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Studies on caregiver burden in patients with frontotemporal lobar degeneration are rare, differ methodologically and show variable results. Single center longitudinal pilot study on caregiver burden and potential risk factors in patients with behavioural variant frontotemporal dementia (bvFTD) and semantic (svPPA) and non-fluent variants (nfvPPA) primary progressive aphasia. Forty-six bvFTD, nine svPPA, and six nfvPPA patients and caring relatives were analysed for up to 2 years using the Mini-Mental State Examination as global measure for cognitive performance, Frontal Assessment Battery (frontal lobe functions), Frontal Behavioural Inventory (personality and behaviour), Neuropsychiatric Inventory (dementia-related neuropsychiatric symptoms), Barthel Index and Lawton IADL Scale (basic and instrumental activities of daily living), the Caregiver Strain Index (CSI), and in most participants also the Zarit Burden Interview (ZBI). CSI baseline sum scores were highest in bvFTD (mean ± SD 5.5 ± 3.4, median 5, IQR 6), intermediate in svPPA (2.9 ± 2.3; 3; 3.5) and low in nfvPPA (1.6 ± 2.1; 1; 2). Similar differences of caregiver burden were found using the ZBI. During follow-up, CSI and ZBI sum scores deteriorated in svPPA, not in bvFTD and nfvPPA, and correlated significantly with personality and behaviour, neuropsychiatric symptoms, caregiver age, and instrumental, but not basic activities of daily living, Mini-Mental State Examination scores or frontal lobe functions. This study reveals differences in caregiver burden in variants of frontotemporal lobar degeneration. Caregivers should be systematically asked for caregiver burden from the time of the diagnosis to provide comprehensive support in time.
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Afasia Primária Progressiva , Demência Frontotemporal , Atividades Cotidianas , Sobrecarga do Cuidador , Humanos , Projetos Piloto , SemânticaRESUMO
BACKGROUND: Pupil examination represents a diagnostic and prognostic test in the management of several neurological diseases. Infrared video pupillometry (IVP) is the gold standard, since it is not routinely available, a noninvasive bedside ultrasound assessment has been proposed as an alternative. The aim of this study was to assess the feasibility and reproducibility of ultrasound pupillometry (UP) in comparison with IVP. MATERIALS AND METHODS: 81 subjects (43 men and 38 women, mean age: 52â±â20 years and 49â±â19 years, respectively) with no history of neurophthalmologic disease were enrolled. UP was performed with a 12-MHz linear probe according to current guidelines for orbital insonation. Light and painful stimuli were applied to test pupillary light reflex (PLR) and ciliospinal reflex (CR). In 30 of these subjects IVP examination was performed additionally to obtain intra-observer and inter-observer agreement. RESULTS: Increasing age was associated with a decreased pupillary diameter (PD) at rest, after PLR and CR (R -0.728, pâ<â0.01, R -0.643, pâ<â0.01, R 0.674, pâ<â0.001 respectively), while no association was noticed with time to constriction/dilation. UP measurements were reproducible (rate of inter- and intra-observer agreement: R 0.979, pâ<â0.01, R 0.946, pâ<â0.01 respectively) and concordant with IVP (PLR R 0.831, pâ<â0.01; CR R 0.879, pâ<â0.01). CONCLUSION: According to our study, ultrasound pupillometry is a feasible and reliable technique for bedside pupillary function assessment, and is a good alternative to infrared video pupillometry. Moreover, it represents the only way for functional pupillary assessment in patients with periorbital hematoma.
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Pupila , Reflexo Pupilar , Ultrassonografia , Adulto , Idoso , Feminino , Humanos , Luz , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
Edoxaban is the most recent available representative of the Non-Vitamin K antagonist oral anticoagulants (NOAC). The approval was based on the largest phase III trials of NOACs for stroke prevention in patients with non-valvular atrial fibrillation (AF, ENGAGE-AF), and for the treatment of venous thromboembolism (VTE, HOKUSAI-VTE). In both trials, edoxaban was associated with similar efficacy and a significant reduction in bleeding events with respect to the pre-defined primary safety endpoints, as compared to warfarin.Additionally, the once daily dosing of edoxaban, the clinically investigated strategy for dose-reduction based on clearly defined criteria and the favorable pharmacokinetic profile might further support the clinical applicability of the substance.In the light of recent data, this expert consensus document aims to summarize the latest clinical trial results while providing a concise overview of current guideline recommendations on the management of patients with non-valvular AF and VTE.
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Fibrilação Atrial , Inibidores do Fator Xa/uso terapêutico , Piridinas/uso terapêutico , Acidente Vascular Cerebral , Tiazóis/uso terapêutico , Tromboembolia Venosa , Administração Oral , Anticoagulantes , Fibrilação Atrial/prevenção & controle , Humanos , Tromboembolia Venosa/prevenção & controleRESUMO
Non-vitamin K antagonist oral anticoagulants (NOACs) have a favorable benefit-risk profile compared with vitamin K antagonists. However, the lack of specific reversal agents has made the management of some patients receiving long-term treatment with NOACs problematic in emergency situations such as major bleeding events or urgent procedures. Idarucizumab, a fully humanized Fab antibody fragment that binds specifically and with high affinity to dabigatran, was recently approved for use in adult patients treated with dabigatran when rapid reversal of its anticoagulant effect is required. Clinical experience with idarucizumab is currently limited. We report 11 real-life clinical cases in which idarucizumab was used after multidisciplinary consultation in a variety of emergency situations including severe postoperative bleeding, emergency high-bleeding-risk surgery (hip/spine surgery and neurosurgery), invasive diagnostic testing (lumbar puncture), intracranial bleeding (pre-pontine subarachnoid hemorrhage and lobar intracerebral hemorrhage) and thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke. This case series illustrates the role of idarucizumab in improving patient safety in rare emergency situations requiring rapid reversal of the anticoagulant effect of dabigatran, while highlighting the importance of information and education about the availability and appropriate use of this recently approved specific reversal agent.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Dabigatrana/efeitos adversos , Interações Medicamentosas , Hemorragia/tratamento farmacológico , Idoso , Antitrombinas/efeitos adversos , Gerenciamento Clínico , Emergências , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Humanos , Hemorragias Intracranianas/tratamento farmacológico , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/tratamento farmacológico , Terapia Trombolítica/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT. METHODS: In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12 months to detect thrombus resolution. RESULTS: Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45 ± 16 years and 78% were female. In patients with CSVT, mean baseline D-dimer (p < 0.001) and sPECAM-1 (p < 0.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994; < 0.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (> 198 ng/ml) on admission were associated with delayed venous thrombus resolution at 3 months (AUC = 0.83). CONCLUSION: sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.
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Produtos de Degradação da Fibrina e do Fibrinogênio , Trombose dos Seios Intracranianos , Trombose Venosa , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose dos Seios Intracranianos/sangue , Trombose dos Seios Intracranianos/diagnóstico por imagem , Adulto , Estudos Prospectivos , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagem , Biomarcadores/sangue , Imageamento por Ressonância Magnética , Molécula 1 de Adesão Intercelular/sangue , Seguimentos , IdosoRESUMO
BACKGROUND: Endovascular therapy (EVT) has been established as a major component in the acute treatment of large vessel occlusion stroke. However, it is unclear whether outcome and other treatment-related factors differ if patients are treated within or outside core working hours. METHODS: We analyzed data from the prospective nationwide Austrian Stroke Unit Registry capturing all consecutive stroke patients treated with EVT between 2016 and 2020. Patients were trichotomized according to the time of groin puncture into treatment within regular working hours (08:00-13:59), afternoon/evening (14:00-21:59) and night-time (22:00-07:59). Additionally, we analyzed 12 EVT treatment windows with equal patient numbers. Main outcome variables included favorable outcome (modified Rankin Scale scores of 0-2) 3 months post-stroke as well as procedural time metrics, recanalization status and complications. RESULTS: We analyzed 2916 patients (median age 74 years, 50.7% female) who underwent EVT. Patients treated within core working hours more frequently had a favorable outcome (42.6% vs 36.1% treated in the afternoon/evening vs 35.8% treated at night-time; p=0.007). Similar results were found when analyzing 12 treatment windows. All these differences remained significant in multivariable analysis adjusting for outcome-relevant co-factors. Onset-to-recanalization time was considerably longer outside core working hours, which was mainly explained by longer door-to-groin time (p<0.001). There was no difference in the number of passes, recanalization status, groin-to-recanalization time and EVT-related complications. CONCLUSIONS: The findings of delayed intrahospital EVT workflows and worse functional outcomes outside core working hours in this nationwide registry are relevant for optimization of stroke care, and might be applicable to other countries with similar settings.
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Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Estudos Prospectivos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/etiologia , Terapia Trombolítica/efeitos adversos , Trombectomia/métodos , Isquemia Encefálica/terapiaRESUMO
BACKGROUND AND PURPOSE: Thrombophilic gene alterations are a major risk factor for cerebral sinus vein thrombosis (CSVT). Up to 30% of all patients with cerebral sinus vein thrombosis (CSVT) are found to have thrombophilic defects such as prothrombin mutation (PTM) or factor V Leiden (FVL). Their repercussions on the plasma levels of dabigatran etexilate are unclear. In this prospective case-control study, we aimed to investigate whether thrombophilia in CSVT has an influence on dabigatran peak-plasma levels. METHODS: We monitored 10 patients over 12 months with acute CSVT, genetic thrombophilia with off-label use of dabigatran etexilate 150 mg twice a day and measured dabigatran peak-plasma levels and radiological outcome. We also monitored patients without genetic thrombophilia with dabigatran etexilate 150 mg twice a day and compared the efficiency and dabigatran peak-plasma levels. RESULTS: Patients with homozygote PTM had significantly lower dabigatran peak concentration compared to patients with FVL or the control group (23 ± 4.2 vs. 152.3 ± 27.5 and 159.6 ± 63.08; p-value ≤ 0.05) There was no significant difference in dabigatran etexilate plasma levels between the heterozygote PTM group compared to patients with FVL or the control group (p = 0.29). There was no correlation between dabigatran peak concentration and delayed thrombus dissolution. CONCLUSIONS: Dabigatran peak concentration was stable in patients with heterozygote FVL and heterozygote PTM, but not in homozygote PTM, compared to controls. Genetic screening for thrombophilia in patients after CSVT may be useful to make patient tailored therapeutic decisions regarding oral anticoagulation and may decrease thrombotic events.
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Introduction: Epidemiological studies show that increased physical activity is linked to a lower risk of breast cancer and mortality. As a result, physical activity can significantly improve patients' quality of life (QOL) both during and after therapy.Many breast cancer patients demonstrate a decrease in cognitive capacity, referred to as the symptom-complex cancer related cognitive impairment (CRCI). Most frequently reported impairments are mild to moderate deficits in processing speed, attention, memory, and executive functions. Cognitive symptoms persist for months or even years, following medical treatment in roughly 35% of afflicted people, impairing everyday functioning, limiting the ability to return to work, and lowering the overall QOL. Recent studies point toward a key role of inflammatory pathways in the CRCI genesis. Attention to physical activity as a potential supportive care option is therefore increasing. However, evidence for the positive effects of exercise on preventing CRCI is still lacking. Patients and Methods: Against this background, the prospective, two-arm, 1:1 randomized, controlled trial investigates the influence of first line chemotherapy accompanied by exercise training on preventing CRCI in 126 patients with breast cancer at the local University Hospital. The study will evaluate biomarkers and secondary assessments suspected to be involved in the pathogenesis of CRCI in addition to objective (primary outcome) and subjective cognitive function. CRCI is believed to be connected to either functional and/or morphological hippocampal damage due to chemotherapy. Thus, cerebral magnetic resonance imaging (MRI) and hippocampal volume measurements are performed. Furthermore, a specific neuropsychological test battery for breast cancer patients has been developed to detect early signs of cognitive impairments in patients and to be integrated into practice. Discussion: This study will explore how a long-term supervised exercise intervention program might prevent CRCI, enables optimization of supportive care and objectifies limits of psychological and physical resilience in breast cancer patients during and after chemotherapy treatment. Trial Registration: ClinicalTrials.gov: Identifier: NCT04789187. Registered on 09 March 2021.
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OBJECTIVE: To investigate the association of blood pressure BP excursions, defined as greater than 185 SBP or greater than 105 DBP, with the probability of intracranial hemorrhage (ICH) and worse functional outcomes in patients with acute ischemic stroke (AIS) treated with tissue plasminogen activator (tPA). METHODS: We performed a post hoc analysis of the CLOTBUST-ER trial. Serial BP measurements were conducted using automated cuff recording according to the recommended BP protocol guidelines for tPA administration. The outcomes were prespecified efficacy and safety endpoints of CLOTBUST-ER. RESULTS: The mean number of serial BP recordings per patient was 37. Of the 674 patients, 227 (34%) had at least one BP excursion (>185/105âmmHg) during the first 24âh following tPA-bolus. The majority of BP excursions (46%) occurred within the first 75âmin from tPA-bolus. Patients with at least one BP excursion in the first 24âh following tPA bolus had significantly lower rates of independent functional outcome at 90 days (31 vs. 40.1%, Pâ=â0.028). The total number of BP excursions was associated with decreased odds of 24-h clinical recovery (ORâ=â0.88, 95% CI:0.80-0.96), 24-h neurological improvement (ORâ=â0.87, 95% CI: 0.81-0.94), 7-day functional improvement (common ORâ=â0.92, 95% CI: 0.87-0.97), 90-day functional improvement (common ORâ=â0.94, 95% CI: 0.88-0.98) and 90-day independent functional outcome (ORâ=â0.90, 95% CI: 0.82-0.98) in analyses adjusted for potential confounders. DBP excursions were independently associated with increased odds of any intracranial hemorrhage (ORâ=â1.26, 95% CI: 1.04-1.53). CONCLUSION: BP excursions above guideline thresholds during the first 24âh following tPA administration for AIS are common and are independently associated with adverse clinical outcomes.
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Pressão Sanguínea , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Terapia Trombolítica , Pressão Sanguínea/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/farmacologia , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Despite the availability of prevention and therapies of stroke, their implementation in clinical practice, even of low-cost ones, remains poor. In 2015, the European Stroke Organisation (ESO) initiated the ESO Enhancing and Accelerating Stroke Treatment (EAST) program, which aims to improve stroke care quality, primarily in Eastern Europe. Here, we describe its methods and milestones. PATIENTS AND METHODS: The ESO EAST program is using an implementation strategy based on a 'detecting-understanding-reducing disparities' conceptual framework: stroke care quality is first measured (after developing a platform for data collection), gaps are identified in the current service delivery, and ultimately feedback is provided to participating hospitals, followed by the application of interventions to reduce disparities. The ESO EAST program is carried out by establishing a stroke quality registry, stroke management infrastructure, and creating education and training opportunities for healthcare professionals. RESULTS: Program management and leadership infrastructure has been established in 19 countries (Country Representatives in 22 countries, National Steering Committee in 19 countries). A software platform for data collection and analysis: Registry of Stroke Care Quality was developed, and launched in 2016, and has been used to collect data from over 90,000 patients from >750 hospitals and 56 countries between September 2016 and May 2019. Training in thrombolysis, nursing and research skills has been initiated. DISCUSSION: ESO EAST is the first pan-Eastern European (and beyond) multifaceted quality improvement intervention putting evidence-informed policies into practice. Continuous monitoring of stroke care quality allows hospital-to-hospital and country-to-country benchmarking and identification of the gaps and needs in health care.
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BACKGROUND: Results of our recently published phase III randomized clinical trial of ultrasound-enhanced thrombolysis (sonothrombolysis) using an operator-independent, high frequency ultrasound device revealed heterogeneity of patient recruitment among centers. METHODS: We performed a post hoc analysis after excluding subjects that were recruited at centers reporting a decline in the balance of randomization between sonothrombolysis and concurrent endovascular trials. RESULTS: From a total of 676 participants randomized in the CLOTBUST-ER trial we identified 52 patients from 7 centers with perceived equipoise shift in favor of endovascular treatment. Post hoc sensitivity analysis in the intention-to-treat population adjusted for age, National Institutes of Health Scale score at baseline, time from stroke onset to tPA bolus and baseline serum glucose showed a significant (p < 0.01) interaction of perceived endovascular equipoise shift on the association between sonothrombolysis and 3 month functional outcome [adjusted common odds ratio (cOR) in centers with perceived endovascular equipoise shift: 0.22, 95% CI 0.06-0.75; p = 0.02; adjusted cOR for centers without endovascular equipoise shift: 1.20, 95% CI 0.89-1.62; p = 0.24)]. After excluding centers with perceived endovascular equipoise shift, patients randomized to sonothrombolysis had higher odds of 3 month functional independence (mRS scores 0-2) compared with patients treated with tPA only (adjusted OR: 1.53; 95% CI 1.01-2.31; p = 0.04). CONCLUSION: Our experience in CLOTBUST-ER indicates that increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies.
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BACKGROUND: Dysphagia after stroke is common, especially in severely affected patients who have had a tracheotomy. In a pilot trial, pharyngeal electrical stimulation (PES) improved swallowing function in this group of patients. We aimed to replicate and extend this single-centre experience. METHODS: We did a prospective, single-blind, randomised controlled trial across nine sites (seven acute care hospitals, two rehabilitation facilities) in Germany, Austria, and Italy. Patients with recent stroke who required tracheotomy were randomly assigned to receive 3 days of either PES or sham treatment (1:1). All patients had the stimulation catheter inserted; sham treatment was applied by connecting the PES base station to a simulator box instead of the catheter. Randomisation was done via a computerised interactive system (stratified by site) in blocks of four patients per site. Patients and investigators applying PES were not masked. The primary endpoint was assessed by a separate investigator at each site who was masked to treatment assignment. The primary outcome was readiness for decannulation 24-72 h after treatment, assessed using fibreoptic endoscopic evaluation of swallowing and based on a standardised protocol, including absence of massive pooling of saliva, presence of one or more spontaneous swallows, and presence of at least minimum laryngeal sensation. We planned a sequential statistical analysis of superiority for the primary endpoint. Interim analyses were to be done after primary outcome data were available for 50 patients (futility), 70 patients, and every additional ten patients thereafter, up to 140 patients. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN18137204. FINDINGS: From May 29, 2015, to July 5, 2017, of 81 patients assessed, 69 patients from nine sites were randomly assigned to receive PES (n=35) or sham (n=34) treatment. Median onset to randomisation time was 28 days (IQR 19-41; PES 28 [20-49]; sham 28 [18-40]). The Independent Data and Safety Monitoring Board recommended that the trial was stopped early for efficacy after 70 patients had been recruited and primary endpoint data for 69 patients were available. This decision was approved by the steering committee. More patients were ready for decannulation in the PES group (17 [49%] of 35 patients) than in the sham group (three [9%] of 34 patients; odds ratio [OR] 7·00 [95% CI 2·41-19·88]; p=0·0008). Adverse events were reported in 24 (69%) patients in the PES group and 24 (71%) patients in the sham group. The number of patients with at least one serious adverse event did not differ between the groups (ten [29%] patients in the PES group vs eight [23%] patients in the sham group; OR 1·30 [0·44-3·83]; p=0·7851). Seven (20%) patients in the PES group and three (9%) patients in the sham group died during the study period (OR 2·58 [0·61-10·97]; p=0·3059). None of the deaths or serious adverse events were judged to be related to PES. INTERPRETATION: In patients with stroke and subsequent tracheotomy, PES increased the proportion of patients who were ready for decannulation in this study population, many of whom received PES within a month of their stroke. Future trials should confirm whether PES is beneficial in tracheotomised patients who receive stimulation similarly early after stroke and explore its effects in other cohorts. FUNDING: Phagenesis Ltd.
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Transtornos de Deglutição/terapia , Terapia por Estimulação Elétrica/métodos , Avaliação de Resultados em Cuidados de Saúde , Faringe , Acidente Vascular Cerebral/terapia , Traqueotomia/efeitos adversos , Idoso , Cateterismo , Transtornos de Deglutição/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Acidente Vascular Cerebral/complicaçõesRESUMO
OBJECTIVES: Focal cerebral ischemia is responsible for alterations of vascular permeability, and the loss of microvascular integrity is a primary source of subsequent hemorrhages. We evaluated the influence of different durations of ischemia and reperfusion on infarction size and microvascular damage after focal cerebral ischemia in the mouse. METHODS: C57BL/6 mice (n=39) were subjected to focal cerebral ischemia (I) and reperfusion (R). Consecutive brain sections were analysed for infarction volumes (Nissl-staining) and for collagen type IV (immunohistochemistry and western blot). RESULTS: Infarction size (percentage of the infarction volume versus ipsilateral hemisphere) increased with total time of ischemia and reperfusion: 19+/-2% (I3R0), 30+/-2% (I3R3), 36+/-4% (I3R12), 41+/-4% (I1R24), 45+/-6% (I2R24) and 58+/-2% (I3R24). The ischemic hemispheres showed a significant progressive reduction of collagen type IV positive vessels (ischemic versus non-ischemic contralateral area): 90+/-3% (I3R0), 88+/-1% (I3R3), 82+/-3% (I3R12), 85+/-3% (I1R24), 79+/-3% (I2R24), 72+/-2% (I3R24). CONCLUSIONS: Both prolonged ischemia and reperfusion lead to an increased infarction volume, as well as progressive microvascular damage.
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Infarto Encefálico/fisiopatologia , Isquemia Encefálica/fisiopatologia , Infarto da Artéria Cerebral Média/fisiopatologia , Microcirculação/fisiopatologia , Artéria Cerebral Média/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Animais , Membrana Basal/metabolismo , Membrana Basal/patologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Infarto Encefálico/patologia , Isquemia Encefálica/diagnóstico , Colágeno Tipo IV/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Infarto da Artéria Cerebral Média/diagnóstico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/patologia , Artéria Cerebral Média/patologia , Traumatismo por Reperfusão/diagnósticoRESUMO
We describe a novel experimental set-up that allows biochemical, immunohistochemical and morphometric recording of multiple parameters from a single rat brain. The whole brain was cut (coronal sectioning) in a volumetric manner, and 100 cryo-sections (10 microm) were collected from the region of infarction. By use of a scalpel to dissect the cryosection, crude brain material was obtained from the cortical and basal ganglia areas of ischemic and non-ischemic hemispheres. Material from four 10 microm thick sections of the same animal was pooled. About 30 microg protein lysate was extracted per four sections with various lysis buffers; this sufficed for one biochemical or enzymatic test called "micro-Western-blots" or "micro-zymographies". Scraping brain material from cryosections allows the detection of up to 25 parameters from adjacent brain sections of one single rat brain. Different analysis are possible, we have chosen, e.g. to compare factors affecting the basal lamina of cerebral microvessels like the content of the metalloproteinases-2/-9, their tissue inhibitors, the plasminogen activators, collagen type IV, parameters to test the blood-brain barrier: hemoglobin and the protein of the perfusion solution BSA and the infarction volume. On the basis of these parameters it was possible to compare the interactions of the complex processes in the ischemic brain in the same animal in adjacent sections. Thus, this method increases the validity of data comparisons and reduces significantly the number of animals needed in various experimental settings.
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Isquemia Encefálica/fisiopatologia , Encéfalo/patologia , Técnicas Histológicas/métodos , Ratos Wistar , Animais , Western Blotting , Encéfalo/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Masculino , Ratos , Tamanho da AmostraRESUMO
INTRODUCTION: The study was undertaken to evaluate the postganglionic sympathetic sudomotor function employing the quantitative sudomotor axon reflex test (QSART) in tauopathies Alzheimer's disease (AD) and behavioral variant of frontotemporal dementia (bvFTD). METHODS: Patients were recruited in a prospective pilot study. A structured history was taken and QSART was recorded. RESULTS: In all, 15 patients with AD (7 female) and 14 patients with bvFTD (9 female) were included. Mean age (±standard deviation) of patients with AD and bvFTD was 74 ± 9 and 71 ± 10 years, respectively. Severe sudomotor dysfunction (Composite Autonomic Severity sudomotor score 3) was present in 3 (20%) patients with AD and 0 (0%) patients with bvFTD (P = .037). The upper extremity was only involved in 1 patient with AD and 1 patient with bvFTD. Sweat results of the 4 recording sites did not differ between both groups. Patients' history correlated with severe autonomic symptoms as assessed with QSART. CONCLUSION: Postganglionic sudomotor involvement in AD and bvFTD is most likely not part of the disease.
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Doença de Alzheimer/fisiopatologia , Neurônios Colinérgicos/fisiologia , Demência Frontotemporal/fisiopatologia , Sistema Nervoso Periférico/fisiologia , Glândulas Sudoríparas/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Feminino , Demência Frontotemporal/diagnóstico , Gânglios Simpáticos/fisiologia , Humanos , Masculino , Projetos Piloto , Estudos ProspectivosRESUMO
We investigated microvascular damage in areas with magnetic resonance imaging (MRI)-defined apparent diffusion coefficient reduction (ADC-R) in a rat model of thromboembolic occlusion of the middle cerebral artery. Rats received either intracarotid recombinant tissue plasminogen activator (rt-PA) or saline. Microvascular basal lamina damage was quantified by immunohistochemical staining of collagen type IV and by videoimaging analysis. ADC-R positive basal ganglia (cortical) areas showed a significant reduction of stained microvascular area by 15+/-6% (8+/-7%) and the microvascular density by 13+/-5% (8+/-6%) of that on the non-ischemic control side (P<0.001). There were no significant microvascular differences between rats given rt-PA or saline, or between those with or without angiographically proven recanalization. This study reports for the first time that microvascular basal lamina damage in experimental thromboembolic stroke is confined to regions with ADC-R in MRI.
Assuntos
Membrana Basal/patologia , Acidente Vascular Cerebral/patologia , Tromboembolia/patologia , Angiografia/métodos , Animais , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Córtex Cerebelar/metabolismo , Córtex Cerebelar/patologia , Colágeno Tipo II/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica/métodos , Infarto da Artéria Cerebral Média/complicações , Imageamento por Ressonância Magnética/métodos , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia , Ativador de Plasminogênio Tecidual/uso terapêuticoAssuntos
Anemia Hemolítica/terapia , Anticorpos Monoclonais/administração & dosagem , Transplante de Rim/efeitos adversos , Troca Plasmática/métodos , Púrpura Trombocitopênica Trombótica/terapia , Adulto , Anemia Hemolítica/etiologia , Anemia Hemolítica/fisiopatologia , Anticorpos Monoclonais Murinos , Terapia Combinada , Progressão da Doença , Evolução Fatal , Feminino , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Púrpura Trombocitopênica Trombótica/etiologia , Púrpura Trombocitopênica Trombótica/fisiopatologia , Medição de Risco , Rituximab , Índice de Gravidade de Doença , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/terapia , Falha de TratamentoRESUMO
BACKGROUND: Patients with autonomic failure may experience postural dizziness, syncope, and falls. Identifying symptomatic dysautonomia in dementia is of importance to ensure appropriate management and reduce risk of falls. OBJECTIVE: The aim of this prospective study is to identify cardiovascular autonomic dysfunction in patients suffering from behavioral variant of frontotemporal dementia (bvFTD), compared to Alzheimer's disease (AD). METHODS: Patients were prospectively recruited from 2009 until 2013. Clinical autonomic function tests were carried out in an Autonomic Unit according to Ewing's cardiovascular battery. Parasympathetic tests included resting heart rate variability, deep breathing, and Valsalva. Sympathetic function tests compromised blood pressure regulation on valsalva, cutaneous cold stimulation, and 70° head up tilt including of plasma noradrenaline. RESULTS: 26 patients (17 female) with bvFTD and 18 patients (10 female) with AD were examined. Mean age of bvFTD was 69 ± 11 years, AD 74 ± 9 years. History taking was often not conclusive and did not correlate with autonomic signs. In 42% bvFTD patients and 44% AD patients, autonomic dysfunction was demonstrated. Manifest orthostatic hypotension (OH) was present in 19% of bvFTD and 33% AD patients. Frequency of autonomic dysfunction and orthostatic hypotension did not differ between bvFTD and AD, but were significantly higher than in healthy controls. Autonomic dysfunction was associated with an increased risk of falling (assessed with Tinetti Score). CONCLUSION: This is the first prospective study to elucidate autonomic dysfunction in bvFTD patients. There is a considerable higher frequency of cardiovascular dysfunction and OH in bvFTD. History taking may be not conclusive thus cannot exclude cardiovascular dysautonomia.
Assuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Doenças Cardiovasculares/etiologia , Demência Frontotemporal/complicações , Transtornos Mentais/etiologia , Manobra de Valsalva/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Pressão Sanguínea/fisiologia , Temperatura Baixa , Frequência Cardíaca/fisiologia , Humanos , Hipotensão Ortostática/etiologia , Pessoa de Meia-Idade , Norepinefrina/sangue , Estudos Retrospectivos , Pele/inervaçãoRESUMO
Reflex syncope is classified based on the efferent autonomic system as vasodepressant type, cardioinhibitory type and mixed type. We employed quantitative sweat testing to assess differences in sudomotor sympathetic activity in relation to the type of reflex syncope. In cardioinhibitory type sweating started in 7/9 patients after and in vasodepressor type in 11/12 patients before syncope. In mixed type sweating in 20 patients started before and in 10 after syncope. The onset of sweating correlated significantly with the onset of syncope symptoms. These results possibly reflect different onsets of emotional sweating.