心血管领域-心律失常方向

METHODS:BACKGROUND:The CNS manifestations of COVID-19 in children have primarily been described in case reports, which limit the ability to appreciate the full spectrum of the disease in paediatric patients. We aimed to identify enough cases that could be evaluated in aggregate to better understand the neuroimaging manifestations of COVID-19 in the paediatric population. METHODS:An international call for cases of children with encephalopathy related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and abnormal neuroimaging findings was made. Clinical history and associated plasma and cerebrospinal fluid data were requested. These data were reviewed by a central neuroradiology panel, a child neurologist, and a paediatric infectious diseases expert. The children were categorised on the basis of their time of probable exposure to SARS-CoV-2. In addition, cases were excluded when a direct link to SARS-CoV-2 infection could not be established or an established alternate diagnostic cause could be hypothesised. The accepted referral centre imaging data, from ten countries, were remotely reviewed by a central panel of five paediatric neuroradiologists and a consensus opinion obtained on the imaging findings. FINDINGS:38 children with neurological disease related to SARS-CoV-2 infection were identified from France (n=13), the UK (n=8), the USA (n=5), Brazil (n=4), Argentina (n=4), India (n=2), Peru (n=1), and Saudi Arabia (n=1). Recurring patterns of disease were identified, with neuroimaging abnormalities ranging from mild to severe. The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients). Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms. Splenial lesions (seven patients) and myositis (four patients) were predominantly observed in children with multisystem inflammatory syndrome. Cerebrovascular complications in children were less common than in adults. Significant pre-existing conditions were absent and most children had favourable outcomes. However, fatal atypical CNS co-infections developed in four previously healthy children infected with SARS-CoV-2. INTERPRETATION:Acute-phase and delayed-phase SARS-CoV-2-related CNS abnormalities are seen in children. Recurring patterns of disease and atypical neuroimaging manifestations can be found and should be recognised being as potentially due to SARS-CoV-2 infection as an underlying aetiological factor. Studies of paediatric specific cohorts are needed to better understand the effects of SARS-CoV-2 infection on the CNS at presentation and on long-term follow-up in children. FUNDING:American Society of Pediatric Neuroradiology, University of Manchester (Manchester, UK). VIDEO ABSTRACT.

METHODS:BACKGROUND:Leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1A) are involved in the pathogenesis of multiple sclerosis (MS) by affecting the inflammatory response and reactive oxygen species production. LEP rs7799039 and LEPR rs1137101 genetic variants modify the serum LEP levels and PGC1A rs8192678 alters the PGC1A activity. The study objective was to explore the associations of these variants with susceptibility to MS, disease course/clinical parameters and also with peripheral blood mononuclear cell expression of the target genes and plasma LEP concentrations, in the study subjects. METHODS:The study groups included 528 patients with MS and 429 controls. TaqMan® assays were used for genotyping and gene expression quantification. The Chi-square, parametric and nonparametric tests and simple/multiple logistic regression were performed for the statistical analysis of data. RESULTS:A multiple logistic regression model including all three investigated variants, applied to patients (RRMS + SPMS) and controls, showed that PGC1A rs8192678 minor allele had an increased risk for the occurrence of disease, with OR (95%CI) = 1,32 (1,01-1,73), P = 0,04. Between-effect of gender and LEPR variant on the multiple sclerosis severity score (MSSS) was identified (P = 0,005). In male patients (relapsing-remitting and secondary progressive), LEPR minor allele carriers had increased MSSS (GG + AG vs AA, median (minimum-maximum) = 5,38 (0,64-9,88) vs 4,27 (0,78-9,63); P = 0,01, Padj = 0,03). In relapsing-remitting patients LEP rs7799039 affected the LEP gene expression (P = 0,006; Padj = 0,04). CONCLUSION:The current findings implicate an impact of investigated genetic variants on the pathogenesis of MS.

METHODS:PURPOSE OF REVIEW:The COVID-19 pandemic has provided us with a unique opportunity to experiment with telehealth and evaluate its benefits and limitations. This review discusses the impact of telehealth on multiple sclerosis (MS) care and research in adults and children. RECENT FINDINGS:Telehealth visits for MS patients have been shown to reduce missed workdays and costs for patients. Brief telephone-based counseling may be associated with better adherence to disease-modifying therapy, although results of multiple home-based tele-rehabilitation for people with MS have been equivocal. Overall, patients and providers have reported high levels of satisfactions with telehealth. Several remote disability measures and numerous other technological tools have emerged for use in remote MS research and care. Major challenges of telehealth include limitations to performing a complete neurologic exam and disparities in access to telehealth amongst vulnerable populations with limited access to virtual platforms. Following the rapid expansion of telehealth during the pandemic, it is highly likely that we will continue to embrace the benefits of this valuable tool. Future directions for improving telehealth should include more evidence-based research on the diagnostic accuracy in neuroimmunology and reducing disparities in the access to telehealth.

METHODS:: This case of ascending paralysis, following an episode of diarrhea, was initially misinterpreted as Guillain-Barré syndrome. The prominent hypokalemia led to the search for other differential diagnoses, initially interpreted as a rare case of periodic hypokalemic paralysis, which usually occurs in Asians after intake of large amounts of starch foods, such as Spaghetti, or rest after heavy exercise. In this case, the reason for the hypokalemia with associated paralysis was caused by a hyperhyreosis factitia through denied intake of T3.

METHODS::The management of critical illness is especially challenging in low-resource environments, and early recognition and supportive care are essential, regardless of the ability to employ advanced or invasive therapy. In this report, we discuss two patients with Guillain-Barré syndrome who were managed successfully in the intensive care unit of a tertiary hospital in Malawi. Both patients recovered and were discharged home. The management and outcomes of these patients provide case-based lessons for improving intensive care unit medicine in low-resource contexts.

METHODS:INTRODUCTION:There are no many data on association between progression rate of Guillain-Barré syndrome (GBS) and disease outcome. AIM:The aim of our study was to analyze short-term outcome of GBS in relation to the rate of disease progression. METHODS:Our retrospective study included patients diagnosed with GBS in seven tertiary healthcare centers from 2009 to 2014. According to the rate of disease progression from onset of symptoms to the nadir, patients were divided in three groups: rapid-onset GBS (nadir reached in maximum 48 h), gradual-onset (nadir reached in three to 14 days), and slow-onset (nadir in 15 to 28 days). GBS disability scale (GDS) was used to assess functional disability at nadir and on discharge. RESULTS:Among 380 patients included in the study, 24 (6.3%) patients had rapid-onset, 274 (72.1%) gradual-onset, and 82 (21.6%) slow-onset GBS. Time from the onset of the disease to the hospital admission was much shorter in faster-onset forms (3.0 ± 4.1 days in rapid-onset vs. 6.8 ± 9.5 days in gradual-onset and 21.0 ± 9.6 days in slow-onset GBS, p < 0.01). Preceding events were less commonly identified in slow-onset forms. Patients with rapid-onset GBS were more likely to have axonal variants (p < 0.05). All three groups of patients were treated in a similar way, and there were no differences in GDS score at nadir (p > 0.05) and on discharge (p > 0.05) and no differences in the duration of hospital stay. CONCLUSION:Faster progression of GBS does not imply a poorer short-term functional outcome of the disease.

METHODS::Recent evidence suggested that neurological manifestations occur in patients with a severe form of coronavirus disease (COVID-19). On the basis of this issue, neurologists are very concerned about patients with neurological disorders, especially multiple sclerosis (MS), as consumers of immunosuppressive or immune-modulating drugs. Therefore, the administration of proper disease-modifying therapies (DMTs) in MS patients is critical during the pandemic status. On the one hand, both the autoimmune diseases and immunosuppressive drugs increase the risk of infection due to impairment in the immune system, and on the other hand, postponing of MS treatment has serious consequences on the central nervous system. In the present study, we discussed recent literature about the effect of DMTs administration on the severity of COVID-19 in the MS patients. Overall, it seems that DMTs do not provoke the COVID-19 infection in the MS patients by declining immune responses and cytokine storm. However, as a precaution, the supervision of a neurologist is highly recommended.

METHODS::Here we present a method for the simultaneous segmentation of white matter lesions and normal-appearing neuroanatomical structures from multi-contrast brain MRI scans of multiple sclerosis patients. The method integrates a novel model for white matter lesions into a previously validated generative model for whole-brain segmentation. By using separate models for the shape of anatomical structures and their appearance in MRI, the algorithm can adapt to data acquired with different scanners and imaging protocols without retraining. We validate the method using four disparate datasets, showing robust performance in white matter lesion segmentation while simultaneously segmenting dozens of other brain structures. We further demonstrate that the contrast-adaptive method can also be safely applied to MRI scans of healthy controls, and replicate previously documented atrophy patterns in deep gray matter structures in MS. The algorithm is publicly available as part of the open-source neuroimaging package FreeSurfer.

METHODS::The repair of inflamed, demyelinated lesions as in multiple sclerosis (MS) necessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch from a pro-inflammatory to an anti-inflammatory lesion environment. Subsequently, oligodendrocytes increase cholesterol levels as a prerequisite for synthesizing new myelin membranes. We hypothesized that lesion resolution is regulated by the fate of cholesterol from damaged myelin and oligodendroglial sterol synthesis. By integrating gene expression profiling, genetics and comprehensive phenotyping, we found that, paradoxically, sterol synthesis in myelin-phagocytosing microglia/macrophages determines the repair of acutely demyelinated lesions. Rather than producing cholesterol, microglia/macrophages synthesized desmosterol, the immediate cholesterol precursor. Desmosterol activated liver X receptor (LXR) signaling to resolve inflammation, creating a permissive environment for oligodendrocyte differentiation. Moreover, LXR target gene products facilitated the efflux of lipid and cholesterol from lipid-laden microglia/macrophages to support remyelination by oligodendrocytes. Consequently, pharmacological stimulation of sterol synthesis boosted the repair of demyelinated lesions, suggesting novel therapeutic strategies for myelin repair in MS.

METHODS::The revised S2 guidelines for treatment of giant cell arteritis have recently been published. Glucocorticosteroids remain the standard first line treatment. For severe or relapsing courses of the disease, the IL‑6 antagonist tocilizumab, a potent antibody, is now available as a therapeutic option; however, how long this treatment should be continued after having achieved a stable remission remains a matter of discussion. For patients with a complicated course and a high risk of relapse, a continuous treatment would be the safest way; however, with a milder course of disease for approximately half of the patients, treatment without relapse can be discontinued again. ZUSAMMENFASSUNG:Gerade eben wurden die neuen S2-Leitlinien zur Behandlung der Riesenzellarteriitis publiziert. Weiterhin bleibt die Glukokortikosteroidtherapie Standardtherapie. Bei schwereren Verläufen und Rezidiven steht uns mit dem IL(Interleukin)-6-Antagonisten Tocilizumab eine potente Antikörpertherapie zur Verfügung. Wie lange diese Therapie nach Erreichen einer stabilen Remission allerdings fortgesetzt werden muss/soll, ist bis jetzt nicht geklärt. Bei komplikativen Verläufen und hohem Rezidivrisiko sollte eine Dauertherapie durchgeführt werden. Bei milderem Verlauf kann jedoch bei knapp der Hälfte der Patienten die Therapie ohne Rezidiv auch wieder beendet werden.