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Neurology(R) Neuroimmunology &... Sep 2024To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and...
OBJECTIVES
To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor.
METHODS
Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls.
RESULTS
Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples.
DISCUSSION
Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.
Topics: Humans; Male; Adult; Female; Child; Autoantibodies; Hypothalamic Diseases; Adolescent; Transcription Factors; Hypoventilation; Autonomic Nervous System Diseases; Obesity; Young Adult; Middle Aged; Child, Preschool; Syndrome
PubMed: 38917381
DOI: 10.1212/NXI.0000000000200276 -
Frontiers in Sociology 2024Postural orthostatic Tachycardia Syndrome (PoTS), sometimes also written as 'POTS', is a form of dysautonomia (dysfunction of the autonomic nervous system) and...
Postural orthostatic Tachycardia Syndrome (PoTS), sometimes also written as 'POTS', is a form of dysautonomia (dysfunction of the autonomic nervous system) and orthostatic intolerance (which causes symptoms to be worsened when standing). This paper explores the extant literature on the lived experiences of those living with PoTS in relation to interactions between patients and healthcare providers as well as interactions at the level of the individual between PoTSies and those around them. My title contains the word 'salty' because it can be used to describe the feeling of being frustrated, while also reflecting a specific dietary change recommended to many (but not all) PoTS patients when they are told to consume additional sodium to minimise symptoms. COVID-19 is thought to have led to an increased prevalence of PoTS so this topic is particularly relevant to contemporary discussions and debates. In this sociological article, I refer not only to existing research on the lived experiences of having PoTS but also that of other chronic illnesses when relevant. The following themes are explored through auto/biographical and theoretical analysis: Undiagnosed and Invalidated; (In)Visible; Impacts of Diagnosis; Recovery and Expectations; Community. Reflecting auto/biographically, I have included analysis of interactions related to my lived experiences of presyncope, COVID-19 and dysautonomia, as I have been diagnosed with PoTS myself, which is thought to have been significantly exacerbated by the COVID-19 virus. This research is sociological, rather than medical or psychological, and conclusions are drawn about what is known so far about the lived experiences of living with PoTS, as well as discussion about what remains unknown, as there is currently a paucity of research on the lived experiences of individuals with PoTS and its comorbidities.
PubMed: 38912309
DOI: 10.3389/fsoc.2024.1283695 -
Journal of Clinical Medicine Jun 2024The rising prevalence of cardiovascular disease underscores the growing significance of heart failure (HF). Pathophysiological insights into HF highlight the... (Review)
Review
The rising prevalence of cardiovascular disease underscores the growing significance of heart failure (HF). Pathophysiological insights into HF highlight the dysregulation of the autonomic nervous system (ANS), characterized by sympathetic overactivity and diminished vagal tone, impacting cardiovascular function. Heart rate recovery (HRR), a metric measuring the heart's ability to return to its baseline rate post-exertion, plays a crucial role in assessing cardiovascular health. Widely applied across various cardiovascular conditions including HF, coronary artery disease (CAD), and arterial hypertension (HTN), HRR quantifies the difference between peak and recovery heart rates. Given its association with elevated sympathetic tone and exercise, HRR provides valuable insights into the perspective of HF, beyond effort tolerance, reaching toward prognostic and mortality indicators. Incorporating HRR into cardiovascular evaluations enhances our understanding of autonomic regulation in HF, offering potential implications for prognostication and patient management. This review addresses the significance of HRR in HF assessment, analyzing recently conducted studies, and providing a foundation for further research and clinical application.
PubMed: 38893039
DOI: 10.3390/jcm13113328 -
International Journal of Molecular... Jun 2024The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays... (Review)
Review
The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays a key role in primary liver diseases. Until recently, however, the impact of nerves on cancer development, progression, and metastasis has been unappreciated. This review highlights recent advances in understanding neuroanatomical networks within solid organs and their mechanistic influence on organ function, specifically in the liver and liver cancer. We discuss the interaction between the autonomic nervous system, including sympathetic and parasympathetic nerves, and the liver. We also examine how sympathetic innervation affects metabolic functions and diseases like nonalcoholic fatty liver disease (NAFLD). We also delve into the neurobiology of the liver, the interplay between cancer and nerves, and the neural regulation of the immune response. We emphasize the influence of the neuroimmune axis in cancer progression and the potential of targeted interventions like neurolysis to improve cancer treatment outcomes, especially for hepatocellular carcinoma (HCC).
Topics: Humans; Liver Neoplasms; Neuroimmunomodulation; Animals; Carcinoma, Hepatocellular; Liver; Non-alcoholic Fatty Liver Disease; Autonomic Nervous System
PubMed: 38892423
DOI: 10.3390/ijms25116237 -
Open Heart Jun 2024Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for neurocardiogenic syncope beyond placebo remains uncertain.
METHODS
The primary endpoint was the risk ratio (RR) of spontaneously recurring syncope following any therapeutic intervention. We also examined the effect of blinding on treatment efficacy. We identified all randomised trials which evaluated the effect of any pharmacological, device-based or supportive intervention on patients with a history of syncope. A systematic search was conducted on Medline, Embase, PubMed databases and Cochrane Central Register for Controlled Trials from 1950 to 25 April 2023. Event rates, their RRs and 95% CIs were calculated, and a random-effects meta-analysis was conducted for each intervention. Data analysis was performed in R using RStudio.
RESULTS
We identified 47 eligible trials randomising 3518 patients. Blinded trials assessing syncope recurrence were neutral for beta blockers, fludrocortisone and conventional dual-chamber pacing but were favourable for selective serotonin reuptake inhibitors (SSRIs) (RR 0.40, 95% CI 0.26 to 0.63, p<0.001), midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and closed-loop stimulation (CLS) pacing (RR 0.15, 95% CI 0.07 to 0.35, p<0.001). Unblinded trials reported significant benefits for all therapy categories other than beta blockers and consistently showed larger benefits than blinded trials.
CONCLUSIONS
Under blinded conditions, SSRIs, midodrine and CLS pacing significantly reduced syncope recurrence. Future trials for syncope should be blinded to avoid overestimating treatment effects.
PROSPERO REGISTRATION NUMBER
CRD42022330148.
Topics: Humans; Syncope, Vasovagal; Randomized Controlled Trials as Topic; Treatment Outcome; Recurrence
PubMed: 38890128
DOI: 10.1136/openhrt-2024-002669 -
PloS One 2024Heart rate variability (HRV), an important marker of autonomic nervous system activity, is usually determined from electrocardiogram (ECG) recordings corrected for...
BACKGROUND
Heart rate variability (HRV), an important marker of autonomic nervous system activity, is usually determined from electrocardiogram (ECG) recordings corrected for extrasystoles and artifacts. Especially in large population-based studies, computer-based algorithms are used to determine RR intervals. The Modular ECG Analysis System MEANS is a widely used tool, especially in large studies. The aim of this study was therefore to evaluate MEANS for its ability to detect non-sinus ECG beats and artifacts and to compare HRV parameters in relation to ECG processing. Additionally, we analyzed how ECG processing affects the statistical association of HRV with cardiovascular disease (CVD) risk factors.
METHODS
20-min ECGs from 1,674 subjects of the population-based CARLA study were available for HRV analysis. All ECGs were processed with the ECG computer program MEANS. A reference standard was established by experienced clinicians who visually inspected the MEANS-processed ECGs and reclassified beats if necessary. HRV parameters were calculated for 5-minute segments selected from the original 20-minute ECG. The effects of misclassified typified normal beats on i) HRV calculation and ii) the associations of CVD risk factors (sex, age, diabetes, myocardial infarction) with HRV were modeled using linear regression.
RESULTS
Compared to the reference standard, MEANS correctly classified 99% of all beats. The averaged sensitivity of MEANS across all ECGs to detect non-sinus beats was 76% [95% CI: 74.1;78.5], but for supraventricular extrasystoles detection sensitivity dropped to 38% [95% CI: 36.8;38.5]. Time-domain parameters were less affected by false sinus beats than frequency parameters. Compared to the reference standard, MEANS resulted in a higher SDNN on average (mean absolute difference 1.4ms [95% CI: 1.0;1.7], relative 4.9%). Other HRV parameters were also overestimated as well (between 6.5 and 29%). The effect estimates for the association of CVD risk factors with HRV did not differ between the editing methods.
CONCLUSION
We have shown that the use of the automated MEANS algorithm may lead to an overestimation of HRV due to the misclassification of non-sinus beats, especially in frequency domain parameters. However, in population-based studies, this has no effect on the observed associations of HRV with risk factors, and therefore an automated ECG analyzing algorithm as MEANS can be recommended here for the determination of HRV parameters.
Topics: Humans; Heart Rate; Electrocardiography; Female; Male; Middle Aged; Aged; Cohort Studies; Algorithms; Cardiovascular Diseases; Risk Factors
PubMed: 38885223
DOI: 10.1371/journal.pone.0304893 -
Cureus May 2024Meningeal solitary fibrous tumors (SFTs) are a rare central nervous system neoplastic process, resulting in frequent misdiagnosis as meningioma prior to pathologic...
Meningeal solitary fibrous tumors (SFTs) are a rare central nervous system neoplastic process, resulting in frequent misdiagnosis as meningioma prior to pathologic analysis. Appropriate diagnosis is essential to lowering morbidity and mortality, as Grade II or III SFTs are aggressive neoplasms that possess metastatic potential. The existing data may suggest that intracranial SFTs primarily afflict those in their fourth through sixth decades of life. However, we present the case of a patient outside this demographic presenting with symptoms that we were unable to identify in any prior reports. A 21-year-old male in the United States Navy presented to the emergency department (ED) with a two-month history of progressive headaches, leading to nausea and emesis. The patient also endorsed a daily incidence of the same olfactory hallucination followed by several minutes of palpitations, flushing, and dizziness. His neurologic exam was unremarkable, but imaging in the ED revealed a large mass abutting the right medial sphenoid wing. The radiographic appearance of the mass with a dural tail led to a preoperative diagnosis of meningioma. However, pathologic analysis following gross total resection identified the mass as an SFT. A brief literature review complementary to this case underscored the high variability of intracranial SFT case presentations with a relative scarcity of epidemiologic data due to rarity. This review identified that it was common to initially diagnose SFTs as meningioma, similar to this particular case. This emphasizes the importance of an appropriate pathologic diagnosis. This case adds to the existing literature as anecdotal evidence of SFT occurring in a young patient and a unique symptom profile most notable for olfactory hallucination and dysautonomia as features of focal seizure.
PubMed: 38860106
DOI: 10.7759/cureus.60104 -
Acta Neuropathologica Communications Jun 2024Synucleinopathies are a group of neurodegenerative disorders characterized by the presence of misfolded α-Synuclein (αSyn) in the brain. These conditions manifest with...
Synucleinopathies are a group of neurodegenerative disorders characterized by the presence of misfolded α-Synuclein (αSyn) in the brain. These conditions manifest with diverse clinical and pathophysiological characteristics. This disease diversity is hypothesized to be driven by αSyn strains with differing biophysical properties, potentially influencing prion-type propagation and consequentially the progression of illness. Previously, we investigated this hypothesis by injecting brain lysate (seeds) from deceased individuals with various synucleinopathies or human recombinant αSyn preformed fibrils (PFFs) into transgenic mice overexpressing either wild type or A53T human αSyn. In the studies herein, we expanded on these experiments, utilizing a panel of antibodies specific for the major carboxyl-terminally truncated forms of αSyn (αSynΔC). These modified forms of αSyn are found enriched in human disease brains to inform on potential strain-specific proteolytic patterns. With monoclonal antibodies specific for human αSyn cleaved at residues 103, 114, 122, 125, and 129, we demonstrate that multiple system atrophy (MSA) seeds and PFFs induce differing neuroanatomical spread of αSyn pathology associated with host specific profiles. Overall, αSyn cleaved at residue 103 was most widely present in the induced pathological inclusions. Furthermore, αSynΔC-positive inclusions were present in astrocytes, but more frequently in activated microglia, with patterns dependent on host and inoculum. These findings support the hypothesis that synucleinopathy heterogeneity might stem from αSyn strains with unique biochemical properties that include proteolytic processing, which could result in dominant strain properties.
Topics: alpha-Synuclein; Animals; Humans; Mice, Transgenic; Mice; Brain; Disease Models, Animal; Synucleinopathies; Antibodies, Monoclonal; Multiple System Atrophy; Prions; Female
PubMed: 38858742
DOI: 10.1186/s40478-024-01805-z -
JAMA Network Open Jun 2024Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18...
IMPORTANCE
Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity.
OBJECTIVE
To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021.
EXPOSURE
Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke.
MAIN OUTCOMES AND MEASURES
The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition.
RESULTS
Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge.
CONCLUSIONS AND RELEVANCE
The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.
Topics: Humans; COVID-19; Child; Female; Male; Child, Preschool; Hospitalization; Adolescent; Prospective Studies; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Nervous System Diseases; Infant; Severity of Illness Index
PubMed: 38857050
DOI: 10.1001/jamanetworkopen.2024.14122 -
BioRxiv : the Preprint Server For... Jun 2024Recent research emphasizes the intricate interplay of genetics and epigenetics in neurological disorders, notably Multiple Sclerosis (MS) and Guillain-Barre Syndrome...
Recent research emphasizes the intricate interplay of genetics and epigenetics in neurological disorders, notably Multiple Sclerosis (MS) and Guillain-Barre Syndrome (GBS), both of which exhibit cardiovascular dysregulation, with GBS often featuring serious bradyarrhythmias requiring prompt recognition and treatment. While cardiovascular autonomic dysfunction in MS is typically less severe, orthostatic intolerance affects around half of MS patients. Their distinction lies in their autoimmune responses, MS is an autoimmune disease affecting the central nervous system, causes demyelination and axon damage, leading to cognitive, ocular, and musculoskeletal dysfunction. In contrast, GBS primarily affects the peripheral nervous system, resulting in paralysis and respiratory complications. Despite their differences, both diseases share environmental risk factors such as viral infections and Vitamin D deficiency. This study aims to explore shared gene expression pathways, functional annotations, and molecular pathways between MS and GBS to enhance diagnostics, pathogenesis understanding, and treatment strategies through molecular analysis techniques. Through the gene expression analysis, five significant genes were found UTS2, TNFSF10, GBP1, VCAN, FOS. Results shows that Common DEGs are linked to apoptosis, bacterial infections, and atherosclerosis. Molecular docking analysis suggests Aflatoxin B1 as a potential therapeutic compound due to its high binding affinity with common differentially expressed proteins.
PubMed: 38853933
DOI: 10.1101/2024.05.29.595759