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1.
J Neurol Neurosurg Psychiatry ; 95(6): 504-514, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38443158

RESUMO

BACKGROUND: Leisure-time physical activity (LTPA) protects against vascular diseases. Whether and to what extent different levels of LTPA, including lower ones, benefit stroke prevention is still unclear. METHODS: We searched prospective cohort studies, indexed on PubMed and Scopus, published in English up to 22 April 2023, that investigated, in a general healthy population, the relationship between different predefined LTPA levels, compared with inactivity, and the risk of any type of stroke. We applied random effect modelling for meta-analyses and meta-regression to control for the impact of age and sex. RESULTS: Out of 3064 screened articles, 15 articles on 16 cohorts of subjects were included in meta-analyses, with a total of 752 050 followed-up subjects. Mean follow-up was 125.7±77.5 months. Included studies identified three (none, below target and ideal) to five (none, insufficient, low, moderate and intense) levels of LTPA. In the five studies identifying three levels of LTPA, compared with no LTPA, below target (risk ratio (RR)=0.82, 95% CI=0.75 to 0.88) and ideal LTPA significantly reduced stroke risk (RR=0.71, 95% CI=0.58 to 0.86).Lower levels of LTPA also mitigated stroke risk in studies reporting on four (n=6; RR=0.73, 95% CI=0.62 to 0.87 favouring moderate LTPA over no LTPA) and five levels (n=2; RR=0.71, 95% CI=0.58 to 0.88 favouring moderate LTPA over no LTPA). The benefits of LTPA were independent of age and sex. CONCLUSIONS: According to our results, all levels of LTPA can be beneficial for stroke prevention, including levels currently regarded as low or insufficient. People should be encouraged to be physically active even at the lowest levels. PROSPERO REGISTRATION NUMBER: CRD42023425302.


Assuntos
Exercício Físico , Atividades de Lazer , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Estudos Prospectivos , Fatores de Risco
2.
Brain ; 146(2): 421-437, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36083979

RESUMO

The advancing validation and exploitation of CSF and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases. Further, recent studies have provided evidence of potential new applications of this biomarker also in non-primary neurological diseases. In the present review we summarize the state of the art, future perspectives, but also limitations, of neurofilament light chain protein as a CSF and blood biomarker in several medical fields, including intensive care medicine, surgery, internal medicine and psychiatry. In particular, neurofilament light chain protein is associated with the degree of neurological impairment and outcome in patients admitted to intensive care units or in the perioperative phase and it seems to be highly interconnected with cardiovascular risk factors. Beyond that, interesting diagnostic and prognostic insights have been provided by the investigation of neurofilament light chain protein in psychiatric disorders as well as in the current coronavirus disease-19 pandemic and in normal ageing. Altogether, current data outline a multifaceted applicability of CSF and blood neurofilament light chain protein ranging from the critical clinical setting to the development of precision medicine models suggesting a strict interplay between the nervous system pathophysiology and the health-illness continuum.


Assuntos
COVID-19 , Doenças do Sistema Nervoso , Humanos , Filamentos Intermediários/metabolismo , Doenças do Sistema Nervoso/diagnóstico , Proteínas de Neurofilamentos , Biomarcadores , Prognóstico
3.
J Thromb Thrombolysis ; 57(3): 445-452, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38127260

RESUMO

We aim to compare the outcomes in patients with atrial fibrillation detected after stroke (AFDAS) and their counterparts with known AF (KAF) presenting with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). This observational, prospective study included consecutive patients with acute LVO ischemic stroke of the anterior circulation with AFDAS, KAF and without AF. The primary study outcome was functional independence at 90 days after stroke. The secondary study outcomes were variation of the NIHSS score at 24 h, rate of successful reperfusion, death at 90 days and rate of immediate complications post-procedure. Overall, our cohort included 518 patients with acute ischemic stroke and LVO treated with MT, with 289 (56.8%) without a diagnosis of AF; 107 (21%) with AFDAS; 122 (22.2%) with KAF. There was no significant difference in terms of functional independence at 90 days after stroke between the three groups. Regarding the secondary study outcome, the rate of symptomatic intracranial haemorrhage (sICH) and/or parenchymal hematoma (PH) were significantly higher in the group of patients without AF (respectively, P = 0.030 and < 0.010). Logistic regression analysis showed that the subtypes of AF were not statistically significantly associated with functional independence at 90 days after stroke and with the likelihood of any ICH. Our results suggest that the subtypes of AF are not associated with clinical and safety outcomes of MT in patients with acute stroke and LVO. Further studies are needed to confirm our findings.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , AVC Isquêmico/complicações , Isquemia Encefálica/diagnóstico , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos
4.
Neurol Sci ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679625

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is an acute neurological condition associated with different etiologies, including antibiotic therapy. To date, most data regarding antibiotic-related PRES are limited to case reports and small case series. Here, we report a novel case description and provide a systematic review of the clinico-radiological characteristics and prognosis of available cases of PRES associated with antibiotic therapy. We performed a systematic literature search in PubMed and Scopus from inception to 10 January 2024, following PRISMA guidelines and a predefined protocol. The database search yielded 12 subjects (including our case). We described the case of a 55-year-old female patient with PRES occurring one day after administration of metronidazole and showing elevated serum neurofilament light chain protein levels and favorable outcome. In our systematic review, antibiotic-associated PRES was more frequent in female patients (83.3%). Metronidazole and fluoroquinolones were the most reported antibiotics (33.3% each). Clinical and radiological features were comparable to those of PRES due to other causes. Regarding the prognosis, about one third of the cases were admitted to the intensive care unit, but almost all subjects (90.0%) had a complete or almost complete clinical and radiological recovery after prompt cessation of the causative drug. Antibiotic-associated PRES appears to share most of the characteristics of classic PRES. Given the overall good prognosis of the disease, it is important to promptly diagnose antibiotic-associated PRES and discontinue the causative drug.

5.
J Neurol Neurosurg Psychiatry ; 94(1): 83-86, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35944974

RESUMO

INTRODUCTION: ß-synuclein (ß-syn) is a presynaptic protein, whose cerebrospinal fluid (CSF) levels are increased in patients with Alzheimer's diseases (AD) showing mild cognitive impairment (MCI) and dementia (dem). Here, we aimed to investigate CSF ß-syn in subjects at different AD stages, including preclinical AD (pre-AD), and to compare its behaviour with another synaptic biomarker, α-synuclein (α-syn), and two biomarkers of neuro-axonal damage, namely neurofilament light chain protein (NfL) and total tau protein (t-tau). METHODS: We measured ß-syn, α-syn, t-tau and NfL in CSF of 75 patients with AD (pre-AD n=17, MCI-AD n=28, dem-AD n=30) and 35 controls (subjective memory complaints, SMC-Ctrl n=13, non-degenerative neurological disorders, Dis-Ctrl n=22). RESULTS: CSF ß-syn, α-syn, t-tau were significantly elevated in pre-AD patients compared with controls (p<0.0001, p=0.02 and p=0.0001, respectively), while NfL only increased in dem-AD (p=0.001). Pre-AD cases showed lower t-tau concentrations than MCI-AD (p=0.04) and dem-AD (p=0.01). CSF ß-syn had the best diagnostic performance for the discrimination of pre-AD subjects from all controls (area under the curve, AUC=0.97) and from SMC-Ctrl subjects (AUC=0.99). DISCUSSION: CSF ß-syn increases in the whole AD continuum since the preclinical stage and represents a promising biomarker of synaptic damage in AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , beta-Sinucleína , Proteínas tau/líquido cefalorraquidiano , Disfunção Cognitiva/psicologia , Biomarcadores/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano
6.
Artigo em Inglês | MEDLINE | ID: mdl-35995553

RESUMO

BACKGROUND: Synaptosomal-associated protein 25 (SNAP-25) in cerebrospinal fluid (CSF) is an emerging synaptic biomarker for the early diagnosis of Alzheimer's disease (AD). However, comprehensive studies investigating the marker in Creutzfeldt-Jakob disease (CJD) and in the differential diagnosis of neurodegenerative diseases are still lacking. METHODS: We developed a novel, sensitive ELISA for the measurement of SNAP-25 in CSF. In total, we analysed 316 patients from 6 diagnostic groups comprising patients with AD (n=96), CJD (n=55), Parkinson's disease spectrum (n=41), frontotemporal lobar degeneration (n=25) and amyotrophic lateral sclerosis (n=24) and non-neurodegenerative control patients (n=75). Using receiver operating characteristic curve analysis, we analysed the differential diagnostic potential and compared the results with core AD biomarkers. RESULTS: SNAP-25 CSF concentrations were elevated in AD and CJD (p<0.0001) but not in the other neurodegenerative diseases. Increased levels were observed already at early AD and CJD stages (p<0.0001). In CJD, SNAP-25 levels correlated negatively with survival time (r=-0.33 (95% CI -0.57 to -0.04, p=0.02). For the discrimination of AD from all other diseases except CJD, we observed a good diagnostic performance for CSF SNAP-25 (area under the curve (AUC) 0.85) which was further improved by applying the ratio with CSF amyloid-ß 1-42 (AUC 0.95). For CJD, we could demonstrate a strong differential diagnostic potential against all other groups including AD (AUC 0.97). CONCLUSION: Using the novel established CSF SNAP-25 ELISA, we here demonstrate the applicability of SNAP-25 as an early synaptic biomarker for both AD and CJD with a possible prognostic value in patients with CJD.

7.
Neurol Sci ; 43(8): 4671-4683, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35482160

RESUMO

INTRODUCTION: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet. METHODS: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation. RESULTS: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years; p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL; p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3-10) days, following aggressive treatment and glucose normalization. CONCLUSIONS: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings.


Assuntos
Coma Hiperglicêmico Hiperosmolar não Cetótico , Acidente Vascular Cerebral , Glucose , Hemianopsia , Humanos , Coma Hiperglicêmico Hiperosmolar não Cetótico/complicações , Coma Hiperglicêmico Hiperosmolar não Cetótico/diagnóstico , Coma Hiperglicêmico Hiperosmolar não Cetótico/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Síndrome
8.
J Stroke Cerebrovasc Dis ; 31(3): 106292, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35026496

RESUMO

INTRODUCTION: Early diagnosis and correct risk stratification in patients with transient ischemic attack (TIA) and minor ischemic stroke (MIS) is crucial for the high rate of subsequent disabling stroke. Although highly improved, diagnosis and prognostication of TIA/MIS patients remain still based on clinical and neuroimaging findings, with some inter-rater variability even among trained neurologists. OBJECTIVES: To provide an up-to-date overview of diagnostic and prognostic blood biomarkers in TIA and MIS patients. MATERIAL AND METHODS: We performed a bibliographic search on PubMed database with last access on July 10th 2021. More than 680 articles were screened and we finally included only primary studies on blood biomarkers. RESULTS: In a narrative fashion, we discussed about blood biomarkers investigated in TIA/MIS patients, including inflammatory, thrombosis, neuronal injury and cardiac analytes, antibodies and microRNAs. Other soluble molecules have been demonstrated to predict the risk of recurrent cerebrovascular events or treatment response in these patients. A rapid point of care assay, combining the determination of different biomarkers, has been developed to improve triage recognition of acute cerebrovascular accidents. CONCLUSIONS: The implementation of blood biomarkers in the clinical management of TIA/MIS could ameliorate urgent identification, risk stratification and individual treatment choice. Large prospective and longitudinal studies, adopting standardized sampling and analytic procedures, are needed to clarify blood biomarkers kinetic and their relationship with TIA and minor stroke etiology.


Assuntos
Ataque Isquêmico Transitório , AVC Isquêmico , Biomarcadores/sangue , Humanos , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/terapia , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/terapia , Prognóstico
9.
Int J Mol Sci ; 23(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35805926

RESUMO

SerpinA1 (α1-antitrypsin) is a soluble glycoprotein, the cerebrospinal fluid (CSF) isoforms of which showed disease-specific changes in neurodegenerative disorders that are still unexplored in Alz-heimer's disease (AD). By means of capillary isoelectric focusing immunoassay, we investigated six serpinA1 isoforms in CSF samples of controls (n = 29), AD-MCI (n = 29), AD-dem (n = 26) and Lewy body disease (LBD, n = 59) patients and correlated the findings with CSF AD core biomarkers (Aß42/40 ratio, p-tau, t-tau). Four CSF serpinA1 isoforms were differently expressed in AD patients compared to controls and LBD patients, especially isoforms 2 and 4. AD-specific changes were found since the MCI stage and significantly correlated with decreased Aß42/40 (p < 0.05) and in-creased p-tau and t-tau levels in CSF (p < 0.001). Analysis of serpinA1 isoform provided good di-agnostic accuracy in discriminating AD patients versus controls (AUC = 0.80) and versus LBD patients (AUC = 0.92), with best results in patients in the dementia stage (AUC = 0.97). SerpinA1 isoform expression is altered in AD patients, suggesting a common, albeit disease-specific, in-volvement of serpinA1 in most neurodegenerative disorders.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Doenças Neurodegenerativas , alfa 1-Antitripsina , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Humanos , Doença por Corpos de Lewy/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Isoformas de Proteínas , alfa 1-Antitripsina/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano
10.
Int J Mol Sci ; 23(4)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35216166

RESUMO

Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt-Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.


Assuntos
Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Encefalinas/líquido cefalorraquidiano , Precursores de Proteínas/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/patologia
11.
J Neurol Neurosurg Psychiatry ; 91(11): 1181-1188, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32928934

RESUMO

OBJECTIVE: To compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes. METHODS: We used a single-molecule immunoassay to measure tau and neurofilament light chain (NfL) protein levels in the plasma and assessed CSF total(t)-tau, NfL and protein 14-3-3 levels in patients with prion disease (n=336), non-prion rapidly progressive dementias (n=106) and non-neurodegenerative controls (n=37). We then evaluated each plasma and CSF marker for diagnosis and their association with survival, taking into account the disease subtype, which is a strong independent prognostic factor in prion disease. RESULTS: Plasma tau and NfL concentrations were higher in patients with prion disease than in non-neurodegenerative controls and non-prion rapidly progressive dementias. Plasma tau showed higher diagnostic value than plasma NfL, but a lower accuracy than the CSF proteins t-tau and 14-3-3. In the whole prion cohort, both plasma (tau and NfL) and CSF (t-tau, 14-3-3 and NfL) markers were significantly associated with survival and showed similar prognostic values. However, the intrasubtype analysis revealed that only CSF t-tau in sporadic Creutzfeldt-Jakob disease (sCJD) MM(V)1, plasma tau and CSF t-tau in sCJD VV2, and plasma NfL in slowly progressive prion diseases were significantly associated with survival after accounting for covariates. CONCLUSIONS: Plasma markers have lower diagnostic accuracy than CSF biomarkers. Plasma tau and NfL and CSF t-tau are significantly associated with survival in prion disease in a subtype-specific manner and can be used to improve clinical trial stratification and clinical care.


Assuntos
Proteínas 14-3-3/sangue , Síndrome de Creutzfeldt-Jakob/sangue , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Encefalopatia Espongiforme Bovina/sangue , Encefalopatia Espongiforme Bovina/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Proteínas tau/sangue , Proteínas 14-3-3/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/classificação , Síndrome de Creutzfeldt-Jakob/diagnóstico , Demência/sangue , Demência/líquido cefalorraquidiano , Demência/diagnóstico , Progressão da Doença , Diagnóstico Precoce , Encefalopatia Espongiforme Bovina/classificação , Encefalopatia Espongiforme Bovina/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Doenças Priônicas/sangue , Doenças Priônicas/líquido cefalorraquidiano , Doenças Priônicas/classificação , Doenças Priônicas/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Proteínas tau/líquido cefalorraquidiano
12.
Ann Neurol ; 84(3): 347-360, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30048013

RESUMO

OBJECTIVE: Comprehensively describe the phenotypic spectrum of sporadic fatal insomnia (sFI) to facilitate diagnosis and management of this rare and peculiar prion disorder. METHODS: A survey among major prion disease reference centers in Europe identified 13 patients diagnosed with sFI in the past 20 years. We undertook a detailed analysis of clinical and histopathological features and the results of diagnostic investigations. RESULTS: Mean age at onset was 43 years, and mean disease duration 30 months. Early clinical findings included psychiatric, sleep, and oculomotor disturbances, followed by cognitive decline and postural instability. In all tested patients, video-polysomnography demonstrated a severe reduction of total sleep time and/or a disorganized sleep. Cerebrospinal fluid (CSF) levels of proteins 14-3-3 and t-tau were unrevealing, the concentration of neurofilament light protein (NfL) was more consistently increased, and the real-time quaking-induced conversion assay (RT-QuIC) revealed a positive prion seeding activity in 60% of cases. Electroencephalography and magnetic resonance imaging showed nonspecific findings, whereas fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated a profound bilateral thalamic hypometabolism in 71% of cases. Molecular analyses revealed PrPSc type 2 and methionine homozygosity at PRNP codon 129 in all cases. INTERPRETATION: sFI is a disease of young or middle-aged adults, which is difficult to reconcile with the hypothesis of a spontaneous etiology related to stochastic, age-related PrP misfolding. The combination of psychiatric and/or sleep-related symptoms with oculomotor abnormalities represents an early peculiar clinical feature of sFI to be valued in the differential diagnosis. Video-polysomnography, FDG-PET, and especially CSF prion RT-QuIC and NfL constitute the most promising supportive diagnostic tests in vivo. Ann Neurol 2018;84:347-360.


Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Fenótipo , Doenças Priônicas/líquido cefalorraquidiano , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Adulto , Idade de Início , Idoso de 80 Anos ou mais , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Diagnóstico Diferencial , Eletroencefalografia/métodos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Priônicas/diagnóstico , Distúrbios do Início e da Manutenção do Sono/líquido cefalorraquidiano
13.
Acta Neuropathol ; 133(4): 559-578, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28205010

RESUMO

The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surrogate neurodegenerative biomarker assays, specifically targets the pathological prion protein (PrPSc). In the studies conducted to date in CJD, cerebrospinal fluid (CSF) RT-QuIC showed good diagnostic sensitivity (82-96%) and virtually full specificity. In the present study, we investigated the diagnostic value of both prion RT-QuIC and surrogate protein markers in a large patient population with suspected CJD and then evaluated the influence on CSF findings of the CJD type, and the associated amyloid-ß (Aß) and tau neuropathology. RT-QuIC showed an overall diagnostic sensitivity of 82.1% and a specificity of 99.4%. However, sensitivity was lower in CJD types linked to abnormal prion protein (PrPSc) type 2 (VV2, MV2K and MM2C) than in typical CJD (MM1). Among surrogate proteins markers (14-3-3, total (t)-tau, and t-tau/phosphorylated (p)-tau ratio) t-tau performed best in terms of both specificity and sensitivity for all sCJD types. Sporadic CJD VV2 and MV2K types demonstrated higher CSF levels of p-tau when compared to other sCJD types and this positively correlated with the amount of tiny tau deposits in brain areas showing spongiform change. CJD patients showed moderately reduced median Aß42 CSF levels, with 38% of cases having significantly decreased protein levels in the absence of Aß brain deposits. Our results: (1) support the use of both RT-QuIC and t-tau assays as first line laboratory investigations for the clinical diagnosis of CJD; (2) demonstrate a secondary tauopathy in CJD subtypes VV2 and MV2K, correlating with increased p-tau levels in the CSF and (3) provide novel insight into the issue of the accuracy of CSF p-tau and Aß42 as markers of brain tauopathy and ß-amyloidosis.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Proteínas 14-3-3/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Encéfalo/metabolismo , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fosforilação , Proteínas Priônicas/líquido cefalorraquidiano , Sensibilidade e Especificidade , Manejo de Espécimes , Punção Espinal , Fatores de Tempo
16.
Neurodegener Dis ; 17(4-5): 227-234, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28719891

RESUMO

BACKGROUND AND OBJECTIVE: In Alzheimer disease (AD) inflammation becomes evident throughout the course of the disease. However, the association between inflammation, cognitive impairment, and cerebrospinal biomarkers (Aß42, t-tau, p-tau181, and Aß42/p-tau181 ratio) is poorly understood. METHODS: A large panel of inflammatory cytokines (interleukin [IL]-1ß, IL-1ra, IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and vascular endothelial growth factor) was analyzed using a multiplex immunoassay in 27 patients with a diagnosis of AD dementia and in 18 control subjects. In a subgroup with available cerebrospinal fluid (CSF) samples, cytokines in serum were correlated with the levels of neurodegenerative CSF biomarkers (Aß42, t-tau, p-tau181, and Aß42/p-tau181 ratio). RESULTS: Compared to control subjects, AD patients showed a significant upregulation of IL-10, IL-1ß, and IL-17 serum levels. Several cytokines appeared intercorrelated, and IL-10 in particular presented a significant inverse correlation with CFS levels of Aß42 and the Aß42/p-tau ratio. CONCLUSION: Our findings indicate that serum levels of IL-10 may represent a possible peripheral expression of amyloid beta deposition in AD patients.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Citocinas/sangue , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatística como Assunto , Fator A de Crescimento do Endotélio Vascular/sangue
17.
J Neurol Sci ; 462: 123059, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38850771

RESUMO

BACKGROUND: VGF and neuroserpin are neurosecretory proteins involved in the pathophysiology of neurodegenerative diseases. We aimed to evaluate their cerebrospinal fluid (CSF) concentrations in patients with Alzheimer's disease (AD) and Lewy body disease (LBD). METHODS: We measured CSF VGF [AQEE] peptide and neuroserpin levels in 108 LBD patients, 76 AD patients and 37 controls, and tested their associations with clinical scores and CSF AD markers. RESULTS: We found decreased CSF levels of VGF [AQEE] in patients with LBD and dementia compared to controls (p = 0.016) and patients with AD-dementia (p = 0.011), but with significant influence of age and sex distribution. Moreover, we observed, on the one hand, a significant associations between lower VGF [AQEE] and neuroserpin levels and poorer cognitive performance (i.e., lower Mini-Mental State Examination scores). On the other hand, higher levels of CSF tau proteins, especially pTau181, were significantly associated with higher concentrations of VGF [AQEE] and neuroserpin. Indeed, LBD patients with AD-like CSF profiles, especially T+ profiles, had higher levels of VGF [AQEE] and neuroserpin compared to controls and LBD/T- cases. DISCUSSION: CSF VGF [AQEE] and neuroserpin may show a complex relationship with cognitive decline when the levels are reduced, and with AD pathology when levels are increased. They may represent novel markers of neurosecretory impairment in neurodegenerative disorders.

18.
J Neurol ; 271(3): 1366-1375, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37982851

RESUMO

BACKGROUND: Although previous studies investigated the main predictors of outcomes after endovascular thrombectomy (EVT) in patients aged 80 years and older, less is known about the impact of the procedural features on outcomes in elderly patients. The aim of this study was to investigate the influence of EVT technical procedures on the main 3-month outcomes in a population of patients aged 80 years and older. METHODS: This observational, prospective, single-centre study included consecutive patients with acute LVO ischaemic stroke of the anterior circulation. The study outcomes were functional independence at 3 months after EVT (defined as a mRS score of 0-2), successful reperfusion (mTICI ≥ 2b), incidence of haeamorrhagic transformation, and 90-day all cause of mortality. RESULTS: Our cohort included 497 patients with acute ischaemic stroke due to LVO treated with EVT. Among them, 105 (21.1%) patients were aged ≥ 80 years. In the elderly group, multivariable regression analysis showed that thromboaspiration technique vs stent-retriever was the single independent predictor of favourable post-procedural TICI score (OR = 7.65, 95%CI = 2.22-26.32, p = 0.001). CONCLUSIONS: Our study suggests that EVT for LVO stroke in the elderly could be safe. The use of thromboaspiration was associated with positive reperfusion outcome in this population. Further studies in larger series are warranted to confirm the present results and to evaluate the safety and efficacy of EVT in the elderly and oldest adults.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Adulto , Humanos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/cirurgia , Isquemia Encefálica/complicações , Isquemia Encefálica/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Estudos Retrospectivos , Trombectomia/efeitos adversos , Trombectomia/métodos , AVC Isquêmico/epidemiologia , AVC Isquêmico/cirurgia , Procedimentos Endovasculares/efeitos adversos , Sistema de Registros
19.
J Am Heart Assoc ; : e034783, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874062

RESUMO

There is limited evidence on the outcomes and safety of mechanical thrombectomy (MT) among patients with acute ischemic stroke (AIS) in the context of cardiac diseases. Our study reviews MT in AIS within the context of cardiac diseases, aiming to identify existing and emerging needs and gaps. PubMed and Scopus were searched until December 31, 2023, using a combination of cardiological diseases and "mechanical thrombectomy" or "endovascular treatment" as keywords. Study design included case reports/series, observational studies, randomized clinical trials, and meta-analyses/systematic reviews. We identified 943 articles, of which 130 were included in the review. Results were categorized according to the cardiac conditions. MT shows significant benefits in patients with atrial fibrillation (n=139) but lacks data for stroke occurring after percutaneous coronary intervention (n=2) or transcatheter aortic valve implantation (n=5). MT is beneficial in AIS attributable to infective endocarditis (n=34), although functional benefit may be limited. Controversy surrounds the functional outcomes and mortality of patients with AIS with heart failure undergoing MT (n=11). Despite technical challenges, MT appears feasible in aortic dissection cases (n=4), and in patients with left ventricular assist device or total artificial heart (n=10). Data on AIS attributable to congenital heart disease (n=4) primarily focus on pediatric cases requiring technical modifications. Treatment outcomes of MT in patients with cardiac tumors (n=8) vary because of clot consistency differences. After cardiac surgery stroke, MT may improve outcomes with early intervention (n=13). Available data outline the feasibility of MT in patients with AIS attributable to large-vessel occlusion in the context of cardiac diseases.

20.
Front Cardiovasc Med ; 11: 1369914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500754

RESUMO

Background: Covert atrial fibrillation (AF) is a predominant aetiology of embolic stroke of undetermined source (ESUS). Evidence suggested that AF is more frequently detected by implantable loop recorder (ILR) than by conventional monitoring. However, the predictive factors associated with occult AF detected using ILRs are not well established yet. In this study we aim to investigate the predictors of AF detection in patients with ESUS undergoing an ILR. Methods: This observational multi-centre study included consecutive ESUS patients who underwent ILR implantation. The infarcts were divided in deep, cortical infarcts or both. The infarction sites were categorized as anterior and middle cerebral artery, posterior cerebral artery with and without brainstem/cerebellum involvement. Multivariable logistic regression analysis was performed to investigate variables associated with AF detection. Results: Overall, 3,000 patients were initially identified. However, in total, 127 patients who consecutively underwent ILR implantation were included in our analysis. AF was detected in 33 (26%) out of 127 patients. The median follow-up was 411 days. There were no significant differences in clinical characteristics and comorbidities between patients with and without AF detected. AF was detected more often after posterior cerebral artery infarct with brainstem/cerebellum involvement (p < 0.001) whereas less often after infarction in the anterior and middle cerebral artery (p = 0.021). Multivariable regression analysis demonstrated that posterior cerebral artery infarct with brainstem/cerebellum involvement was an independent predictor of AF detection. Conclusion: Our study showed that posterior circulation infarcts with brainstem/cerebellum involvement are associated with AF detection in ESUS patients undergoing ILR. Larger prospective studies are needed to validate our findings.

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