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1.
BMC Pulm Med ; 22(1): 183, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525938

RESUMO

BACKGROUND: Transforming Growth Factor-ß1 (TGF-ß1) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-ß1 are associated with neutrophilic inflammation, lung fibrosis and loss of pulmonary function. AIM: The aim of this study was to assess the relationship between genetic TGF-ß1 polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-ß1 polymorphisms on inflammatory cytokines in sputum was investigated. METHODS: 56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-ß1 sequence using the SNaPshot® technique. Individual "slopes" in forced expiratory volume in 1 s (FEV1) for all patients were calculated by using documented lung function values of the previous five years. The status of Pseudomonas aeruginosa (Pa) infection was determined. Sputum concentrations of the protease elastase, the serine protease inhibitor elafin and the cytokines IL-1ß, IL-8, IL-6, TNF-α were measured after a standardized sputum induction and processing. RESULTS: The homozygous TT genotype at codon 10 was associated with a lower rate of chronic Pa infection (p < 0.05). The heterozygous GC genotype at codon 25 was associated with lower lung function decline (p < 0.05). Patients with homozygous TT genotype at the promotor SNP showed higher levels of TNF-α (p < 0,05). Higher levels of TGF-ß1 in plasma were associated with a more rapid FEV1 decline over five years (p < 0.05). CONCLUSIONS: Our results suggest that polymorphisms in the TGF-ß1 gene have an effect on lung function decline, Pa infection as well as levels of inflammatory cytokines. Genotyping these polymorphisms could potentially be used to identify CF patients with higher risk of disease progression. TGF-ß1 inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.


Assuntos
Fibrose Cística , Fator de Crescimento Transformador beta1 , Códon , Fibrose Cística/genética , Citocinas/análise , Progressão da Doença , Genótipo , Humanos , Pulmão , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta1/genética
2.
Exp Mech ; 61(1): 191-201, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33776071

RESUMO

BACKGROUND: Hypertension drives myocardial remodeling, leading to changes in structure, composition and mechanical behavior, including residual stress, which are linked to heart disease progression in a gender-specific manner. Emerging therapies are also targeting constituent-specific pathological features. All previous studies, however, have characterized remodeling in the intact tissue, rather than isolated tissue constituents, and did not include sex as a biological variable. OBJECTIVE: In this study we first identified the contribution of collagen fiber network and myocytes to the myocardial residual stress/strain in Dahl-Salt sensitive rats fed with high fat diet. Then, we quantified the effect of hypertension on the remodeling of the left ventricle (LV), as well as the existence of sex-specific remodeling features. METHODS: We performed mechanical tests (opening angle, ring-test) and histological analysis on isolated constituents and intact tissue of the LV. Based on the measurements from the tests, we performed a stress analysis to evaluate the residual stress distribution. Statistical analysis was performed to identify the effects of constituent isolation, elevated blood pressure, and sex of the animal on the output of both experimental measures and modeling results. RESULTS: Hypertension leads to reduced residual stress/strain intact tissue, isolated collagen fibers, and isolated myocytes in male and female rats. Collagen remains the largest contributor to myocardial residual stress in both normotensive and hypertensive animals. We identified sex-differences in both hypertensive and normotensive animals. CONCLUSIONS: We observed both constituent- and sex-specific remodeling features in the LV of an animal model of hypertension.

3.
Eur J Neurol ; 27(12): 2405-2414, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32677282

RESUMO

BACKGROUND AND PURPOSE: Primitive reflexes may reoccur in various neurodegenerative diseases. However, little is known about their structural and functional correlates in the human brain. Notably, the neural mechanisms underlying a positive palmomental reflex (PMR) are poorly understood. As recent studies link Alzheimer's disease (AD)-related primitive reflexes to a dysfunction of the corticostriatal motor circuit (CMC), we conducted the present study to investigate functional and structural correlates of a positive PMR. We hypothesized an involvement of frontostriatal structures and an impairment of the CMC. METHODS: Using whole-brain resting-state functional connectivity (FC), hypothesis and FC result-based probabilistic tractography, and voxel-based morphometry analyses, we compared two groups of AD patients with either positive (n = 12) or negative PMR (n = 12). RESULTS: No significant differences in grey matter volume or structural connectivity (SC) could be observed between the PMR-positive and PMR-negative groups. In contrast, the PMR-positive group showed a decreased seed-to-voxel FC between the bilateral supplementary motor area and parts of the right-hemispherical caudate nucleus and thalamus and a decreased region of interest (ROI)-to-ROI FC between the left putamen and the left superior frontal gyrus. CONCLUSION: Data suggest that dysfunction of the CMC reflected by decreased FC underlies a positive PMR in patients with AD. The lack of significant grey matter or SC differences might reflect that changes in FC appear before changes in SC in the structures of the CMC and brain atrophy.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Reflexo
4.
Eur J Neurol ; 26(2): 222-e17, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30107062

RESUMO

BACKGROUND AND PURPOSE: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL) and motor and non-motor symptoms in advanced Parkinson's disease (PD). However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and QoL in PD is unclear. METHODS: In this prospective, observational study of 39 patients with PD undergoing STN-DBS, we examined the Parkinson's Disease Questionnaire-8 (PDQ-8), 20-item Toronto Alexithymia Scale (TAS-20), Hospital Anxiety and Depression Scale (HADS), Self-Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination and UPDRS complications (UPDRS-II/-III/-IV) and levodopa-equivalent daily dose (LEDD) pre-operatively and at 5-month follow-up. Outcome changes were tested with Wilcoxon signed-rank or paired t-test when parametric tests were applicable and corrected for multiple comparisons. The relationship between outcome changes was explored with bivariate correlations. Additionally, partial correlations between PDQ-8 and TAS-20 were computed controlling for HADS, SRMI and AES change scores. Predictor analyses for PDQ-8 improvement were calculated for all baseline parameters. RESULTS: The baseline prevalence of alexithymia was 17.9%. We observed significant beneficial effects of STN-DBS on PDQ-8, TAS-20, HADS, UPDRS-II, -III and -IV scores and significant LEDD reduction. The correlation between TAS-20 and PDQ-8 improvements remained significant after controlling for all other aforementioned outcomes. Predictor analyses for PDQ-8 improvement were significant for PDQ-8 and TAS-20. CONCLUSIONS: This is the first report of beneficial effects of STN-DBS on alexithymia. Alexithymia was significantly associated with QoL outcome independent of anxiety, depression, mania and apathy. Our study highlights the importance of alexithymia for holistic assessments of DBS outcomes.


Assuntos
Atividades Cotidianas/psicologia , Sintomas Afetivos/terapia , Estimulação Encefálica Profunda/métodos , Doença de Parkinson/psicologia , Qualidade de Vida/psicologia , Núcleo Subtalâmico/fisiopatologia , Sintomas Afetivos/complicações , Sintomas Afetivos/psicologia , Idoso , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
5.
Nervenarzt ; 90(2): 148-159, 2019 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-29974128

RESUMO

The congenital myasthenic syndromes (CMS) represent a heterogeneous group of diseases with a broad spectrum of phenotypes. The common characteristic is an inherited genetic defect of the neuromuscular junction. Although in some patients the specific gene defect remains to be detected, the increasing identification of causative genes in recent years has already provided unique insights into the functionality of structural proteins at the neuromuscular junction. Neonatal and early childhood onset is observed in most CMS subtypes; however, late onset in adolescence or adulthood also occurs and establishing the diagnosis at these stages imposes particular challenges. To enable appropriate therapeutic interventions for an at least in principle treatable condition, determining the genetic cause is warranted. In this overview, the critical clinical and diagnostic features of the different CMS subtypes are presented and illustrated using typical cases. Furthermore, specific diagnostic clues are outlined. Finally, the overlap between CMS and muscular dystrophies is discussed. Illustrating characteristic patient examples, the essential clinical and additional diagnostic findings of various CMS subtypes and special diagnostic indications are presented.


Assuntos
Síndromes Miastênicas Congênitas , Neurotransmissores , Adulto , Diagnóstico Diferencial , Humanos , Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genética , Síndromes Miastênicas Congênitas/terapia , Junção Neuromuscular/genética , Junção Neuromuscular/patologia , Neurotransmissores/uso terapêutico , Fenótipo
6.
J Water Health ; 16(4): 646-656, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30067245

RESUMO

The study's objectives were to assess the extent to which packaged water producers follow product registration procedures and to assess the relationship between product registration and drinking water quality in Accra, Ghana. Following preliminary analysis of a national water quality survey, 118 packaged sachet water samples were collected by sampling all brands sold by 66 vendors. A sample of vendors was selected from two high-income and two low-income areas of Accra, Ghana. Sachet packaging and labelling details were recorded and compared to a regulatory database to assess product registration. All samples were weighed and tested for faecal indicator bacteria and selected physico-chemical parameters. Product registration numbers and brand names could be matched to regulatory records for 77 of 118 sachets (65.2%). All samples tested were compliant with national water quality standards for faecal indicator bacteria and nitrate. Brand registration was not associated with any of the quality indicators considered. The results of this study suggest that while a substantial proportion of sachet water is sold without formal product registration, the microbial quality of the unlicensed water is consistently high in Accra, Ghana. Further examination of regulatory enforcement and monitoring will be needed to ensure sustained high water quality over time.


Assuntos
Água Potável/química , Embalagem de Alimentos , Qualidade da Água , Gana , Humanos
7.
Nervenarzt ; 89(10): 1123-1130, 2018 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-30120487

RESUMO

BACKGROUND: Neuromuscular diseases in childhood, adolescence and adulthood are rare or very rare diseases and for many of them the prevalence and incidence are unknown. Causal therapies are currently used for individual disease entities only. Nevertheless, new genetic methods, a better understanding of the pathophysiology and multidisciplinary treatment concepts help to improve patient life expectancy and quality of life. As a result, more and more patients with an early disease onset reach adulthood and further care in adult medicine is necessary. This imposes new challenges particularly on neurology and the requirements for interdisciplinary cooperation in adult medicine are increased. OBJECTIVE: How can transition be made meaningful? Where do structural and content problems stand out? MATERIAL AND METHOD: Using the example of Duchenne muscular dystrophy, the content and structural requirements for transition are presented and important aspects and possible problems are pointed out. CONCLUSION: The transition process is complex and requires time and personnel resources. If carried out sensibly, it can lead to a better and more efficient care of patients in the long term and thus can also become economically more effective.


Assuntos
Neurologia , Doenças Neuromusculares , Pediatria , Transição para Assistência do Adulto , Atenção à Saúde , Humanos , Distrofia Muscular de Duchenne , Qualidade de Vida , Transição para Assistência do Adulto/normas
8.
Cereb Cortex ; 26(6): 2882-2894, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26980614

RESUMO

Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1-16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis.


Assuntos
Córtex Motor/fisiopatologia , Plasticidade Neuronal/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana/métodos , Idoso , Idoso de 80 Anos ou mais , Braço/fisiopatologia , Feminino , Força da Mão/fisiologia , Humanos , Pacientes Internados , Imageamento por Ressonância Magnética , Masculino , Córtex Motor/diagnóstico por imagem , Transtornos dos Movimentos/diagnóstico por imagem , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Transtornos dos Movimentos/terapia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Modalidades de Fisioterapia , Recuperação de Função Fisiológica/fisiologia , Descanso , Método Simples-Cego , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento
9.
Z Rheumatol ; 76(7): 640-643, 2017 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-28523511

RESUMO

We report the case of a 32-year-old woman with severely elevated serum creatine kinase (CK; 80,000 U/l) and progressive proximal pareses. As muscular biopsy showed inflammatory infiltrates, polymyositis was suspected and immunosuppressive treatment was initiated. However, clinical improvement could not be achieved. Gene sequencing of the DYSF-gene showed a previously unreported homozygous mutation. In summary, elevated serum CK and inflammatory infiltrates in the muscle biopsy are not specific for polymyositis, but may also occur in degenerative diseases (muscular dystrophy), such as dysferlinopathy.


Assuntos
Disferlina/genética , Imunossupressores/uso terapêutico , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Polimiosite/diagnóstico , Adulto , Biópsia , Creatina Quinase/sangue , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Homozigoto , Humanos , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/tratamento farmacológico , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Polimiosite/tratamento farmacológico , Polimiosite/genética , Polimiosite/patologia , Análise de Sequência de DNA , Falha de Tratamento
10.
Neuroimage ; 130: 248-260, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26892856

RESUMO

Joint attention, the shared attentional focus of at least two people on a third significant object, is one of the earliest steps in social development and an essential aspect of reciprocal interaction. However, the neural basis of joint attention (JA) in the course of development is completely unknown. The present study made use of an interactive eye-tracking paradigm in order to examine the developmental trajectories of JA and the influence of a familiar interaction partner during the social encounter. Our results show that across children and adolescents JA elicits a similar network of "social brain" areas as well as attention and motor control associated areas as in adults. While other-initiated JA particularly recruited visual, attention and social processing areas, self-initiated JA specifically activated areas related to social cognition, decision-making, emotions and motivational/reward processes highlighting the rewarding character of self-initiated JA. Activation was further enhanced during self-initiated JA with a familiar interaction partner. With respect to developmental effects, activation of the precuneus declined from childhood to adolescence and additionally shifted from a general involvement in JA towards a more specific involvement for self-initiated JA. Similarly, the temporoparietal junction (TPJ) was broadly involved in JA in children and more specialized for self-initiated JA in adolescents. Taken together, this study provides first-time data on the developmental trajectories of JA and the effect of a familiar interaction partner incorporating the interactive character of JA, its reciprocity and motivational aspects.


Assuntos
Atenção/fisiologia , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Relações Interpessoais , Comportamento Social , Adolescente , Criança , Movimentos Oculares , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Recompensa
11.
Neuroimage ; 139: 439-449, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27374370

RESUMO

Movements result from a complex interplay of multiple brain regions. These regions are assembled into distinct functional networks depending on the specific properties of the action. However, the nature and details of the dynamics of this complex assembly process are unknown. In this study, we sought to identify key markers of the neural processes underlying the preparation and execution of motor actions that always occur irrespective of differences in movement initiation, hence the specific neural processes and functional networks involved. To this end, EEG activity was continuously recorded from 18 right-handed healthy participants while they performed a simple motor task consisting of button presses with the left or right index finger. The movement was performed either in response to a visual cue or at a self-chosen, i.e., non-cued point in time. Despite these substantial differences in movement initiation, dynamic properties of the EEG signals common to both conditions could be identified using time-frequency and phase locking analysis of the EEG data. In both conditions, a significant phase locking effect was observed that started prior to the movement onset in the δ-θ frequency band (2-7Hz), and that was strongest at the electrodes nearest to the contralateral motor region (M1). This phase locking effect did not have a counterpart in the corresponding power spectra (i.e., amplitudes), or in the event-related potentials. Our finding suggests that phase locking in the δ-θ frequency band is a ubiquitous movement-related signal independent of how the actual movement has been initiated. We therefore suggest that phase-locked neural oscillations in the motor cortex are a prerequisite for the preparation and execution of motor actions.


Assuntos
Sincronização Cortical , Ritmo Delta , Córtex Motor/fisiologia , Movimento , Ritmo Teta , Adulto , Eletroencefalografia , Potenciais Evocados , Feminino , Dedos , Humanos , Masculino , Atividade Motora , Desempenho Psicomotor , Adulto Jovem
12.
N Engl J Med ; 368(7): 610-22, 2013 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-23406026

RESUMO

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).


Assuntos
Terapia por Estimulação Elétrica , Doença de Parkinson/terapia , Qualidade de Vida , Atividades Cotidianas , Adulto , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Terapia Combinada , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Discinesias/etiologia , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Neuroestimuladores Implantáveis/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico , Inquéritos e Questionários , Resultado do Tratamento
13.
Acta Psychiatr Scand ; 134(2): 161-71, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27145324

RESUMO

OBJECTIVE: Alterations of the default mode network (DMN) have been described in patients with neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), and the neurotransmitter serotonin (5-HT) is known to modulate DMN activity. This study aimed to explore the role of 5-HT on the DMN and its functional connectivity (FC) in young patients with ADHD. METHODS: Young male patients with ADHD (n = 12) and healthy controls (n = 10) (both aged 12-17 years) were subjected to acute tryptophan depletion (ATD) and subsequently diminished brain 5-HT synthesis. Three hours after challenge intake (ATD or a balanced control condition, BAL), resting state fMRI scans were obtained. RESULTS: In patients, ATD led to attenuated FC of the right superior premotor cortex (BA 6) with the DMN, comparable to the extent found in controls after BAL administration. ATD lowered FC of the left somatosensory cortex (BA 3) with the DMN, independently of the factor group, but with stronger effects in controls. CONCLUSIONS: Data reveal a serotonergic modulation of FC between BA 6 and 3, known to be relevant for motor planning and sensory perception, and the DMN, thereby possibly pointing toward ATD acting beneficially on neural planning of motor activity in patients with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Encéfalo/fisiopatologia , Vias Neurais/fisiopatologia , Triptofano/deficiência , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Mapeamento Encefálico/métodos , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Descanso , Serotonina/metabolismo
14.
Acta Psychiatr Scand ; 133(4): 310-23, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26292852

RESUMO

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is often linked with impulsive and aggressive behaviour, indexed by high comorbidity rates between ADHD and disruptive behaviour disorders (DBD). The present study aimed to investigate underlying neural activity of reactive aggression in children with ADHD and comorbid DBD using functional neuroimaging techniques (fMRI). METHOD: Eighteen boys with ADHD (age 9-14 years, 10 subjects with comorbid DBD) and 18 healthy controls were administered a modified fMRI-based version of the 'Point Subtraction Aggression Game' to elicit reactive aggressive behaviour. Trials consisted of an 'aggression phase' (punishment for a fictitious opponent) and an 'outcome phase' (presentation of the trial outcome). RESULTS: During the aggression phase, higher aggressive responses of control children were accompanied by higher activation of the ventral anterior cingulate cortex and the temporoparietal junction. Patients displayed inverted results. During the outcome phase, comparison between groups and conditions showed differential activation in the dorsal striatum and bilateral insular when subjects gained points. Losing points was accompanied by differential activation of regions belonging to the insula and the middle temporal sulcus. CONCLUSION: Data support the hypothesis that deficient inhibitory control mechanisms are related to increased impulsive aggressive behaviour in young people with ADHD and comorbid DBD.


Assuntos
Agressão/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico por imagem , Criança , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem/métodos
15.
Cereb Cortex ; 25(9): 3046-56, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24836690

RESUMO

Conventional mass-univariate analyses have been previously used to test for group differences in neural signals. However, machine learning algorithms represent a multivariate decoding approach that may help to identify neuroimaging patterns associated with functional impairment in "individual" patients. We investigated whether fMRI allows classification of individual motor impairment after stroke using support vector machines (SVMs). Forty acute stroke patients and 20 control subjects underwent resting-state fMRI. Half of the patients showed significant impairment in hand motor function. Resting-state connectivity was computed by means of whole-brain correlations of seed time-courses in ipsilesional primary motor cortex (M1). Lesion location was identified using diffusion-weighted images. These features were used for linear SVM classification of unseen patients with respect to motor impairment. SVM results were compared with conventional mass-univariate analyses. Resting-state connectivity classified patients with hand motor deficits compared with controls and nonimpaired patients with 82.6-87.6% accuracy. Classification was driven by reduced interhemispheric M1 connectivity and enhanced connectivity between ipsilesional M1 and premotor areas. In contrast, lesion location provided only 50% sensitivity to classify impaired patients. Hence, resting-state fMRI reflects behavioral deficits more accurately than structural MRI. In conclusion, multivariate fMRI analyses offer the potential to serve as markers for endophenotypes of functional impairment.


Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Aprendizado de Máquina , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/patologia , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Avaliação da Deficiência , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Vias Neurais/irrigação sanguínea , Vias Neurais/patologia , Neuroimagem , Descanso , Índice de Gravidade de Doença
16.
Fortschr Neurol Psychiatr ; 84(5): 281-8, 2016 May.
Artigo em Alemão | MEDLINE | ID: mdl-27299787

RESUMO

The identification of an antibody-associated autoimmune encephalitis underlying diverse syndromes, typically comprising epileptic seizures and neuropsychiatric symptoms, and their favorable prognosis, when treated with immunotherapies, is one of the success stories in neurology in recent years. Here we review current widely used therapy regimens in antibody-associated autoimmune encephalitis and the prognosis of the different antibody-associated sub-forms. The main therapeutic instruments encompass tumor therapy (if tumor is detected) and immunotherapies, though recommendations are mainly based on retrospective data analysis. The primary therapeutic goal is complete remission. The degree to which this can be accomplished depends upon the different sub-forms.


Assuntos
Autoanticorpos/sangue , Encefalite/imunologia , Encefalite/terapia , Epilepsia/imunologia , Epilepsia/terapia , Doença de Hashimoto/imunologia , Doença de Hashimoto/terapia , Imunoterapia/métodos , Transtornos Neurocognitivos/imunologia , Transtornos Neurocognitivos/terapia , Glutamato Descarboxilase/imunologia , Humanos , Imunização Passiva , Imunossupressores/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas do Tecido Nervoso/imunologia , Síndromes Paraneoplásicas/imunologia , Síndromes Paraneoplásicas/terapia , Prognóstico , Proteínas/imunologia , Receptores de N-Metil-D-Aspartato/imunologia
17.
Fortschr Neurol Psychiatr ; 84(12): 756-769, 2016 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-27951607

RESUMO

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic progressive or relapsing autoimmune neuropathy with heterogeneous clinical presentation. Symptoms typically include symmetrical, proximal and/or distal paresis and sensory loss. Atypical CIDP variants are increasingly recognized, including subtypes with rapid onset as well as variants with pure sensory, focal or marked asymmetrical deficits. Diagnosis is established by compatible symptoms, characteristic electrophysiological features and cerebrospinal fluid analysis. In unequivocal cases, inflammatory infiltrates in sural nerve biopsy support the diagnosis. Recent studies suggest that diagnostic imaging techniques such as MRI and nerve ultrasound may become useful tools for establishing the diagnosis. First-line therapies include immunoglobulines, steroids, and plasmapheresis. Immunosuppressant agents and monoclonal antibodies are used in therapy-refractory cases or as cortison-saving agents.


Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Biópsia , Diagnóstico Diferencial , Humanos , Imunoglobulinas/uso terapêutico , Imunossupressores/uso terapêutico , Exame Neurológico , Nervos Periféricos/imunologia , Nervos Periféricos/patologia , Troca Plasmática , Plasmaferese , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Linfócitos T/imunologia
18.
Fortschr Neurol Psychiatr ; 84(4): 222-5, 2016 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-27100847

RESUMO

A 64-year-old diabetic female patient presented with involuntary unilateral hyperkinetic movements of the left limbs. Cranial MRI showed a contralateral high signal intensity putaminal lesion on T1-weighted images without any signal changes in the T2-weighted images. This finding is characteristic for hemichorea-hemiballism associated with insufficiently treated diabetes mellitus. Additionally, proton MR spectroscopy was performed and revealed a decreased N-acetylaspartate/creatine and N-acetylaspartate/choline ratio, indicating neuronal damage of the contralateral putamen.


Assuntos
Coreia/diagnóstico por imagem , Coreia/fisiopatologia , Complicações do Diabetes/diagnóstico por imagem , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Dominância Cerebral/fisiologia , Hiperglicinemia não Cetótica/diagnóstico por imagem , Hiperglicinemia não Cetótica/fisiopatologia , Putamen/diagnóstico por imagem , Putamen/fisiopatologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Colina/metabolismo , Creatina/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Pessoa de Meia-Idade
19.
Fortschr Neurol Psychiatr ; 84(10): 633-639, 2016 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-27788554

RESUMO

The Cologne Apraxia Screening (KAS) was developed to diagnose apraxia following left-hemisphere (LH) stroke. The present study aims at developing a diagnostic tool for patients with right-hemisphere (RH) stroke (KAS-R) by modifying the test material of the KAS and reducing the test items based on psychometric analyses.A total of 100 patients with RH stroke and 77 healthy control participants were tested. Psychometric analyses led to the exclusion of 8 KAS items. The final KAS-R, consisting of 12 items, shows good internal consistency (α = 0.795) as well as high sensitivity (79.4 %) and specificity (84.4 %). Applying a cut-off value of ≤ 46 (out of 48) points, 39 RH stroke patients were diagnosed with apraxia. Significant correlations were found between the KAS-R and an imitation test as well as expert ratings, indicating high construct validity. The results suggest that the KAS-R is a reliable and valid diagnostic tool for apraxic deficits after RH stroke.


Assuntos
Apraxias/diagnóstico , Apraxias/etiologia , Testes Neuropsicológicos , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Afasia/diagnóstico , Afasia/psicologia , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Acidente Vascular Cerebral/psicologia
20.
Fortschr Neurol Psychiatr ; 84(7): 411-8, 2016 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-27471999

RESUMO

Intracranial infectious aneurysms are rare but hazardous complications of an infective endocarditis. To date, there are no evidence-based recommendations for the treatment of patients with this condition. Therefore, it remains an interdisciplinary challenge to decide which treatment steps are required and in which order they should be carried out. To illustrate the interdisciplinary dilemma in the treatment of these patients, we here present a case of a 23-year-old, drug-addicted woman with infectious endocarditis. While antibiotic treatment of the streptococcus-mitis-induced endocarditis stabilized the overall status of the patient, rupture of a basilar artery aneurysm caused her sudden death. We discuss the decision-making processes of the treatment, potential difficulties and dilemmas when dealing with patients suffering from infectious endocarditis and infectious intracranial aneurysm. Based upon case reports, studies and reviews, we present the options and risks of conservative, neurosurgical, endovascular, and cardiosurgical treatment of intracranial infectious aneurysms, and propose a patient-centered, interdisciplinary treatment concept.


Assuntos
Aneurisma Infectado/complicações , Aneurisma Infectado/terapia , Endocardite Bacteriana/complicações , Endocardite Bacteriana/terapia , Comunicação Interdisciplinar , Colaboração Intersetorial , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapia , Assistência Centrada no Paciente , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/terapia , Streptococcus mitis , Adulto , Algoritmos , Aneurisma Roto/complicações , Antibacterianos/uso terapêutico , Encéfalo/patologia , Terapia Combinada , Imagem de Difusão por Ressonância Magnética , Evolução Fatal , Feminino , Humanos , Exame Neurológico
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