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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 -
Alzheimer's Research & Therapy Jun 2024Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as...
BACKGROUND
Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults.
METHODS
Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aβ, Aβ), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed.
RESULTS
All autonomic networks were positively associated with Aβ ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected.
CONCLUSION
The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aβ, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.
Topics: Humans; Female; Alzheimer Disease; Aged; Male; Biomarkers; Amyloid beta-Peptides; Magnetic Resonance Imaging; Brain; Peptide Fragments; Autonomic Nervous System; Glial Fibrillary Acidic Protein; Aged, 80 and over; Neurofilament Proteins; Autonomic Nervous System Diseases
PubMed: 38851772
DOI: 10.1186/s13195-024-01486-9 -
JAMA Internal Medicine Jun 2024There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC).
IMPORTANCE
There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC).
OBJECTIVE
To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms.
DESIGN, SETTING, AND PARTICIPANTS
This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration.
INTERVENTIONS
Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days.
MAIN OUTCOMES AND MEASURES
Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline.
RESULTS
Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade.
CONCLUSIONS AND RELEVANCE
The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05576662.
PubMed: 38848477
DOI: 10.1001/jamainternmed.2024.2007 -
Movement Disorders : Official Journal... Jun 2024Multiple system atrophy is a neurodegenerative disease with α-synuclein aggregation in glial cytoplasmic inclusions, leading to dysautonomia, parkinsonism, and...
BACKGROUND
Multiple system atrophy is a neurodegenerative disease with α-synuclein aggregation in glial cytoplasmic inclusions, leading to dysautonomia, parkinsonism, and cerebellar ataxia.
OBJECTIVE
The aim of this study was to validate the accuracy of the International Parkinson and Movement Disorder Society Multiple System Atrophy clinical diagnostic criteria, particularly considering the impact of the newly introduced brain magnetic resonance imaging (MRI) markers.
METHODS
Diagnostic accuracy of the clinical diagnostic criteria for multiple system atrophy was estimated retrospectively in autopsy-confirmed patients with multiple system atrophy, Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration.
RESULTS
We identified a total of 240 patients. Sensitivity of the clinically probable criteria was moderate at symptom onset but improved with disease duration (year 1: 9%, year 3: 39%, final ante mortem record: 77%), whereas their specificity remained consistently high (99%-100% throughout). Sensitivity of the clinically established criteria was low during the first 3 years (1%-9%), with mild improvement at the final ante mortem record (22%), whereas specificity remained high (99%-100% throughout). When MRI features were excluded from the clinically established criteria, their sensitivity increased considerably (year 1: 3%, year 3: 22%, final ante mortem record: 48%), and their specificity was not compromised (99%-100% throughout).
CONCLUSIONS
The International Parkinson and Movement Disorder Society multiple system atrophy diagnostic criteria showed consistently high specificity and low to moderate sensitivity throughout the disease course. The MRI markers for the clinically established criteria reduced their sensitivity without improving specificity. Combining clinically probable and clinically established criteria, but disregarding MRI features, yielded the best sensitivity with excellent specificity and may be most appropriate to select patients for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PubMed: 38847384
DOI: 10.1002/mds.29879 -
Frontiers in Neuroscience 2024Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS)....
BACKGROUND
Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance.
METHODS
We measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects.
RESULTS
30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV.
CONCLUSION
30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.
PubMed: 38846714
DOI: 10.3389/fnins.2024.1367266 -
Cureus May 2024The anti-CASPR2 antibody-associated syndrome is a rare immune-mediated disorder. Most case reports describe neurologic symptoms that include encephalic signs,...
The anti-CASPR2 antibody-associated syndrome is a rare immune-mediated disorder. Most case reports describe neurologic symptoms that include encephalic signs, peripheral nerve hyperexcitability, dysautonomia, or neuropathic pain. We report the case of a 70-year-old man, admitted to the emergency department with complaints of slurred speech and imbalance. Neurological examination was relevant for dysarthria, hyperreflexia, and pancerebellar syndrome. Cranial CT and basic laboratory tests were normal and he spontaneously recovered after 14 hours. Over the next four months, the patient experienced three similar episodes in relation to stressful events (emotional and organic disturbances like prolonged fasting and vaccination). A contrast-enhanced MRI was performed, along with extensive laboratory testing, analysis of cerebrospinal fluid (CSF), paraneoplastic investigation, and next-generation sequencing panel for episodic ataxias. The results revealed oligoclonal bands in the CSF and positive anti-CASPR2 antibodies both in serum and CSF. Three-day-IV- methylprednisolone pulse followed by plasmapheresis and monthly intravenous immunoglobulins was performed with good response. In conclusion, the neurological manifestations that led to the diagnosis of anti-CASPR2 antibody-associated syndrome were intermittent self-limiting episodes of ataxia, often triggered by concurrent stress-inducing factors. This case supports the aim of other authors to add paroxysmal cerebellar ataxia to the spectrum of the anti-CASPR2 antibody syndrome.
PubMed: 38846209
DOI: 10.7759/cureus.59821 -
Neurologia I Neurochirurgia Polska 2024
Topics: Humans; Flushing; Hypohidrosis; Autonomic Nervous System Diseases; Thermography; Male; Adult; Female
PubMed: 38845593
DOI: 10.5603/pjnns.100534 -
BMJ Open Jun 2024This planned scoping review aims to provide insight into current literature regarding perceived quality of life (QoL), functioning and participation of patients with...
Quality of life, functioning and participation of adult patients with an amputation following complex regional pain syndrome I or brachial plexus injury: a scoping review protocol.
INTRODUCTION
This planned scoping review aims to provide insight into current literature regarding perceived quality of life (QoL), functioning and participation of patients with upper limb amputations (ULA) because of therapy-resistant debilitating complex regional pain syndrome type I (CRPS-I) or brachial plexus injury (BPI). It is important to gain insight into these outcomes, so we can properly inform and select patients eligible for amputation.
METHODS AND ANALYSIS
Joanna Briggs Institute methodology for scoping reviews, Systematic Reviews and Meta-Analyses Scoping Reviews guidelines and Arksey and O'Malley's framework will be used. Studies regarding adult patients with either BPI or CRPS-I who underwent ULA will be considered for inclusion. Studies should include one or more of the following topics: QoL, functioning or participation and should be written in English, German or Dutch. Searches will be conducted in the Cochrane database, PubMed, EMBASE and Google Scholar. Search strings will be provided by a licenced librarian. All relevant literatures will be considered for inclusion, regardless of published date, in order to give a full scope of available literature. Studies will be selected first by title, then abstract and finally by full article by two reviewers who will discuss after every round. A third reviewer will make final decisions to reach consensus if needed. Data will be presented as brief summaries and in tables using a modified data extraction table.
ETHICS AND DISSEMINATION
No ethical approval is required since no original data will be collected. Results will be disseminated through publication in a peer-reviewed journal and presentations at (inter)national conferences.
Topics: Humans; Quality of Life; Amputation, Surgical; Brachial Plexus; Adult; Research Design; Reflex Sympathetic Dystrophy; Upper Extremity
PubMed: 38839383
DOI: 10.1136/bmjopen-2023-079393 -
Neurobiology of Disease Aug 2024Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of...
Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of α-syn accumulation in GCIs is unclear, in particular whether abnormal α-syn aggregates result from the abnormal elevation of endogenous α-syn expression in MSA or ingested from the neuronal source. Tubulin polymerization promoting protein (TPPP) has been reported to play a crucial role in developing GCI pathology. Here, the total cell body, nucleus, and cytoplasmic area density of SNCA and TPPP transcripts in neurons and oligodendrocytes with and without various α-syn pathologies in the pontine base in autopsy cases of MSA (n = 4) and controls (n = 2) were evaluated using RNAscope with immunofluorescence. Single-nucleus RNA-sequencing data for TPPP was evaluated using control frontal cortex (n = 3). SNCA and TPPP transcripts were present in the nucleus and cytoplasm of oligodendrocytes in both controls and diseased, with higher area density in GCIs and glial nuclear inclusions in MSA. Area densities of SNCA and TPPP transcripts were lower in neurons showing cytoplasmic inclusions in MSA. Indeed, TPPP transcripts were unexpectedly found in neurons, while the anti-TPPP antibody failed to detect immunoreactivity. Single-nucleus RNA-sequencing revealed significant TPPP transcript expression predominantly in oligodendrocytes, but also in excitatory and inhibitory neurons. This study addressed the unclear origin of accumulated α-syn in GCIs, proposing that the elevation of SNCA transcripts may supply templates for misfolded α-syn. In addition, the parallel behavior of TPPP and SNCA transcripts in GCI development highlights their potential synergistic contribution to inclusion formation. In conclusion, this study advances our understanding of MSA pathogenesis, offers insights into the dynamics of SNCA and TPPP transcripts in inclusion formation, and proposes regulating their transcripts for future molecular therapy to MSA.
Topics: alpha-Synuclein; Multiple System Atrophy; Humans; Oligodendroglia; Inclusion Bodies; Aged; Female; Male; Middle Aged; Nerve Tissue Proteins; Neurons; Aged, 80 and over
PubMed: 38839023
DOI: 10.1016/j.nbd.2024.106551