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BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1-42 in ALS patients and a control group. METHODS: Our study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann-Whitney U-test. RESULTS: Significant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1-42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS. CONCLUSION: Our study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.
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Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Clusterina , Diagnóstico Tardio , Proteínas tau , BiomarcadoresRESUMO
Neurodegenerative diseases are a broad heterogeneous group affecting the nervous system. They are characterized, from a pathophysiological perspective, by the selective involvement of a subpopulation of nerve cells with a consequent clinical picture of a disease. Clinical diagnoses of neurodegenerative diseases are quite challenging and often not completely accurate because of their marked heterogeneity and frequently overlapping clinical pictures. Efforts are being made to define sufficiently specific and sensitive markers for individual neurodegenerative diseases or groups of diseases in order to increase the accuracy and speed of clinical diagnosis. Thus said, this present research aimed to identify biomarkers in the cerebrospinal fluid (CSF) and serum (α-synuclein [α-syn], tau protein [t-tau], phosphorylated tau protein [p-tau], ß-amyloid [Aß], clusterin, chromogranin A [chromogrA], cystatin C [cyst C], neurofilament heavy chains [NFH], phosphorylated form of neurofilament heavy chains [pNF-H], and ratio of tau protein/amyloid beta [Ind tau/Aß]) that could help in the differential diagnosis and differentiation of the defined groups of α-synucleinopathies and four-repeat (4R-) tauopathies characterized by tau protein isoforms with four microtubule-binding domains. In this study, we analyzed a cohort of 229 patients divided into four groups: (1) Parkinson's disease (PD) + dementia with Lewy bodies (DLB) (n = 82), (2) multiple system atrophy (MSA) (n = 25), (3) progressive supranuclear palsy (PSP) + corticobasal syndrome (CBS) (n = 30), and (4) healthy controls (HC) (n = 92). We also focused on analyzing the biomarkers in relation to each other with the intention of determining whether they are useful in distinguishing among individual proteinopathies. Our results indicate that the proposed set of biomarkers, when evaluated in CSF, is likely to be useful for the differential diagnosis of MSA versus 4RT. However, these biomarkers do not seem to provide any useful diagnostic information when assessed in blood serum.
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Deep brain stimulation (DBS) is a beneficial procedure for treating idiopathic Parkinson's disease (PD), essential tremor, and dystonia. The authors describe their set of imaging modalities used for a frameless and fiducial-less method of DBS. CT and MRI scans are obtained preoperatively, and STN parcellation is done based on diffusion tractography. During the surgery, an intraoperative cone-beam computed tomography scan is obtained and merged with the preoperatively-acquired images to place electrodes using a frameless and fiducial-less system. Accuracy is evaluated prospectively. The described sequence of imaging methods shows excellent accuracy compared to the frame-based techniques.
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Interactions between prion protein (PrP) and tau protein have long been discussed, especially in relation to the pathogenesis of neurodegenerative diseases. The presence of tauopathy in the genetic forms of Creutzfeldt-Jakob disease (CJD) brains is not uncommon. Molecular interactions between PrP and tau protein have been demonstrated in animal models; the role is attributed to the structural properties of misfolded isoform of the host-encoded prion protein (PrPSc) aggregates, especially amyloid, which contributes to the phosphorylation of tau protein, which is reflected in the frequent occurrence of tau pathology in inherited prion amyloidoses. The question is the relationship between PrPSc and hippocampal tau pathology without amyloid deposits (i.e. PART and ARTAG) in sporadic CJD (sCJD). The co-occurrence of these two proteinopathies in sCJD brains is quite rare. These pathological entities have been described in only a few cases of sCJD, all of them were older than 70 years. There have been speculations about the possibility of accelerating the course of pre-existing tauopathy or the possibility of accelerating the ageing process in the CJD brains. Here we present the clinical course and neuropathological findings of a patient with sCJD in whom the above mentioned tauopathies PART and ARTAG, considered to be typical for older age, were found as early as 58 years of age. According to the available information, this case represents an unusually early occurrence of age-related tauopathies not only in relation to sCJD, but also in general.
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Síndrome de Creutzfeldt-Jakob , Príons , Tauopatias , Idoso , Animais , Encéfalo/metabolismo , Síndrome de Creutzfeldt-Jakob/genética , Humanos , Proteínas Priônicas/genética , Príons/genética , Príons/metabolismoRESUMO
Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-ß-d-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-ß-d-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 µM, but this derivative suffered from cytotoxicity at higher concentrations. Both compounds modulated oxidative stress and caspase-3,7 activity, but 10 showed a superior effect comparable to the Ac-DEVD-CHO inhibitor. Interestingly, while both 4 and 10 outperformed the positive controls in blocking mitochondrial permeability transition pore opening, only 4 demonstrated potent restoration of the mitochondrial membrane potential (MMP) in the model. Derivatives 4 and 10 also showed neuroprotection in the Glu model, with 10 exhibiting the strongest oxidative stress reducing effect among the tested compounds, while the neuroprotective activity of 4 was probably due recovery of the MMP.
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Ácido Glutâmico/metabolismo , Isoquinolinas/antagonistas & inibidores , Modelos Biológicos , Fármacos Neuroprotetores/farmacologia , Triazóis/farmacologia , Triterpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Isoquinolinas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Relação Estrutura-Atividade , Triazóis/química , Triterpenos/síntese química , Triterpenos/químicaRESUMO
Cytokinins are adenine-based phytohormones that regulate key processes in plants, such as cell division and differentiation, root and shoot growth, apical dominance, branching, and seed germination. In preliminary studies, they have also shown protective activities against human neurodegenerative diseases. To extend knowledge of the protection (protective activity) they offer, we investigated activities of natural cytokinins against salsolinol (SAL)-induced toxicity (a Parkinson's disease model) and glutamate (Glu)-induced death of neuron-like dopaminergic SH-SY5Y cells. We found that kinetin-3-glucoside, cis-zeatin riboside, and N6-isopentenyladenosine were active in the SAL-induced PD model. In addition, trans-, cis-zeatin, and kinetin along with the iron chelator deferoxamine (DFO) and the necroptosis inhibitor necrostatin 1 (NEC-1) significantly reduced cell death rates in the Glu-induced model. Lactate dehydrogenase assays revealed that the cytokinins provided lower neuroprotective activity than DFO and NEC-1. Moreover, they reduced apoptotic caspase-3/7 activities less strongly than DFO. However, the cytokinins had very similar effects to DFO and NEC-1 on superoxide radical production. Overall, they showed protective activity in the SAL-induced model of parkinsonian neuronal cell death and Glu-induced model of oxidative damage mainly by reduction of oxidative stress.
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Citocininas/uso terapêutico , Modelos Biológicos , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Reguladores de Crescimento de Plantas/farmacologia , Acetilcisteína/farmacologia , Caspase 3/metabolismo , Caspase 7/metabolismo , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocininas/farmacologia , Ácido Glutâmico/toxicidade , Humanos , Isoquinolinas/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Doença de Parkinson/patologia , Superóxidos/metabolismoRESUMO
BACKGROUND: Gait disturbance accompanies many neurodegenerative diseases; it is characteristic for Parkinson's disease (PD). Treatment of advanced PD often includes deep brain stimulation (DBS) of the subthalamic nucleus. Regarding gait, previous studies have reported non-significant or conflicting results, possibly related to methodological limitations. OBJECTIVE: The objective of this prospective study was to assess the effects of DBS on biomechanical parameters of gait in patients with PD. METHODS: Twenty-one patients with advanced PD participated in this prospective study. Gait was examined in all patients using the Zebris FDM-T pressure-sensitive treadmill (Isny, Germany) before DBS implantation and after surgery immediately, further immediately after the start of neurostimulation, and 3 months after neurostimulator activation. We assessed spontaneous gait on a moving treadmill at different speeds. Step length, stance phase of both lower limbs, double-stance phase, and cadence were evaluated. RESULTS: In this study, step length increased, allowing the cadence to decrease. Double-stance phase duration, that is, the most sensitive parameter of gait quality and unsteadiness, was reduced, in gait at a speed of 4.5 km/h and in the narrow-based gaits at 1 km/h (tandem gait), which demonstrates improvement. CONCLUSION: This study suggests positive effects of DBS treatment on gait in PD patients. Improvement was observed in several biomechanical parameters of gait.
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BACKGROUND AND PURPOSE: Ischemic strokes (IS) occur also in young adults and despite an extensive work-up the cause of IS remains very often cryptogenic. Thus, effectiveness of secondary prevention may be unclear. We aimed to analyze a relationship among vascular risk factors (VRF), clinical and laboratory parameters, outcomes and recurrent IS (RIS) in young cryptogenic IS (CIS) patients. SUBJECTS AND METHODS: The study set consisted of young acute IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). All analyzed patients underwent transesophageal echocardiography, 24-h and 3-week ECG-Holter to assess cause of IS according to the ASCOD classification. Recurrent IS (RIS) was recorded during a follow-up (FUP). RESULTS: Out of 294 young enrolled patients, 208 (70.7%, 113 males, mean age 41.6 ± 7.2 years) were identified as cryptogenic. Hyperlipidemia (43.3%), smoking (40.6%) and arterial hypertension (37.0%) were the most frequent VRF. RIS occurred in 7 (3.4%) patients during a mean time of FUP 19 ± 23 months. One-year risk of RIS was 3.4% (95%CI: 1.4-6.8%). Patients with RIS were older (47.4 vs. 41.1 years, p = 0.007) and more often obese (71.4 vs. 19.7%, p = 0.006), and did not differ in any of other analyzed parameters and VRF. Multivariate logistic regression analysis showed obesity (OR: 9.527; 95%CI: 1.777-51.1) and the previous use of antiplatelets (OR: 15.68; 95%CI: 2.430-101.2) as predictors of recurrent IS. CONCLUSION: Despite a higher presence of VRF in young CIS patients, the risk of RIS was very low. Obesity and previous use of antiplatelet therapy were found the only predictors of RIS.
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Isquemia Encefálica/diagnóstico , Ecocardiografia Transesofagiana , Eletrocardiografia Ambulatorial , Acidente Vascular Cerebral/diagnóstico , Adulto , Idade de Início , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Fatores de TempoRESUMO
INTRODUCTION: Despite early management and technical success of mechanical thrombectomy (MT) for acute ischemic stroke (AIS), not all patients reach a good clinical outcome. Different factors may have an impact and we aimed to evaluate blood pressure (BP) levels in the first 24 hours after MT. METHODS: Consecutive AIS patients treated with MT were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale (mRS) with a score 0-2 for good outcome. The presence of symptomatic intracerebral hemorrhage (SICH) was assessed according to the SITS-MOST criteria. RESULTS: Of 703 treated patients, completed BP levels were collected in 690 patients (350 males, mean age 71±13 years) with median of admission NIHSS 17 points. Patients with mRS 0-2 had a lower median of systolic BP (SBP) compared with those with poor outcome (131 vs 140 mm Hg, P<0.0001). The rate of SICH did not differ between the patients with a median of SBP <140 mm Hg and ≥140 mm Hg. (5.1% vs 5.1%, P=0.980). Multivariate regression analysis with adjustment for potential confounders showed a median of distolic BP (P=0.024, OR: 0.977, 95% CI: 0.957 to 0.997) as a predictor of good functional outcome after MT, and a median of maximal SBP (P=0.038; OR: 0.990, 95% CI: 0.981 to 0.999) in the patients with achieved recanalization. CONCLUSION: Lowering of BP within the first 24 hours after MT may have a positive impact on clinical outcome in treated patients.
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Pressão Sanguínea/fisiologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/tendências , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/fisiopatologia , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/fisiopatologia , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction, potentially leading to severe disability. Abnormal cervical spine magnetic resonance imaging (MRI) and motor evoked potentials (MEPs) are independent predictors of disease progression. Abnormal MRI is accompanied by various activation changes in functional brain MRI (fMRI), whereas preoperative and postoperative fMRI adaptations associated with abnormal preoperative MEP remain unknown. METHODS: Twenty patients (9 males, average age 56.6) with evidence of spinal cord compression on MRI and clinical signs of mild CSM were included. Participants were classified according to their preoperative MEP and underwent three brain fMRI examinations: before surgery, 6, and 12 months after surgery while performing repeated extension-flexion of each wrist. RESULTS: Functional MRI activation was compared between two subsets of patients, with normal and clearly abnormal MEP (right wrist: 8 vs. 8; left wrist: 7 vs. 9). At baseline, abnormal MEPs were associated with hyperactivation in the cerebellum. At the first follow-up, further hyperactivations emerged in the contralateral sensorimotor cortices and persisted for 1 year. In normal baseline MEP, activation mostly decreased in the ipsilateral sensorimotor cortex postoperatively. The ipsilateral sensorimotor activation after 1-year follow-up correlated with baseline MEP. CONCLUSIONS: Abnormal corticospinal MEP findings in cervical spondylotic myelopathy were associated with differences in brain activation, which further increased after spinal cord decompression and did not resolve within 12-month follow-up. In summary, surgery may come too late for those patients with abnormal MEP to recover completely despite their mild clinical signs and symptoms.
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Cerebelo/fisiopatologia , Descompressão Cirúrgica/efeitos adversos , Potencial Evocado Motor , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias/fisiopatologia , Compressão da Medula Espinal/cirurgia , Osteofitose Vertebral/cirurgia , Adulto , Idoso , Cerebelo/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Spasticity is a symptom occurring in many neurological conditions including stroke, multiple sclerosis, hypoxic brain damage, traumatic brain injury, tumours and heredodegenerative diseases. It affects large numbers of patients and may cause major disability. So far, spasticity has merely been described as part of the upper motor neurone syndrome or defined in a narrowed neurophysiological sense. This consensus organised by IAB-Interdisciplinary Working Group Movement Disorders wants to provide a brief and practical new definition of spasticity-for the first time-based on its various forms of muscle hyperactivity as described in the current movement disorders terminology. We propose the following new definition system: Spasticity describes involuntary muscle hyperactivity in the presence of central paresis. The involuntary muscle hyperactivity can consist of various forms of muscle hyperactivity: spasticity sensu strictu describes involuntary muscle hyperactivity triggered by rapid passive joint movements, rigidity involuntary muscle hyperactivity triggered by slow passive joint movements, dystonia spontaneous involuntary muscle hyperactivity and spasms complex involuntary movements usually triggered by sensory or acoustic stimuli. Spasticity can be described by a documentation system grouped along clinical picture (axis 1), aetiology (axis 2), localisation (axis 3) and additional central nervous system deficits (axis 4). Our new definition allows distinction of spasticity components accessible to BT therapy and those inaccessible. The documentation sheet presented provides essential information for planning of BT therapy.
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Toxinas Botulínicas/uso terapêutico , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/tratamento farmacológico , Neurotoxinas/uso terapêutico , Humanos , Transtornos dos Movimentos/tratamento farmacológicoRESUMO
AIMS: The relationship between freezing of gait (FOG) and regional brain atrophy has been intensively investigated, but it is still not clearly understood. The study objective was to test whether grey matter (GM) atrophy contributes to FOG in Parkinson's disease (PD) using a surface-based algorithm. METHODS: We investigated 21 patients with PD, 11 with FOG and 10 without FOG. Both groups were assessed using a FOG questionnaire and Hoehn and Yahr staging. High resolution T1-weighted brain images were acquired for each subject using a 1.5T MRI scanner. A surface-based method implemented in FreeSurfer was used to quantify the GM atrophy. A vertex-wise and region of interest (ROI) comparison of spatially normalized subject data using a general linear model and the Wilcoxon rank sum test were to assess significant group differences. RESULTS: Higher global levels of cortical atrophy were detected in freezers, although this was not statistically significant. The vertex-wise analysis revealed significant local reduction in grey matter thickness in the left supplementary motor area, middle/anterior cingulate cortex, temporal pole and right frontal operculum in freezers at P<0.001, uncorrected. The ROI analysis of average thickness confirmed the regional atrophy in bilateral anterior and posterior cingulate cortices. No significant relative regional cortical atrophy was observed in non-freezers. CONCLUSION: FOG was associated with regional cortical atrophy, especially in mesial frontal and cingulate cortices. Our findings provide additional evidence that the development of FOG in patients with PD is associated with local structural cortical changes.
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Lobo Frontal/patologia , Transtornos Neurológicos da Marcha/etiologia , Substância Cinzenta/patologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Lobo Frontal/diagnóstico por imagem , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/patologia , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/etiologiaRESUMO
OBJECTIVE: The aim of this study was to explore the potential of free comprehensive primary preventive examination (CPPE) combined with cardiorespiratory fitness (CRF) test in terms of its attractiveness for general population and moreover to evaluate the induced behavioural changes. The main focus was on physical activity behaviour (PA). METHODS: In 2009-2013, 250 people (100 men, 150 women) aged 18-65 years were examined. CPPE included assessment of health status and lifestyle, CRF test and individualized counselling. Expectations, reasons and motivations for participating were recorded. The sample was evaluated in terms of age, gender, lifestyle, body mass index, body fat percentage, CRF, and health characteristics. Evaluation according to subjective benefits, perceived effects on health and lifestyle was performed after six months using electronic feedback questionnaires (FQ). Comparison was made within groups formed according to the reported increase in PA. RESULTS: People aged 18-39 years accounted for 72.8% of the sample; mean age 34.4±11.0 years; 40.0% were men. Behavioural and health risks were lower in comparison with the general Czech population, but at least 1 of 5 assessed risk factors was present in 88.8% (low fruit and vegetable consumption 74.8%, low physical activity level (PAL) 45.6%, smoking 19.6%, risky alcohol use 18.8%, and stress load 10.4%). The most represented category of CRF was "endurance-trained" (both genders). CPPE was perceived as a source of information concerning health, CRF and lifestyle. 40.0% of men and 30.7% of women were focused on improvement in CRF. The response rate of FQ was 75.6%. Individuals with low PAL and low CRF provided feedback less often (p<0.05). In terms of perceived effect, 84.1% of the respondents implemented some kind of behavioural change; 60.9% reported increase in PA, but only 38.1% reported maintaining improvement in PA after 6 months. A higher proportion of reported lasting changes in PA occurred in subjects who were overweight/obese and in those with low CRF. Participants with low PAL and higher number of lifestyle risks more likely increased their PA only temporarily. Improvement in PA was associated with reported changes in diet (p<0.001). In the group of respondents there was an increase in self-perceived PA (SPA) compared to the baseline (p=0.001). Moreover, individuals who reported increase in PA showed improvement in subjectively perceived health. CONCLUSION: The testing of CRF appears to be a promising motivating factor for going through the intervention, especially for younger people and men. CPPE is effective at the individual level in terms of providing information and initiating behavioural changes in PA. However, this type of intervention is less attractive and less effective for individuals with a higher behavioural risk profile.
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Aptidão Cardiorrespiratória , Indicadores Básicos de Saúde , Prevenção Primária , Adolescente , Adulto , Idoso , Antropometria , Pressão Sanguínea , Composição Corporal , República Tcheca , Feminino , Nível de Saúde , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Sonothrombolysis is a new treatment method for patients with acute ischemic stroke (IS). Various ultrasound frequencies and intensities are being tested these days. The aim of this pilot study was to assess the safety and efficacy of sonothrombolysis using 2 diagnostic probes and bilateral monitoring in patients with acute occlusion of the middle cerebral artery (MCA). PATIENTS AND METHODS: Twelve consecutive IS patients (7 males; age 47 - 78, average 64.1 ± 9.4 years) with acute MCA occlusion and contraindication of thrombolysis were included in the study. 60-min bilateral 2-MHz pulsed-wave Doppler monitoring of the area of occlusion was performed in all patients (Group 1). The control group consisted of 37 IS patients (20 males; age 32 - 78, average 62.2 ± 12.1 years) treated with standard sonothrombolysis and selected from the Thrombotripsy Study database (Group 2). The differences in number of recanalized arteries after a 1 h treatment, independent patients (modified Rankin scale [mRS] value of 0 - 2) after 90 days and symptomatic intracerebral hemorrhages (SICH) were statistically evaluated. RESULTS: Complete recanalization was found in 4 (30.0%) Group 1 and in 12 (32.4%) Group 2 patients. Seven (58.3%) Group 1 and 22 (59.5%) Group 2 patients were independent after 90 days. SICH was found in none of Group 1 patients and in 1 (2.7%) of the Group 2 patients (P>0.05 in all cases). CONCLUSION: In this pilot study, sonothrombolysis using 2 probes and bilateral monitoring is safe but not more effective than standard sonothrombolysis in acute IS patients with MCA occlusion.
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Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/terapia , Terapia por Ultrassom , Ultrassonografia Doppler Transcraniana , Adulto , Idoso , Feminino , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Trombólise Mecânica/efeitos adversos , Trombólise Mecânica/métodos , Pessoa de Meia-Idade , Projetos Piloto , Terapia por Ultrassom/efeitos adversosRESUMO
Spinocerebellar ataxia type 28 (SCA28) is an autosomal dominant neurodegenerative disorder caused by missense AFG3L2 mutations. To examine the occurrence of SCA28 in the Czech Republic, we screened 288 unrelated ataxic patients with hereditary (N = 49) and sporadic or unknown (N = 239) form of ataxia for mutations in exons 15 and 16, the AFG3L2 mutation hotspots. A single significant variant, frameshift mutation c.1958dupT leading to a premature termination codon, was identified in a patient with slowly progressive speech and gait problems starting at the age of 68 years. Neurological examination showed cerebellar ataxia, mild Parkinsonian features with predominant bradykinesia, polyneuropathy of the lower limbs, and cognitive decline. However, other common SCA28 features like pyramidal tract signs (lower limb hyperreflexia, positive Babinski sign), ophthalmoparesis or ptosis were absent. The mutation was also found in a patient's unaffected daughter in whom a targeted examination at 53 years of age revealed mild imbalance signs. RNA analysis showed a decreased ratio of the transcript from the mutated AFG3L2 allele relative to the normal transcript in the peripheral lymphocytes of both patients. The ratio was increased by puromycin treatment, indicating that the mutated transcript can be degraded via nonsense-mediated RNA decay. The causal link between the mutation and the phenotype of the patient is currently unclear but a pathogenic mechanism based on AFG3L2 haploinsufficiency rather than the usual dominant-negative effect of missense AFG3L2 mutations reported in SCA28, cannot be excluded.
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Proteases Dependentes de ATP/genética , Mutação da Fase de Leitura/genética , Predisposição Genética para Doença/genética , Ataxias Espinocerebelares/genética , Degenerações Espinocerebelares/genética , ATPases Associadas a Diversas Atividades Celulares , Idoso , República Tcheca , Feminino , Humanos , Oftalmoplegia/genética , Fenótipo , Ataxias Espinocerebelares/diagnósticoRESUMO
BACKGROUND: Stroke and acute myocardial infarction are the leading causes of death and disability in industrialized countries. Multiple interactions exist between the various forms of cardiovascular and cerebrovascular diseases, and risk factors for development of stroke and major cardiovascular events are similar. There is currently no clear link between acute coronary syndrome and stroke, although it has been repeatedly described. In addition, there are currently no clear recommendations for how to proceed in the case of signs of myocardial damage in patients with acute stroke and how to manage the next follow-up. METHODS-DESIGN: In this prospective observational trial, 500 consecutive ischemic stroke patients admitted at the Comprehensive Stroke Center will be enrolled within 12 h from stroke onset. The set of examinations will consist of: 1) Acute brain computed tomography or magnetic resonance imaging 2) Laboratory tests: A) within 12 h from stroke onset: NT pro B-type of natriuretic peptide, pro-atrial natriuretic peptide, creatinekinase MB, troponin T (cTnT), interleukin 6, procalcitonin, high sensitive C-reactive protein and D-dimers. B) control level of cTnT after 4 h from admission C) non-acute laboratory samples within 60 h from stroke onset: glycated haemoglobine, serum lipids; 3) Electrocardiogram (ECG) on admission and 4 h from stroke onset; 4) Transesophageal or transthoracal echocardiography and 24-h ECG-Holter within 15 days from stroke onset; 5) Neurosonological examination within 60 h from stroke onset; 6) Thirty patients with a positive finding of acute myocardial ischemia (ECG, cTnT) will be examined by coronary angiography (CAG); 7) Epidemiological data will be acquired. STATISTICS: The epidemiological characteristics of the whole sample of patients; correlation between differences between group of cardioembolic ischemic stroke patients and group of patients with ischemic stroke of another etiology; correlation of infarction volume on DWI-MRI with the level of cTnT; correlation of the ECG findings with the level of cTnT and clinical signs; correlation of the CAG findings with level of cTnT and ECG findings will be statistically evaluated at the 5% level of statistical significance. CONCLUSION: The main goal of the project is to improve identification of patients with acute coronary syndrome and with concurrent acute ischemic stroke as these patients require specific treatment and secondary prevention of ischemic events. TRIAL REGISTRATION: Clinicaltrials.gov NCT01541163.
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Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , HumanosRESUMO
BACKGROUND: Literature includes evidence of initial predominance of inflammation and later development of neurodegeneration in the pathogenesis of multiple sclerosis (MS). OBJECTIVE: To search for differences in inflammatory and degenerative cerebrospinal fluid (CSF) markers between relapsing-remitting MS (RRMS) and the clinical isolated syndrome (CIS). METHODS: A total of 148 subjects were evaluated, 65 MS patients (45 RRMS and 20 CIS) and 83 controls. The evaluated parameters included albumin quotient and prealbumin, transferrin, C3 and C4 complement factors, haptoglobin, beta-2-microglobulin, orosomucoid, alpha-1-antitrypsin, apolipoprotein A-I, apolipoprotein B, cystatin C, neuron-specific enolase, tau protein, beta-amyloid, oligoclonal IgG band (OCB), and IgG quotient (QIgG). RESULTS: No differences were found in the inflammatory and degenerative CSF markers between patients with RRMS and CIS. QIgG was higher in RRMS than that in CIS but the number of OCB was higher after CIS. Cystatin C levels were significantly lower in RRMS compared to the other groups. It can be considered an indicator of the demyelination degree. Normal values of beta-amyloid were less frequent in RRMS compared to those in controls.
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Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Degeneração Neural/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Doenças Desmielinizantes/patologia , Feminino , Humanos , Imunoglobulinas/líquido cefalorraquidiano , Mediadores da Inflamação/líquido cefalorraquidiano , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/patologia , Degeneração Neural/patologia , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Valor Preditivo dos Testes , Adulto JovemRESUMO
Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disease with a multifactorial etiology. Protein accumulation is speculated by some to play a prominent role in the pathogenesis of PD. The severity of neurodegeneration should correlate with cerebrospinal fluid (CSF) levels of these neurodegenerative markers (NDMs). The aims of the study were to assess the CSF levels of tau protein, beta-amyloid (1-42), cystatin C, and clusterin in patients suffering from PD and in a control group, to compare the CSF levels between the two groups and to correlate them to PD duration. NDMs in the CSF were assessed in 32 patients suffering from PD and in a control group (CG) of 30 patients. The following statistically significant differences in the CSF were found: higher tau protein (p = 0.045) and clusterin levels (p = 0.004) in PD patients versus CG; higher tau protein levels (p = 0.033), tau protein/beta-amyloid (1-42) ratio (p = 0.011), and clusterin (p = 0.044) in patients suffering from PD for <2 years versus patients suffering PD for more than 2 years. No differences between beta-amyloid (1-42) and cystatin C CSF levels were found in the CG and PD patients groups. Significantly higher tau protein and clusterin CSF levels in the group of PD patients with disease duration of <2 years probably reflect the fact that most neurodegenerative changes in PD patients occur in the initial stage of disease.
Assuntos
Proteínas do Líquido Cefalorraquidiano/metabolismo , Degeneração Neural/líquido cefalorraquidiano , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/diagnóstico , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Degeneração Neural/diagnóstico , Degeneração Neural/etiologiaRESUMO
BACKGROUND: The parkinsonian complex of Guam is an endemic neurodegenerative condition, which has been described only in the islands of the Guam archipelago and at the Kii peninsula of Japan. Up to now, only one "sporadic" case has been described (including the autopsy) in Japan. STUDY OBJECTIVE: To describe the clinical, laboratory and neurophysiological characteristics of the neurodegenerative disorder presenting in 4 patients with the complex syndrome of parkinsonism, amyotrophic lateral sclerosis (ALS), and dementia. PATIENTS AND METHODS: Four consecutive patients of Caucasian and Czech origin, presenting with the complex syndrome of slowly progressive parkinsonism, amyotrophic lateral sclerosis and dementia were examined clinically, including neuropsychological examination, and they were assessed using magnetic resonance imaging, electromyography and evoked potentials. The blood and CSF samples were also examined, and the levels of inflammatory and neurodegenerative markers (beta-amyloid, cystatin C and tau-proteins) were assessed. RESULTS: The clinical phenotype in all four patients corresponded to the one described in the parkinsonian complex of Guam, including the presence of a cognitive deficit at the level of mild to severe dementia. The findings of EMG examination in all cases were those typically seen in ALS, and they met the El Escorial criteria. CSF levels of neurodegenerative markers (tau-protein) were elevated in all four patients. CSF levels of inflammatory markers were normal. CONCLUSION: The unique appearance of the syndrome typical for the endemic Guam complex in patients of Caucasian origin in Europe raises a question of endemicity and heredity of the Guam complex and deserves further research.
Assuntos
Demência/complicações , Doença dos Neurônios Motores/complicações , Doença de Parkinson/complicações , Adulto , Idoso , República Tcheca , Demência/líquido cefalorraquidiano , Progressão da Doença , Eletroencefalografia , Eletromiografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/líquido cefalorraquidiano , Degeneração Neural/complicações , Degeneração Neural/patologia , Doença de Parkinson/líquido cefalorraquidianoRESUMO
BACKGROUND: The aim of this study was to test the hypothesis that there is concomitant peripheral nerve involvement in patients suffering from neurodegenerative disorders by correlating motor and peripheral nerve involvement in Parkinson's disease. METHODS AND RESULTS: A total of 23 patients suffering from Parkinson's disease diagnosed strictly according to the UKPDBB criteria were examined. The group comprised 14 males (mean age: 57 years, mean age at onset: 51 years, mean duration of disease: 7 years, mean duration of dopaminergic treatment: 4 years) and 9 females (mean age: 67 years, mean age at onset: 63 years, mean duration of disease: 4 years, mean duration of dopaminergic treatment: 1 year). CONCLUSION: Polyneuropathy was clinically present and confirmed using EMG examination in 10 patients (43.5 %), 5 males and 5 females. This suggests that the neurodegenerative process involves both the central and the peripheral nervous system in Parkinson's patients.