1,721,051 research outputs found
Rapidly Progressive Alzheimer’s Disease: Contributions to Clinical-Pathological Definition and Diagnosis
No full textRapidly progressive Alzheimer's disease (rpAD) has recently been recognized as a clinical disease subtype characterized by rapidly progressive cognitive decline and/or short disease duration, and the possible occurrence of early focal neurological signs. Consistently, rpAD represents a relatively frequent alternative diagnosis among cases referred as possible or probable Creutzfeldt-Jakob disease (CJD) to surveillance centers for prion disease worldwide. Indeed, the early clinical differential diagnosis between the two disorders can be challenging given the partial overlap in clinical features and cerebrospinal fluid (CSF) levels of the protein surrogate markers 14-3-3 and total-tau. Although typical AD and rpAD seem to share the neuropathological core features, recent evidence suggests that a distinctive molecular signature involving the structure of amyloid-β aggregates and the proteomic landscape of amyloid plaques may distinguish rpAD from typical AD. Here we review clinical, neuropathological, and molecular features and diagnostic findings, including CSF biomarker data, reported to date in rpAD. Furthermore, we summarize the main clinical, pathological and laboratory features of 27 autopsy confirmed cases of rpAD referred to our center. The results of this retrospective analysis, while largely confirming previously published genetic, clinical, and neuropathological data, suggest a higher prevalence of moderate to severe cerebral amyloid angiopathy in rpAD compared to typical AD, a finding to explore further and validate in a larger patient group
Cerebrospinal fluid biomarkers of neurodegeneration in narcolepsy type 1
Full text linkTo measure the levels of five neurodegenerative biomarkers in the cerebrospinal fluid (CSF) of patients with narcolepsy type 1 (NT1) with variable disease duration
Neurofilament light chain and glial fibrillary acidic protein as diagnostic and prognostic biomarkers in epileptic seizures and epilepsy: A systematic review
Full text linkEpileptology − with epilepsy as one of the most common neurological diseases − has an urgent need for easily accessible biomarkers to improve diagnosis, prognosis and therapeutic monitoring. Neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) have emerged as promising fluid biomarkers in various neurological disorders. Their potential role in epileptic seizures and epilepsy remains largely unexplored. To assess the current state of research on this topic we comprehensively searched the published literature for studies on GFAP and/or NfL in cerebrospinal fluid and/or blood in adult humans with epileptic seizures, status epilepticus or epilepsy (last data base search on 10th of May 2024). We identified a total of 2285 publications of which 19 fulfilled our search criteria. The studies targeted various outcomes such as prognosis in status epilepticus, differentiation of seizure semiology and etiology, differentiation of epileptic seizures from non-epileptic conditions, prediction of epilepsy in autoimmune epilepsy, after a stroke or after a first unprovoked seizure, the role of the time interval from seizure to sampling, the association with disease duration as well as seizure frequency and the influence of seizure suppressing medication. The results are heterogeneous but indicate promising applications for both NfL and GFAP in diagnosis and prognostication of patients with epileptic seizures and epilepsy. In the present review we summarize the current evidence, future perspectives, but also limitations, of NfL and GFAP as fluid biomarkers in epilepsy and epileptic seizures
Guillain-Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases
No full textSince coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain-Barre syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most findings were reported in the form of case reports or case series, whereas a comprehensive overview is still lacking. We conducted a systematic review and searched for all published cases until July 20th 2020. We included 73 patients reported in 52 publications. A broad age range was affected (mean 55, min 11-max 94 years) with male predominance (68.5%). Most patients showed respiratory and/or systemic symptoms, and developed GBS manifestations after COVID-19. However, asymptomatic cases for COVID-19 were also described. The distributions of clinical variants and electrophysiological subtypes resemble those of classic GBS, with a higher prevalence of the classic sensorimotor form and the acute inflammatory demyelinating polyneuropathy, although rare variants like Miller Fisher syndrome were also reported. Cerebrospinal fluid (CSF) albuminocytological dissociation was present in around 71% cases, and CSF SARS-CoV-2 RNA was absent in all tested cases. More than 70% of patients showed a good prognosis, mostly after treatment with intravenous immunoglobulin. Patients with less favorable outcome were associated with a significantly older age in accordance with previous findings regarding both classic GBS and COVID-19. COVID-19-associated GBS seems to share most features of classic post-infectious GBS and possibly the same immune-mediated pathogenetic mechanisms. Nevertheless, more extensive epidemiological studies are needed to clarify these issues
Diagnostic and Prognostic Blood Biomarkers in Transient Ischemic Attack and Minor Ischemic Stroke: An Up-To-Date Narrative Review
No full textIntroduction: 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.& nbsp
Ongoing challenges in unravelling the association between COVID-19 and Guillain-Barré syndrome
No full textDiagnostic Accuracy of a Combined Analysis of Cerebrospinal Fluid t-PrP, t-tau, p-tau, and Aβ42 in the Differential Diagnosis of Creutzfeldt-Jakob Disease from Alzheimer's Disease with Emphasis on Atypical Disease Variants
No full textAccording to recent studies, the determination of cerebrospinal fluid (CSF) total tau (t-tau)/phosphorylated tau (p-tau) ratio and total prion protein (t-PrP) levels significantly improves the accuracy of the diagnosis of Alzheimer's disease (AD) in atypical cases with clinical or laboratory features mimicking Creutzfeldt-Jakob disease (CJD). However, this has neither been validated nor tested in series including atypical CJD variants. Furthermore, the added diagnostic value of amyloid-β (Aβ)42 remains unclear. To address these issues, we measured t-PrP, 14-3-3, t-tau, p-tau, and Aβ42 CSF levels in 45 typical and 44 atypical/rapidly progressive AD patients, 54 typical and 54 atypical CJD patients, and 33 controls. CJD patients showed significantly lower CSF t-PrP levels than controls and AD patients. Furthermore, atypical CJD was associated with lower t-PrP levels in comparison to typical CJD. T-tau, 14-3-3, or t-PrP alone yielded, respectively, 80.6, 63.0, and 73.0 sensitivity and 75.3, 92.1, and 75 specificity in distinguishing AD from CJD. On receiver operating characteristic (ROC) curve analyses of biomarker combinations, the (t-tau×Aβ42)/(p-tau×t-PrP) ratio achieved the best accuracy, with 98.1 sensitivity and 97.7 specificity overall, and 96.2 sensitivity and 95.5 specificity for the "atypical" disease groups. Our results show that the combined analysis of CSF t-PrP, t-tau, p-tau, and Aβ42 is clinically useful in the differential diagnosis between CJD and AD. Furthermore, the finding of reduced CSF t-PrP levels in CJD patients suggest that, likewise Aβ42 in AD, CSF t-PrP levels reflect the extent of PrPc conversion into abnormal PrP (PrPSc) and the burden of PrPSc deposition in CJD
Clinical Reasoning: Rapidly progressive dementia in a patient with HIV after an exotic journey
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Implementing Blood Biomarkers in Stroke Research and Clinical Practice
Full text linkBlood-based biomarkers reflecting the severity of brain injury showed manifold promising applications in the management of patients with stroke. To date, NfL (neurofilament light chain) and GFAP (glial fibrillary acidic protein) represent the markers with the most support from the literature, but novel biomarker candidates are emerging. In this commentary, we discuss the potential benefits that blood biomarkers would have as additional tools for physicians and stroke specialists in the assessment of stroke risk in the general population, in the acute and postacute phase of stroke management as well as during the longitudinal monitoring of patients during rehabilitation. Moreover, we present an overview of the current applications of blood biomarkers in ongoing clinical trials and debate the still unmet needs of biomarker research in stroke that future studies should target to ease their implementation in the routine care of patients
The CSF neurofilament light signature in rapidly progressive neurodegenerative dementias
Full text linkAbstract Background Neurofilament light chain protein (NfL) is a surrogate biomarker of neurodegeneration that has never been systematically tested, either alone or in combination with other biomarkers, in atypical/rapidly progressive neurodegenerative dementias (NDs). Methods Using validated, commercially available enzyme-linked immunosorbent assay kits, we measured cerebrospinal fluid (CSF) NfL, total tau (t-tau), phosphorylated tau, and β-amyloid 42 in subjects with a neuropathological or clinical diagnosis of prion disease (n = 141), Alzheimer’s disease (AD) (n = 73), dementia with Lewy bodies (DLB) (n = 35), or frontotemporal lobar degeneration (FTLD) (n = 44). Several cases with an atypical/rapidly progressive course were included in each group. We evaluated the diagnostic accuracy of every CSF biomarker and their combinations by ROC curve analyses. Results In each patient group CSF NfL showed higher levels than in control subjects, reaching the highest values in those with Creutzfeldt-Jakob disease (CJD). In the latter, NfL showed a divergent, subtype-specific correlation with t-tau, depending on the degree of subcortical involvement and disease duration. Most significantly, patients with classic sporadic CJD (sCJD) MM1 showed a significantly lower concentration of CSF NfL than those with sCJD MV2, despite the much higher t-tau levels and the more rapid clinical course. High NfL levels were also detected in most atypical CJD cases, showing a disease duration longer than 2 years and/or borderline/negative results in other CSF assays (e.g., 14-3-3, t-tau, and prion real-time quaking-induced conversion). Rapidly progressive/atypical cases showed higher NfL levels than typical patients in FTLD, but not in AD or DLB. NfL showed accuracy similar to that of t-tau in discriminating CJD from other NDs, but it had higher efficacy in differentiating atypical forms, especially in regard to Alzheimer’s disease. Conclusions The present data indicate that CSF NfL and t-tau levels reflect distinct pathophysiological mechanisms of neurodegeneration and support the clinical use of NfL as a fast screening biomarker for the differential diagnosis of atypical/rapidly progressive NDs
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