-neurologic disorders. Imaging with PET and SPECT in patients with myoclonus mainly showed abnormalities consistent with the underlying disorder. We described PET and SPECT imaging results in patients in which myoclonus was a prominent symptom. Hypoperfusion and/or hypometabolism of the frontoparietal cortex was found in patients with negative epileptic myoclonus, Alzheimer's disease, corticobasal degeneration, Creutzfeldt-Jakob disease, fatal familiar insomnia, and posthypoxic myoclonus. Other findings that were frequently reported were decreased rCBF and/or glucose metabolism in the cerebellum and thalamus and abnormalities in the dopamine system. Restless legs syndrome (RLS) is defined as an urge to move the legs accompanied with an unpleasant sensation in the legs or in another body part that is especially present during the evening and night and that can be accompanied by periodic limb movements in sleep (PLMS). Imaging studies in these patients have mainly focused on the dopamine system. Most PET studies found decreased tracer binding to the dopamine transporter, although this was not found in SPECT studies. Both PET and SPECT studies showed conflicting results regarding dopamine D2/3 receptor binding: both increased and decreased tracer binding was reported. Furthermore, it is likely that the serotonin and opioid systems also play a role in the pathophysiology of RLS.</p

Desempenho ocupacional das famílias cuidadoras de pessoas com transtornos mentais atendidas em dispositivo de atenção psicossocial

With the process of psychiatric institutionalization, treatment of people with mental disorders, characterized by long before psychiatric hospitalizations, chronicity and social exclusion, went on to defend the humanized care, the integration of the individual in the family and society. The family of the person with a mental disorder, for a considerable time was excluded from the assistance provided to his family. He is currently an important partner of care, since most people who were treated in closed institutions, today live daily with their caregivers, at home. However, families often are not prepared to act as caretakers of close family members with mental disorders, and thus experience a context of overloads in everyday life. It is not uncommon the fact they have not with satisfactory support to deal with the complex situation of caring for a relative who needs care at length in daily life. This research aims to describe the areas of occupational performance (work, rest and sleep, leisure and social participation), the caregivers families before and after the mental illness of his family and the repercussions of this fact in daily life and living conditions of family caregivers; Identify among the areas of occupational performance (work, rest and sleep, leisure and social participation), those considered most important for family caregivers, and the strategies used by them for the development of these areas, with a view to changes in their daily lives and their living conditions. This is a qualitative, critical and reflective study. Approved by the Research Ethics Committee (CEP) of the University Hospital Lauro Wanderley the Federal University of Paraíba, in the period from July 2014 to February 2015. The instrument for data collection was semi-structured interviews. Data collection took place in October and November 2014, after receiving the assent of the CEP. The material was subjected to the analysis of data according to Minayo (2008), following three methodological steps: pre-analysis, material exploration, processing of data and interpretation. The research findings revealed that with regard to the areas of occupational performance (work, rest and sleep, leisure and social participation) of family before becoming caregivers, four of them worked before the mental illness of their relatives and family, by the will of spouse, only performed housework. With regard to rest and sleep, the five family caregivers, two reported not enjoy a good rest and sleep before getting sick of your family, a fact surely occasioned negative impact on the dynamics of your everyday life . The other three caregivers had a good rest and sleep. It was identified that the leisure of the caregivers in this study, before the mental illness of the family, was designed and related to diverse aspects. The five family caregivers interviewed reported an active social participation, whether in church, community groups, in the family. With regard to the areas of occupational performance after mental illness the family, all family caregivers have had to stop work activities outside the home to care for relatives with mental disorders. The rest and sleep of them had to suffer. The leisure and social participation of family caregivers were determined by dynamic behavior of their relatives with mental disorders. With regard to the areas of occupational performance considered the most important by family caregivers, they elected two: rest and sleep and social participation. With the completion of this study, we can see the relevance of the intervention of health workers, because through dialogue and more systematic follow-up to these families, you can help minimize the impact of a life in organized care and overloads generated by these care and so contribute to improving the quality of life of families and caregivers also of users with mental disorders.Com o processo de desinstitucionalização psiquiátrica, o tratamento das pessoas com transtornos mentais antes caracterizados por longas internações psiquiátricas, cronificação e exclusão social, passou a defender o cuidado humanizado, a reinserção do indivíduo na família e na sociedade. A família da pessoa com transtorno mental, durante tempo considerável foi excluída da assistência prestada ao seu familiar. Atualmente é uma importante parceira do cuidado, pois muitas pessoas que eram tratadas em instituições fechadas, hoje convivem diariamente com seus cuidadores, no domicílio. Porém, as famílias, muitas vezes, não estão preparadas para atuar como cuidadoras desses familiares com transtornos mentais, e assim vivenciam um contexto de sobrecargas no cotidiano. Não é raro o fato de não contarem com suporte satisfatório para lidar com a complexa situação de cuidar de um familiar, o qual necessita de cuidados durante um tempo considerável no cotidiano. Esta pesquisa tem como objetivo descrever as áreas de desempenho ocupacional (trabalho; descanso e sono; lazer e participação social), das famílias cuidadoras, antes e após o adoecimento mental dos seus familiares e as repercussões desse fato no cotidiano e nas condições de vida dos familiares cuidadores; Identificar dentre as áreas de desempenho ocupacional (trabalho; descanso e sono; lazer e participação social), as que são consideradas mais importantes para os familiares cuidadores, e as estratégias utilizadas por eles para o desenvolvimento dessas áreas, com vistas a mudanças no seu cotidiano e nas suas condições de vida. Trata-se de estudo qualitativo, crítico e reflexivo. Aprovado pelo Comitê de Ética e Pesquisa (CEP) do Hospital Universitário Lauro Wanderley da Universidade Federal da Paraíba, desenvolvido no período de julho de 2014 a fevereiro de 2015. O instrumento para coleta de dados foi a entrevista semiestruturada. A coleta de dados aconteceu nos meses de outubro e novembro de 2014, após recebimento do parecer favorável do CEP. O material foi submetido a análise de dados segundo Minayo (2008), seguindo três passos metodológicos: pré-análise, exploração do material, tratamento dos dados obtidos e interpretação. Os achados da pesquisa revelaram que no tocante às áreas de desempenho ocupacional (trabalho, descanso e sono, lazer e participação social) dos familiares antes de se tornarem cuidadores, quatro delas trabalhavam antes do adoecimento mental de seus familiares e uma familiar, por vontade do esposo, só realizava trabalhos domésticos. No que diz respeito ao descanso e sono, das cinco cuidadoras familiares, duas relataram não desfrutarem de um bom descanso e sono, antes do processo de adoecimento do seu familiar, fato este, com certeza, que ocasionava repercussões negativas na dinâmica de seu dia a dia. As outras três cuidadoras apresentavam bom descanso e sono. Identificou-se que o lazer das cuidadoras desse estudo, antes do adoecimento mental do familiar, era concebido e relacionado a aspectos diversificados. As cinco cuidadoras familiares entrevistadas relataram uma participação social atuante, seja na igreja, nos grupos comunitários e na família. No que diz respeito às áreas de desempenho ocupacional após o adoecimento mental do familiar, todas as cuidadoras familiares tiveram de interromper as atividades de trabalho fora de casa para cuidar de familiares com transtornos mentais. O descanso e sono delas apresentavam-se prejudicados. O lazer e a participação social das cuidadoras familiares eram determinados pela dinâmica de comportamento dos seus familiares com transtornos mentais. No concernente às áreas de desempenho ocupacional consideradas as mais importantes pelas cuidadoras familiares, estas elegeram duas: descanso e sono e participação social. Com a realização desse estudo, percebe-se a relevância da intervenção dos trabalhadores da saúde, pois mediante o diálogo e acompanhamento mais sistemático a essas famílias, pode-se contribuir para minimizar o impacto de uma vida organizada em cuidados e sobrecargas geradas por esses cuidados e assim colaborar para a melhoria da qualidade de vida das famílias cuidadoras e também dos usuários com transtornos mentais

Glia Protects Neurons against Extracellular Human Neuromelanin

Neuromelanin-containing neurons of the substantia nigra are highly vulnerable to degenerate in Parkinson's disease. Inhibition of the respiratory chain or formation of reactive oxygen species (ROS) by intracellular neuromelanin and triggering of inflammatory processes by extracellular neuromelanin emanating from melanized neurons after their demise are thought to be causally implicated in the high vulnerability of melanized neurons.We addressed the direct effect of purified neuromelanin on mitochondrial complex I activity, and its influence on ROS production and survival of primary mesencephalic neurons in the presence or absence of glia.Neuromelanin was isolated from midbrain of postmortem human brains. The content in iron and other elements was measured by inductively coupled mass spectrometry. The effect of neuromelanin on mitochondrial complex I activity was analyzed in post-nuclear extracts. Primary neuronal enriched and neuron-glia mixed cultures from midbrain were treated with different concentrations of neuromelanin. The generation of ROS was determined by fluorochrome detection. MAP2-positive and TH-positive neuronal viability was analyzed.Neuromelanin did not affect complex I activity, but concentration-dependently increased ROS production in neurons and reduced the number of MAP2-positive and TH-positive cultured neurons. Glia protected neurons against the neuromelanin toxicity.Extracellular neuromelanin is detrimental to neurons implicating a mechanism of intracellular ROS production, but not complex I inhibition. ROS formation may be catalyzed by iron, which was sensitively identified in purified neuromelanin (3.3 mg/g). Importantly, we demonstrate that glial cells have the potential to mitigate the neurotoxic effect of neuromelanin