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Frontiers in Psychiatry 2021Previous studies have identified differentially expressed microRNAs in autism spectrum disorder (ASD), however, results are discrepant. We aimed to systematically...
Systematic Review and Bioinformatic Analysis of microRNA Expression in Autism Spectrum Disorder Identifies Pathways Associated With Cancer, Metabolism, Cell Signaling, and Cell Adhesion.
Previous studies have identified differentially expressed microRNAs in autism spectrum disorder (ASD), however, results are discrepant. We aimed to systematically review this topic and perform bioinformatic analysis to identify genes and pathways associated with ASD miRNAs. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses, we searched the Web of Science, PubMed, Embase, Scopus, and OVID databases to identify all studies comparing microRNA expressions between ASD persons and non-ASD controls on May 11, 2020. We obtained ASD miRNA targets validated by experimental assays from miRTarBase and performed pathway enrichment analysis using Metascape and DIANA-miRPath v3. 0. Thirty-four studies were included in the systematic review. Among 285 altered miRNAs reported in these studies, 15 were consistently upregulated, 14 were consistently downregulated, and 39 were inconsistently dysregulated. The most frequently altered miRNAs including miR-23a-3p, miR-106b-5p, miR-146a-5p, miR-7-5p, miR-27a-3p, miR-181b-5p, miR-486-3p, and miR-451a. Subgroup analysis of tissues showed that miR-146a-5p, miR-155-5p, miR-1277-3p, miR-21-3p, miR-106b-5p, and miR-451a were consistently upregulated in brain tissues, while miR-4742-3p was consistently downregulated; miR-23b-3p, miR-483-5p, and miR-23a-3p were consistently upregulated in blood samples, while miR-15a-5p, miR-193a-5p, miR-20a-5p, miR-574-3p, miR-92a-3p, miR-3135a, and miR-103a-3p were consistently downregulated; miR-7-5p was consistently upregulated in saliva, miR-23a-3p and miR-32-5p were consistently downregulated. The altered ASD miRNAs identified in at least two independent studies were validated to target many autism risk genes. , and were the most frequent targets, and miR-92a-3p had the most target autism risk genes. Pathway enrichment analysis showed that ASD miRNAs are significantly involved in pathways associated with cancer, metabolism (notably Steroid biosynthesis, Fatty acid metabolism, Fatty acid biosynthesis, Lysine degradation, Biotin metabolism), cell cycle, cell signaling (especially Hippo, FoxO, TGF-beta, p53, Thyroid hormone, and Estrogen signaling pathway), adherens junction, extracellular matrix-receptor interaction, and Prion diseases. Altered miRNAs in ASD target autism risk genes and are involved in various ASD-related pathways, some of which are understudied and require further investigation.
PubMed: 34744804
DOI: 10.3389/fpsyt.2021.630876 -
Tremor and Other Hyperkinetic Movements... 2019Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described.
BACKGROUND
Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described.
METHODS
We performed a systematic review of case reports and case series of pathologically- and genetically confirmed prionopathies. Timing of symptom and movement disorder onset were documented. Continuous variables were compared between two groups using the Wilcoxon rank sum test and between multiple groups using Kruskal-Wallis test. Categorical variables were compared using Fisher's exact test.
RESULTS
A total of 324 cases were included in this analysis. Movement disorders were a common feature at the onset of symptoms in most prionopathies. Gait ataxia was present in more than half of cases in all types of prionopathies. The prevalence of limb ataxia (20%) and myoclonus (24%) was lower in Gerstmann-Sträussler-Scheinker disease compared to other prionopathies (p ≤ 0.004). Myoclonus was common but often a later feature in sporadic Creutzfeldt-Jakob disease (2 months before death). Chorea was uncommon but disproportionately prevalent in variant Creutzfeldt-Jakob disease (30% of cases; p < 0.001). In genetic Creutzfeldt-Jakob disease, E200K carriers exhibited gait and limb ataxia more often when compared to other mutation carriers.
DISCUSSION
Movement disorders are differentially present in the course of the various prionopathies. The movement phenomenology and appearance are associated with the type of prion disease and the genotype and likely reflect the underlying pattern of neurodegeneration. Reliance on myoclonus as a diagnostic feature of sporadic Creutzfeldt-Jakob disease may delay its recognition given its relatively late appearance in the disease course.
Topics: Humans; Movement Disorders; Mutation; Myoclonus; Prion Diseases
PubMed: 31871824
DOI: 10.7916/tohm.v0.712 -
The Neurologist Mar 2017Creutzfeldt-Jacob disease (CJD) is a human prion disease generally characterized by subacute changes in behavior and intellectual function, often followed by ataxia,... (Review)
Review
BACKGROUND
Creutzfeldt-Jacob disease (CJD) is a human prion disease generally characterized by subacute changes in behavior and intellectual function, often followed by ataxia, vision changes, and myoclonus. Ten percent of cases may present atypically, both symptomatically and in respect to initial investigations.
METHODS
We report a case of CJD mimicking acute stroke and review all similar cases in the magnetic resonance imaging era reported in English, identified through a PubMed and SCOPUS search.
RESULTS
A 68-year-old woman presented with an acute left parietal syndrome, initially referred as a left middle cerebral artery territory stroke. Structural imaging was unremarkable and focal electroencephalogram changes suggested nonconvulsive status epilepticus. Subsequent clinical progression, with the development of cortical high signal on diffusion-weighted imaging and positive 14-3-3 protein in the cerebrospinal fluid, confirmed a diagnosis of CJD. Review of the literature identified 14 further cases mimicking both anterior and posterior stroke syndromes.
CONCLUSIONS
CJD develops primarily within a population in whom stroke risk factors are common and represents a rare but important stroke mimic. Negative vascular imaging in elderly patients with apparent acute stroke syndromes should prompt diagnostic review including consideration of prion diseases.
Topics: Aged; Brain; Cognition Disorders; Creutzfeldt-Jakob Syndrome; Disease Progression; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Stroke
PubMed: 28248914
DOI: 10.1097/NRL.0000000000000107 -
Acta Neurologica Belgica Sep 2018Sporadic Creutzfeldt-Jakob disease (sCJD) is a human prion disease that is a relatively common differential diagnosis in dementia patients. Therefore it needs a good... (Review)
Review
A systematic review comparing the diagnostic value of 14-3-3 protein in the cerebrospinal fluid, RT-QuIC and RT-QuIC on nasal brushing in sporadic Creutzfeldt-Jakob disease.
BACKGROUND
Sporadic Creutzfeldt-Jakob disease (sCJD) is a human prion disease that is a relatively common differential diagnosis in dementia patients. Therefore it needs a good diagnostic tool. Brain autopsy is the golden standard for the diagnosis of CJD; however, a less invasive technique is 14-3-3 protein measurement in the cerebrospinal fluid (CSF). In this systematic review, we compared the diagnostic value of the 14-3-3 protein measurement to the newer RT-QuIC test and a variant of RT-QuIC where nasal brushing is used to collect the samples.
METHODS
The search via MeSH terms and quality assessment was carried out by two individual researchers.
RESULTS
In 14-3-3 and RT-QuIC the sensitivity was comparable, respectively, 88% and 86%. Specificity however was higher in RT-QuIC 99.5% compared to 80% in 14-3-3. Nasal brushing showed the best results with a sensitivity of 97% and a specificity of 100%.
CONCLUSION
Nasal brushing, despite being the best diagnostic tool according to the data, needs more study since there has only been a few studies regarding the technique. It is safe to say that due to the high specificity, RT-QuIC is superior to 14-3-3 testing.
Topics: 14-3-3 Proteins; Biomarkers; Brain; Creutzfeldt-Jakob Syndrome; Humans; Sensitivity and Specificity
PubMed: 30097826
DOI: 10.1007/s13760-018-0995-8 -
Frontiers in Neuroscience 2021Alzheimer's disease (AD) is a primary, progressive, neurodegenerative disorder. Many risk factors for the development of AD have been investigated, including nutrition....
Alzheimer's disease (AD) is a primary, progressive, neurodegenerative disorder. Many risk factors for the development of AD have been investigated, including nutrition. Although it has been proven that nutrition plays a role in AD, the precise mechanisms through which nutrition exerts its influence remain undefined. The object of this study is to address this issue by elucidating some of the mechanisms through which nutrition interacts with AD. This work is a qualitative systematic bibliographic review of the current literature searchable on various available databases, including PubMed, Web of Science, and Google Scholar. Our evidence comprises 31 articles selected after a systematic search process. Patients suffering with AD present a characteristic microbiome that promotes changes in microglia generating a proinflammatory state. Many similarities exist between AD and prion diseases, both in terms of symptoms and in the molecular mechanisms of pathogenesis. Changes in the composition of the gut microbiome due to dietary habits could be one of the environmental factors affecting the development of AD; however, this is probably not the only factor. Similarly, the mechanism for self-propagation of beta-amyloid seen in AD is similar to that seen in prions.
PubMed: 34489620
DOI: 10.3389/fnins.2021.677777 -
International Journal of Molecular... Mar 2020Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDs), presenting a broad range of symptoms from motor dysfunctions...
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDs), presenting a broad range of symptoms from motor dysfunctions to psychobehavioral manifestations. A common clinical course is the proteinopathy-induced neural dysfunction leading to anatomically corresponding neuropathies. However, current diagnostic criteria based on pathology and symptomatology are of little value for the sake of disease prevention and drug development. Overviewing the pathomechanism of NDs, this review incorporates systematic reviews on inflammatory cytokines and tryptophan metabolites kynurenines (KYNs) of human samples, to present an inferential method to explore potential links behind NDs. The results revealed increases of pro-inflammatory cytokines and neurotoxic KYNs in NDs, increases of anti-inflammatory cytokines in AD, PD, Huntington's disease (HD), Creutzfeldt-Jakob disease, and human immunodeficiency virus (HIV)-associated neurocognitive disorders, and decreases of neuromodulatory KYNs in AD, PD, and HD. The results reinforced a strong link between inflammation and neurotoxic KYNs, confirmed activation of adaptive immune response, and suggested a possible role in the decrease of neuromodulatory KYNs, all of which may contribute to the development of chronic low grade inflammation. Commonalities of multifactorial NDs were discussed to present a current limit of diagnostic criteria, a need for preclinical biomarkers, and an approach to search the initiation factors of NDs.
Topics: Alzheimer Disease; Anti-Inflammatory Agents; Biomarkers; Cytokines; Humans; Huntington Disease; Inflammation; Kynurenine; Neurodegenerative Diseases; Parkinson Disease; Reactive Oxygen Species; Tryptophan
PubMed: 32244523
DOI: 10.3390/ijms21072431 -
European Radiology Dec 2021To evaluate the diagnostic yield and performance of DWI in patients with sporadic CJD (sCJD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the diagnostic yield and performance of DWI in patients with sporadic CJD (sCJD).
METHODS
A systematic literature search of the MEDLINE and EMBASE databases was performed, since their inception up to July 28, 2020. Pooled diagnostic yield of diffusion-weighted imaging was calculated using DerSimonian-Laird random-effects model. Pooled diagnostic performance of DWI (sensitivity, specificity, and area under the curve) in diagnosing sCJD among patients with rapidly progressive dementia was calculated using a bivariate random-effects model. Subgroup analysis and meta-regression were performed.
RESULTS
Fifteen original articles with a total of 1144 patients with sCJD were included. The pooled diagnostic yield was 91% (95% confidence interval [CI], 86 to 94%); summary sensitivity, 91% (95% CI, 84 to 95%); and specificity, 97% (95% CI, 94 to 99%). The area under the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI, 0.97-0.99). Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on DWI followed by striatum, thalamus, and cerebellum. Subgroup analysis and meta-regression demonstrated significant heterogeneity among the studies associated with the reference standards used for diagnosis of sCJD.
CONCLUSIONS
DWI showed excellent diagnostic value in diagnosis of sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia. Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on diffusion-weighted imaging followed by striatum, thalamus, and cerebellum.
KEY POINTS
• The pooled diagnostic yield of diffusion-weighted imaging in sporadic Creutzfeldt-Jakob disease was 91%. • The diagnostic performance of diffusion-weighted imaging for predicting sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia was excellent, with pooled sensitivity, 91%, and specificity, 97%. • Simultaneous involvement in the neocortex and striatum was most commonly seen on diffusion-weighted imaging (60%), followed by the neocortex without striatum (30%), thalamus (21%), cerebellum (8%), and striatum without neocortex (7%).
Topics: Animals; Brain; Cattle; Creutzfeldt-Jakob Syndrome; Diffusion Magnetic Resonance Imaging; Encephalopathy, Bovine Spongiform; Humans; Magnetic Resonance Imaging; Thalamus
PubMed: 33982159
DOI: 10.1007/s00330-021-08031-4 -
Journal of Clinical Neuroscience :... Apr 2021The Heidenhain variant of Creutzfeld-Jakob disease (HvCJD) is a relentlessly progressive and fatal neurodegenerative disorder characterised by prominent visual features...
The Heidenhain variant of Creutzfeld-Jakob disease (HvCJD) is a relentlessly progressive and fatal neurodegenerative disorder characterised by prominent visual features early in its clinical course. However, seizures are uncommonly reported in HvCJD. The case history of a patient admitted to our institution with HvCJD and seizures is described followed by a systematic review of the association between HvCJD and seizures. A systematic search of the databases Medline, PubMed, and PsycInfo was conducted, from inception to November 2019, using keywords relating to 'Creutzfeldt-Jakob disease' and 'Heidenhain variant', to ascertain the frequency of seizures in HvCJD, as well as, seizure semiology and electrographic features. The Preferred Items Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the construction of this systematic review. All studies, including case reports of patients who met the diagnostic criteria for HvCJD where details pertaining to clinical presentation, imaging, biochemical and EEG findings were available were included. There were 46 articles reporting on a total of 73 patients. Seizures occurred in only four out of 73 cases (5.5%). The semiology of these seizures were focal motor seizures with or without secondary generalisation and occipital lobe seizures. Imaging and electrographic findings were most commonly abnormal in the posterior cerebral cortices (in particular the occipital and occipito-parietal regions). This systematic review suggests that seizures are uncommon in HvCJD despite the frequency of imaging and electrographic abnormalities in the posterior cerebral regions. A key limitation of this systematic review is the variability of publications in terms of incomplete reporting of clinical data, in particular potential under-reporting of seizures, as well as follow up, which may have contributed to the lower frequency of seizures reported in patients with HvCJD.
Topics: Creutzfeldt-Jakob Syndrome; Electroencephalography; Female; Genetic Variation; Humans; Magnetic Resonance Imaging; Middle Aged; Occipital Lobe; Parietal Lobe; Seizures
PubMed: 33436304
DOI: 10.1016/j.jocn.2020.10.002 -
Journal of Neuroimaging : Official... 2015Diagnosis of Creutzfeldt-Jakob disease during life can be challenging since the huge variability of the symptoms which can be observed, especially in its early stages,... (Review)
Review
Diagnosis of Creutzfeldt-Jakob disease during life can be challenging since the huge variability of the symptoms which can be observed, especially in its early stages, may simulate other common forms of dementia. In latest years, noninvasive techniques such as magnetic resonance, positron emission tomography, and single-photon emission tomography have been evaluated to help clinical neurologists to provide a definite diagnosis. We here provide a systematic review of the current knowledge of neuroimaging in CJD in order to establish the actual state of the art.
Topics: Brain; Creutzfeldt-Jakob Syndrome; Evidence-Based Medicine; Humans; Magnetic Resonance Imaging; Neuroimaging; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed
PubMed: 24593302
DOI: 10.1111/jon.12098 -
Cells Jan 2021Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS...
Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS cases are sporadic; nevertheless, reports of families and isolated individuals with genetically determined CBS have been reported. In this systematic review, we analyze the demographical, clinical, radiological, and anatomopathological features of genetically confirmed cases of CBS. A systematic search was performed using the PubMed, EMBASE, and Cochrane Library databases, included all publications in English from 1 January 1999 through 1 August 2020. We found forty publications with fifty-eight eligible cases. A second search for publications dealing with genetic risk factors for CBS led to the review of eight additional articles. was the most common gene involved in CBS, representing 28 out of 58 cases, followed by , and . A set of symptoms was shown to be significantly more common in -CBS patients, including visuospatial impairment, behavioral changes, aphasia, and language alterations. In addition, specific demographical, clinical, biochemical, and radiological features may suggest mutations in other genes. We suggest a diagnostic algorithm to help in identifying potential genetic cases of CBS in order to improve the diagnostic accuracy and to better understand the still poorly defined underlying pathogenetic process.
Topics: Age of Onset; Aged; Aphasia; C9orf72 Protein; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Language Disorders; Male; Mental Disorders; Middle Aged; Mutation; Neurodegenerative Diseases; Parkinsonian Disorders; Prion Proteins; Progranulins; Syndrome; Treatment Outcome; Vision Disorders; tau Proteins
PubMed: 33467748
DOI: 10.3390/cells10010171