Sleep and Epilepsy: a Focused Review of Pathophysiology, Clinical Syndromes, Co-morbidities, and Therapy.
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ABSTRACT:
SUBMITTER: Moore JL
PROVIDER: S-EPMC8116418 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBesides reducing the quality of obstetric care, the direct impact of COVID-19 on pregnancy and postpartum is uncertain.ObjectiveTo evaluate the characteristics of pregnant women who died due to COVID-19.Search strategyCochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021.Selection criteriaStudies that compared deceased and survived pregnant women with COVID-19.Data collection and analysisRelevant data were extracted and tabulated. The primary outcome was maternal co-morbidity.Main resultsThirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41-4.36, I2 = 0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77-42.44, I2 = 94%) or asthma (RR 2.05, 95% CI 0.81-5.15, I2 = 0%). Overall, at least one severe co-morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77-2.89, I2 = 76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00-12.98, I2 = 56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23-1.48, I2 = 95%) or mechanical ventilation (RR 4.34, 95% CI 0.96-19.60, I2 = 58%).ConclusionCOVID-19 with at least one co-morbidity increases risk of intensive care and mortality.
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Project description:The clinical heterogeneity of the myelodysplastic syndromes (MDSs) relates to the recently discerned panoply of molecular abnormalities extant within this disease spectrum. Despite increasing recognition of these biologic abnormalities, very limited therapeutic options exist to exploit our increasing understanding of the molecular pathophysiology of MDS, with only 1 therapy (lenalidomide) particularly focused on a specific clinical patient subset (del(5q) cytogenetics) and 2 epigenetic modulators (azacitidine and decitabine) having been approved for treating these patients. This article will review the mutational and biologic landscape of these disorders, as well as the targeted therapeutics currently in clinical trials that are focused on attacking these features. Given the molecular complexity of these disorders and the limited repertoire of effective therapeutic agents, we will also discuss novel approaches attempting to determine potentially effective and personalized treatment options through complementary chemosensitivity and computerized signaling network screening for these disparate MDS patient subsets. Translational use of such resources, combined with the rapidly evolving next-generation molecular technologies, should prove useful in effectuating improved and more selective options for therapy.
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Project description:IntroductionObstructive sleep apnoea (OSA) is a multisystem, debilitating, chronic disorder of breathing during sleep, resulting in a relatively consistent pattern of cognitive deficits. More recently, it has been argued that those cognitive deficits, especially in middle-aged patients, may be driven by cardiovascular and metabolic comorbidities, rather than by distinct OSA-processes, such as are for example ensuing nocturnal intermittent hypoxaemia, oxidative stress, neuroinflammation, and sleep fragmentation.MethodsThus, we undertook to define cognitive performance in a group of 27 middle-aged male patients with untreated OSA, who had no concomitant comorbidities, compared with seven matched controls (AHI mean ± S.D.: 1.9 ± 1.4 events/h; mean age 34.0 ± 9.3 years; mean BMI 23.8 ± 2.3 kg/m2). Of the 27 patients, 16 had mild OSA (AHI mean ± S.D.:11.7 ± 4.0 events/h; mean age 42.6 ± 8.2 years; mean BMI 26.7 ± 4.1 kg/m2), and 11 severe OSA (AHI 41.8 ± 20.7 events/h; age: 46.9 ± 10.9 years, BMI: 28.0 ± 3.2 kg/m2).ResultsIn our patient cohort, we demonstrate poorer executive-functioning, visuospatial memory, and deficits in vigilance sustained attention, psychomotor and impulse control. Remarkably, we also report, for the first time, effects on social cognition in this group of male, middle-aged OSA patients.ConclusionOur findings suggest that distinct, OSA-driven processes may be sufficient for cognitive changes to occur as early as in middle age, in otherwise healthy individuals.
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Project description:Heart failure (HF) is a condition that carries a considerable burden of disability many now related to co-existing co-morbidities. The drive to find newer effective therapies targeting novel mechanisms has led to a recent emphasis on treating common co-morbidities that are clustered around contemporary HF patients. Here is renewed contemporary co-morbidities that until recently have received little attention but which are now subject of considerable interest and potential therapeutic advance. These include, diabetes, functional mitral regurgitation and sleep disordered breathing. These three contemporary co-morbidities that have recently been subject to major trial evaluation will be reviewed in this paper.
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Project description:Acute coronary syndromes (ACS) are frequently reported in patients with coronavirus disease 2019 (COVID-19) and may impact patient clinical course and mortality. Although the underlying pathogenesis remains unclear, several potential mechanisms have been hypothesized, including oxygen supply/demand imbalance, direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, and endothelial dysfunction. The severe hypoxic state, combined with other conditions frequently reported in COVID-19, namely sepsis, tachyarrhythmias, anemia, hypotension, and shock, can induce a myocardial damage due to the mismatch between oxygen supply and demand and results in type 2 myocardial infarction (MI). In addition, COVID-19 promotes atherosclerotic plaque instability and thrombus formation and may precipitate type 1 MI. Patients with severe disease often show decrease in platelets count, higher levels of d-dimer, ultralarge von Willebrand factor multimers, tissue factor, and prolongation of prothrombin time, which reflects a prothrombotic state. An endothelial dysfunction has been described as a consequence of the direct viral effects and of the hyperinflammatory environment. The expression of tissue factor, von Willebrand factor, thromboxane, and plasminogen activator inhibitor-1 promotes the prothrombotic status. In addition, endothelial cells generate superoxide anions, with enhanced local oxidative stress, and endothelin-1, which affects the vasodilator/vasoconstrictor balance and platelet aggregation. The optimal management of COVID-19 patients is a challenge both for logistic and clinical reasons. A deeper understanding of ACS pathophysiology may yield novel research insights and therapeutic perspectives in higher cardiovascular risk subjects with COVID-19.
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Project description:Epilepsy is a common neurologic disorder. The underlying pathological processes include synaptic strength, inflammation, ion channels, and apoptosis. Acting as epigenetic factors, non-coding RNAs (ncRNAs) participate in the regulation of pathophysiologic processes of epilepsy and are dysregulated during epileptogenesis. Aberrant expression of ncRNAs are observed in epilepsy patients and animal models of epilepsy. Furthermore, ncRNAs might also be used as biomarkers for diagnosis and the prognosis of treatment response in epilepsy. In this review, we will summarize the role of ncRNAs in the pathophysiology of epilepsy and the putative utilization of ncRNAs as diagnostic biomarkers and therapeutic targets.
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Project description:BackgroundThe emergence of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated recognition of microdeletions and microduplications as risk factors for both generalised and focal epilepsies. Furthermore, there is evidence that some microdeletions/duplications, such as the 15q13.3 deletion predispose to a range of neuropsychiatric disorders, including intellectual disability (ID), autism, schizophrenia and epilepsy. We hypothesised that array CGH would reveal relevant findings in an adult patient group with epilepsy and complex phenotypes.Methods82 patients (54 from the National Hospital for Neurology and Neurosurgery and 28 from King's College Hospital) with drug-resistant epilepsy and co-morbidities had array CGH. Separate clinicians ordered array CGH and separate platforms were used at the two sites.ResultsIn the two independent groups we identified copy number variants judged to be of pathogenic significance in 13.5% (7/52) and 20% (5/25) respectively, noting that slightly different selection criteria were used, giving an overall yield of 15.6%. Sixty-nine variants of unknown significance were also identified in the group from the National Hospital for Neurology and Neurosurgery and 5 from the King's College Hospital patient group.ConclusionWe conclude that array CGH be considered an important investigation in adults with complicated epilepsy and, at least at present for selected patients, should join the diagnostic repertoire of clinical history and examination, neuroimaging, electroencephalography and other indicated investigations in generating a more complete formulation of an individual's epilepsy.
| S-EPMC3526772 | biostudies-literature
Project description:BackgroundDuring the Coronavirus Disease-2019 (COVID-19) pandemic, several characteristics of COVID-19 patients, based on demographics, clinical symptoms, and the presence of comorbidities, were found to be associated with the complications developed. COVID-19 symptoms vary greatly and are more prominent with comorbid diseases. Therefore, the aim of this study to find the clinical characteristics and its association with different comorbidities.MethodsThis is a retrospective study that was performed on the data obtained from medical records of 3999 patients in Riyadh. Demographic data, clinical symptoms and comorbidities were noted on the day of hospital admission. Complications developed during the COVID -19 infection were observed.ResultsThe average age of patients were 49.55 years old. Fever was the most common symptom among the patients (85.85%), followed by cough (85.85%), and shortness of breath (83.25%). The most common comorbidities were diabetes mellitus (39.51%), hypertension (33.91%), and asthma (9.45%), with chronic rhinosinusitis being the least common (0.5%). Pneumonia affected 61.90% of the patients admitted to the hospital. Furthermore, 8.73% got acute respiratory distress syndrome (ARDS), and 7.25% acquired pneumonia and Acute ARDS simultaneously. Co-morbidities were significantly correlated with complications developed during COVID-19.ConclusionHypertension and diabetes mellitus were two of the most common symptoms observed. Clinical symptoms, comorbidities, and complications are higher in female patients compared to male patients and most of the patients' developed complications.
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Project description:The clinicopathologic heterogeneity of myelodysplastic syndromes (MDS) is driven by diverse, somatically acquired genetic abnormalities. Recent technological advances have enabled the identification of many new mutations, which have implicated novel pathways in MDS pathogenesis, including RNA splicing and epigenetic regulation of gene expression. Molecular abnormalities, either somatic point mutations or chromosomal lesions, can be identified in the vast majority of MDS cases and underlie specific disease phenotypes. As the full array of molecular abnormalities is characterized, genetic variables are likely to complement standard morphologic evaluation in future MDS classification schemes and risk models.
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Project description:BackgroundCo-morbidities of vertiginous diseases have so far not been investigated systematically. Thus, it is still unclear whether the different vertigo syndromes (e.g. benign paroxysmal positional vertigo (BPPV), Meniere's disease (MD), vestibular migraine and phobic vertigo (PPV)) have also different spectrums of co-morbidities.MethodsAll patients from a cohort of 131 participants were surveyed using a standardised questionnaire about the co-morbidities hypertension, diabetes mellitus, BMI (body mass index), migraine, other headache, and psychiatric diseases in general and the likelihood of a depression in particular.ResultsWe noted hypertension in 29.0% of the cohort, diabetes mellitus in 6.1%, migraine in 8.4%, other headache in 32.1%, psychiatric diseases in 16.0%, overweight and obesity in 33.6% and 13.7% respectively, as well as a clinical indication for depression in 15.9%.ConclusionIn general, we did not detect an increased prevalence of the co-morbidities diabetes mellitus, arterial hypertension, migraine, other headache and obesity compared to the general population. There was an increased prevalence of psychiatric co-morbidity in patients with PPV, and the prevalence of hypertension was elevated in patients with MD.
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