64 research outputs found
Editorial: Consequences of the COVID-19 Pandemic on Care for Neurological Conditions
The coronavirus disease 2019 (COVID-19) pandemic has caused a wide range of unprecedentedconsequences, including social, economic, and health disruptions. From the point of view ofhealthcare assistance, COVID-19 has deeply impacted usual practice at all levels since the beginningof 2020. In this setting, neurological assistance has adapted to the circumstances of the pandemic. Infact, because COVID-19 involves neurological symptoms, affected patients require the attention ofneurologists, and the high demand for clinical care entailed the recruitment ofmany neurologists tofrontline assistance (1). In addition, the pandemic has impacted the management of patients withneurological disorders, with changes in the management of relapses, usual follow-up, diagnosticprocedures, implementation or generalization of telemedicine, etc. Lockdown and social isolationwere also very harmful in patients with neurological disorders (2). Furthermore, the treatment ofneurological emergencies, such as stroke, was also compromised because of resource re-allocationduring the emergency, and the fear of patients to attend the hospital.The neurological community needed to share experiences about how to face this globalchallenge. Accordingly, this Research Topic was launched in April 2020 to address these issues.Over 117 manuscripts were submitted, and 76 papers have been published, including originals,reviews, and case reports. Studies have covered the main areas of neurological care, includinggeneral neurological care, stroke, epilepsy, multiple sclerosis, movement disorders, cognitiveneurology, neuromuscular disorders, headache, and neuropediatricsFil: Matias Guiu, Jordi A.. Universidad Complutense de Madrid; EspañaFil: Sung, Sheng Feng. No especifĂca;Fil: Hsieh, Cheng Yang. No especifĂca;Fil: Nezu, Tomohisa. No especifĂca;Fil: Porta Etessam, JesĂșs. Universidad Complutense de Madrid; EspañaFil: Allegri, Ricardo Francisco. FundaciĂłn para la Lucha contra las Enfermedades NeurolĂłgicas de la Infancia; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
Spectrum of Headaches Associated With SARSâCoVâ2 Infection: Study of Healthcare Professionals
Background: Series of patients with SARSâCoVâ2 infection report headache in 6%â15% of cases, although some data suggest that the actual frequency is higher, and that headache is not associated with fever. No study published to date has analyzed the characteristics of headache in these patients.
Objective: To analyze the characteristics of COVIDâ19 related headaches.
Methods: We conducted a survey of Spaniard healthcare professionals who have been infected by SARSâCoVâ2 and presented headache during the course of the disease. The survey addressed respondentsâ medical history and headache characteristics, and we analyzed the association between both.
Results: We analyzed the responses of a sample of 112 healthcare professionals. History of migraine was reported by 20/112 (17.9%) of respondents, history of tensionâtype headache by 8/112 (7.1%), and history of cluster headache was reported by a single respondent; 82/112(73.2%) of respondents had no history of headache. Headache presented independently of fever, around the third day after symptom onset. The previous history of migraine was associated with a higher frequency of pulsating headache (20% in patients with previous migraine vs 4.3% in those with no history of migraine, P = .013).
Conclusion: Headache is often holocranial, hemicranial, or occipital, pressing, and worsens with physical activity or head movements. Because the characteristics of the headache and the associated symptoms are heterogeneous in our survey, we suggest that several patterns with specific pathophysiological mechanisms may underlie the headache associated with COVIDâ19
Application of Machine Learning to Electroencephalography for the Diagnosis of Primary Progressive Aphasia: A Pilot Study
Primary progressive aphasia (PPA) is a neurodegenerative syndrome in which diagnosis is usually challenging. Biomarkers are needed for diagnosis and monitoring. In this study, we aimed to evaluate Electroencephalography (EEG) as a biomarker for the diagnosis of PPA. Methods. We conducted a cross-sectional study with 40 PPA patients categorized as non-fluent, semantic, and logopenic variants, and 20 controls. Resting-state EEG with 32 channels was acquired and preprocessed using several procedures (quantitative EEG, wavelet transformation, autoencoders, and graph theory analysis). Seven machine learning algorithms were evaluated (Decision Tree, Elastic Net, Support Vector Machines, Random Forest, K-Nearest Neighbors, Gaussian Naive Bayes, and Multinomial Naive Bayes). Results. Diagnostic capacity to distinguish between PPA and controls was high (accuracy 75%, F1-score 83% for kNN algorithm). The most important features in the classification were derived from network analysis based on graph theory. Conversely, discrimination between PPA variants was lower (Accuracy 58% and F1-score 60% for kNN). Conclusions. The application of ML to resting-state EEG may have a role in the diagnosis of PPA, especially in the differentiation from controls. Future studies with high-density EEG should explore the capacity to distinguish between PPA variants
Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction
Nimodipine is a 1,4-dihydropyridine derivative that shows a preferential
cerebrovascular activity in experimental animals. Clinical data suggest that
nimodipine has a beneficial effect on the neurologic outcome of patients
suffering an acute ischemic stroke. Our double-blind placebo-controlled
multicenter trial was designed to assess the effects of oral nimodipine on the
mortality rate and neurologic outcome of patients with an acute ischemic stroke.
One hundred sixty-four patients were randomly allocated to receive either
nimodipine tablets (30 mg q.i.d.) or identical placebo tablets for 28 days.
Treatment was always started less than or equal to 48 hours after the acute
event. The Mathew Scale, slightly modified by Gelmers et al, was used for
neurologic assessment. Mortality rate and neurologic outcome after 28 days were
used as evaluation criteria. We considered 123 patients to be valid for the
analysis of efficacy. Mortality rates did not differ significantly between
groups. Neurologic outcome after 28 days of therapy did not differ between
groups. However, when only those patients most likely to benefit from any
intervention (Mathew Scale sum score of less than or equal to 65 at baseline)
were analyzed separately in post hoc-defined subgroups, the nimodipine-treated
subgroups showed a significantly better neurologic outcome. This result suggests
that some patients with acute ischemic stroke will benefit from treatment with
nimodipine tablets
Lipid Metabolic Alterations in the ALSâFTD Spectrum of Disorders
There is an increasing interest in the study of the relation between alterations in systemic lipid metabolism and neurodegenerative disorders, in particular in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). In ALS these alterations are well described and evident not only with the progression of the disease but also years before diagnosis. Still, there are some discrepancies in findings relating to the causal nature of lipid metabolic alterations, partly due to the great clinical heterogeneity in ALS. ALS presentation is within a disorder spectrum with Frontotemporal Dementia (FTD), and many patients present mixed forms of ALS and FTD, thus increasing the variability. Lipid metabolic and other systemic metabolic alterations have not been well studied in FTD, or in ALSâFTD mixed forms, as has been in pure ALS. With the recent development in lipidomics and the integration with other -omics platforms, there is now emerging data that not only facilitates the identification of biomarkers but also enables understanding of the underlying pathological mechanisms. Here, we reviewed the recent literature to compile lipid metabolic alterations in ALS, FTD, and intermediate mixed forms, with a view to appraising key commonalities or differences within the spectrum
Quantification of Unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples
Hypomethylation of DNA is a hallmark of cancer and its analysis as tumor biomarker has been proposed, but its determination in clinical settings is hampered by lack of standardized methodologies. Here, we present QUAlu (Quantification of Unmethylated Alu), a new technique to estimate the Percentage of UnMethylated Alu (PUMA) as a surrogate for global hypomethylation.
QUAlu consists in the measurement by qPCR of Alu repeats after digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation. QUAlu performance has been evaluated for reproducibility, trueness and specificity, and validated by deep sequencing. As a proof of use, QUAlu has been applied to a broad variety of pathological examination specimens covering five cancer types.
Major findings of the preliminary application of QUAlu to clinical samples include: (1) all normal tissues displayed similar PUMA; (2) tumors showed variable PUMA with the highest levels in lung and colon and the lowest in thyroid cancer; (3) stools from colon cancer patients presented higher PUMA than those from control individuals; (4) lung squamous cell carcinomas showed higher PUMA than lung adenocarcinomas, and an increasing hypomethylation trend associated with smoking habits.
In conclusion, QUAlu is a simple and robust method to determine Alu hypomethylation in human biospecimens and may be easily implemented in research and clinical settings.RB was supported by a FPI fellowship from Ministerio de EconomĂa y Competitividad. AD-V was supported in part by a contract PTC2011-1091 from Ministerio de EconomĂa y Competitividad. This work was supported by grants from FEDER, the Ministerio de EconomĂa y Competitividad (SAF2011/23638 to MAP), the Instituto de Salud Carlos III (FIS PI11/02421 to JR, FIS PI11/01359 and FIS PI14/00240 to MR, FIS PI14/00308 to MJ, FIS PI12/00511 to MP), and FundaciĂł Olga Torres (to MJ)
FDG-PET-based neural correlates of Addenbrookeâs cognitive examination III scores in Alzheimerâs disease and frontotemporal degeneration
IntroductionThe Addenbrookeâs Cognitive Examination III (ACE-III) is a brief test useful for neuropsychological assessment. Several studies have validated the test for the diagnosis of Alzheimerâs disease (AD) and frontotemporal dementia (FTD). In this study, we aimed to examine the metabolic correlates associated with the performance of ACE-III in AD and behavioral variant FTD.MethodsWe enrolled 300 participants in a cross-sectional study, including 180 patients with AD, 60 with behavioral FTD (bvFTD), and 60 controls. An 18F-Fluorodeoxyglucose positron emission tomography study was performed in all cases. Correlation between the ACE-III and its domains (attention, memory, fluency, language, and visuospatial) with the brain metabolism was estimated.ResultsThe ACE-III showed distinct neural correlates in bvFTD and AD, effectively capturing the most relevant regions involved in these disorders. Neural correlates differed for each domain, especially in the case of bvFTD. Lower ACE-III scores were associated with more advanced stages in both disorders. The ACE-III exhibited high discrimination between bvFTD vs. HC, and between AD vs. HC. Additionally, it was sensitive to detect hypometabolism in brain regions associated with bvFTD and AD.ConclusionOur study contributes to the knowledge of the brain regions associated with ACE-III, thereby facilitating its interpretation, and highlighting its suitability for screening and monitoring. This study provides further validation of ACE-III in the context of AD and FTD
Detection of cerebrospinal fluid biomarkers changes of Alzheimerâs disease using a cognitive stress test in persons with subjective cognitive decline and mild cognitive impairment
IntroductionTimely and accurate diagnosis of the earliest manifestations of Alzheimerâs disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI).MethodsOne hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (AÎČ1-42/AÎČ1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated.ResultsLASSI-L scores were significantly associated with CSF biomarkers AÎČ1-42/AÎČ1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition.ConclusionOur study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD
Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System
Introduction: AQP4 (aquaporin-4)âimmunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4âIgG in cell differentiation. Material and Methods: We included three groupsâa group of patients with AQP4âIgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines. Results and Conclusions: The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative
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