心血管领域-心律失常方向

METHODS:OBJECTIVE:To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria. METHODS:From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis). RESULTS:The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS. CONCLUSION:The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity.

METHODS::1例急性淋巴细胞白血病患儿，规律化疗2年余，因“间断发热、走路不稳”收入郑州大学第一附属医院。头颅及脊髓磁共振成像提示多发白质脱髓鞘改变，脑脊液二代测序检测出巨细胞病毒，加用更昔洛韦及膦甲酸抗巨细胞病毒治疗后患儿体温恢复正常，意识好转，但患儿脱机困难，家属放弃治疗，出院后死亡。儿童巨细胞病毒感染相关急性播散性脑脊髓炎罕见，预后较差，抗巨细胞病毒治疗可能改变预后。.

METHODS::患儿 男，9岁7月龄，因“反复感染3年余，阵发性头痛3个月”就诊，临床表现为EB病毒感染后继发噬血细胞性淋巴组织增生症，反复肺炎，右侧额颞部头痛和头晕，发作性左下肢无力。精细分型提示成熟B细胞水平降低，自然杀伤细胞明显减少，免疫球蛋白水平降低。基因检测提示SH2D1A基因 c.163C>T（p.R55X）杂合变异。脑脊液中EB病毒DNA阳性，头颅磁共振成像提示脑白质损伤，头颅磁共振成像血管造影提示左前脑动脉有局部结节。诊断为X连锁淋巴细胞增殖性疾病1型，经干细胞移植该患儿脑血管炎、颅内EB病毒感染症状以及免疫功能明显好转。.

METHODS:BACKGROUND:Inflammation is the body's immune system's fast coordinating response to irritants caused by pathogens, external injuries, and chemical or radiation effects. The nucleotidebinding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a critical component of the innate immune system. The dysfunction of NLRP3 inflammasome contributes to various pathogeneses of complex diseases, such as uncontrolled infection, autoimmune diseases, neurodegenerative diseases, and metabolic disorders. This review describes recent progress on the discovery of NLRP3 inflammasome inhibitors and their therapeutic potential. METHODS:Based on the mechanism of NLRP3 activation, several types of NLRP3 inhibitors are described and summarized according to their origins, structures, bioactivity, and mechanism of action. Structure-Activity Relationship (SAR) is also listed for different scaffolds, as well as effective pharmacophore. RESULTS:Over one-hundred papers were included in the review. The development of NLRP3 inhibitors has been described from the earliest glyburide in 2001 to the latest progress in 2019. Several series of inhibitors have been categorized, such as JC-series based on glyburide and BC-series based on 2APB. Many other small molecules such as NLRP3 inhibitors are also listed. SAR, application in related therapeutic models, and five different action mechanisms are described. CONCLUSION:The findings of this review confirmed the importance of developing NLRP3 inflammasome inhibitors. Various NLRP3 inhibitors have been discovered as effective therapeutic treatments for multiple diseases, such as type II diabetes, experimental autoimmune encephalomyelitis, stressrelated mood disorders, etc. The development of a full range of NLRP3 inflammasome inhibitors is still at its foundational phase. We are looking forward to the identification of inhibitory agents that provide the most potent therapeutic strategies and efficiently treat NLRP3 inflammasome-related inflammatory diseases.

METHODS::Numerous experimental and clinical studies have proven that the new severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has a tropism for the nervous system. The infection of the nervous system by SARS‑CoV‑2 can occur via the nasal route through trans‑synaptic pathways. Coronaviruses can infect neurons and glial cells through angiotensin‑converting enzyme 2 receptors or by endocytosis. The infection of the central nervous system accompanied by coronavirus disease 2019-related systemic inflammation leads to the impairment of the blood-brain barrier and triggers a neuroinflammatory response with reactive astrogliosis and microglial activation. In addition, brain stem cells are being damaged, which results in respiratory distress. Apart from typical symptoms of COVID‑19 associated with the involvement of the respiratory system, neurological manifestations such as headache, dizziness, myalgia, anosmia, ageusia, encephalopathy, encephalitis, stroke, epileptic seizures, rhabdomyolysis, and Guillain-Barré syndrome are related to SARS‑CoV‑2 infection. In this review, we focused on the currently known neurological manifestations of COVID‑19, which could be considered mainly in asymptomatic patients with COVID‑19 and, if noted, may limit the transmission of coronavirus infection.

METHODS::The differential diagnosis of chronic demyelinating polyneuropathy particularly includes inflammatory (CIDP) and hereditary causes. Using the example of a 63-year-old patient, we show the diagnostic procedure with conventional electrophysiological diagnostics and additionally by the use of proximal nerve conduction studies with high-voltage stimulation (HVS) and the direct morphological examination by high-resolution nerve ultrasound. In the present case, the focal accentuation of the changes in HVS and the equally pronounced focal thickening of the most affected ulnar nerve in ultrasound confirmed the diagnosis of CIDP instead of hereditary neuropathy. ZUSAMMENFASSUNG:Die Differenzialdiagnose chronischer, demyelinisierender Polyneuropathien umfasst insbesondere entzündliche und hereditäre Ursachen. Wir zeigen am Beispiel eines 63-jährigen Patienten das diagnostische Prozedere einerseits mit der konventionellen elektrophysiologischen Diagnostik, andererseits insbesondere die Ergänzung durch die proximale Neurographie mit Hochvoltstimulation (HVS) sowie die direkte morphologische Untersuchung durch die hochauflösende Nervensonographie (NS). Im vorliegenden Fall belegten die fokale Akzentuierung der Veränderungen in der HVS und die ausgeprägten, ebenso fokal betonten Verdickungen des am stärksten betroffenen N. ulnaris in der NS die Diagnose einer CIDP und sprachen gegen die Diagnose einer hereditären Neuropathie.

METHODS:BACKGROUND:People living with MS during COVID-19 are experiencing the disruptions of the pandemic and concerns that their health status may place them at greater risk for worse COVID-19 outcomes. OBJECTIVE:This study sought to understand how people living with MS in the United States experienced distress and perceived their COVID-19-related risk during the first surge of the pandemic. METHODS:This was a web-based, self-report survey of people with MS who were living in the United States during the early stage of COVID-19. Primary outcomes were depression, anxiety, and positive-affect and well-being. Participants (N = 491) also provided data on demographics, MS-related factors, COVID-19 factors, and psychological coping. RESULTS:Psychological distress was associated with age, psychological coping strategies, and having had symptoms consistent with COVID-19, but not with MS disease-related variables and COVID-19 risk factors. Perception of COVID-19-related risk was associated with age, MS disease severity, COVID-19-related factors, and anxiety. CONCLUSION:This study demonstrated that even during COVID-19, distress and risk perception are primarily driven by psychological factors, experiencing symptoms consistent with COVID-19 and age, with minimal contribution from individual differences in health status, providing an impetus for continued efforts to optimize psychological interventions for people living with MS.

METHODS::Multiple sclerosis (MS) itself and first-line disease modifying therapies do not increase the risk of contracting COVID-19. However, home isolation is likely to result in a significant decrease in participation in leisure time physical activities and an increase in sedentary behavior. Therefore, using an online cross-sectional survey we examined the impact of the COVID-19 epidemic on physical activity (PA) behavior and fitness level in an Israeli cohort of people with multiple sclerosis (PwMS). The survey PA questionnaire included 10 questions. Specifically, participants reported on whether, and to what extent, the pandemic conditions had altered their PA behavior. One hundred and twenty PwMS filled out the online survey, 78 were females with a mean age of 43.0 (S.D.=12.9) years. PA behavior during the pandemic demonstrated that 17.5% who were engaged in PA before the COVID-19 pandemic, ceased PA, 33.3% reduced their PA, 20.0% continued their PA as before, 18.3% increased their PA during the pandemic, and 10.8% did not perform any PA in the past and did not so during the pandemic. As for the patient's self-reported fitness level, 31.7% reported that their fitness level had decreased during the pandemic, 60.0% felt no change, and 8.3% reported an improvement. Our findings serve as a call of action for all professionals involved in MS management to address physical activity behavior in PwMS during the COVID-19 epidemic.

METHODS:BACKGROUND:The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients. OBJECTIVE:To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic. METHODS:Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed. RESULTS:We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive. CONCLUSION:Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.

METHODS::The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), who are frequently on long-term immunotherapies. Treatment with IVIg does not increase the risk of contracting COVID-19, and the IVIg administration may have a protective role. However, infusions can expose patients to an increased risk of contracting SARS-CoV-2 due to repeated access to Health Facilities. In this report we analyzed the short-term follow-up of CIDP patients who modified their chronic IVIg therapy during pandemic. About half of CIDP patients regularly treated with IVIg tried to stop treatment and about 10% shifted to SCIg. Forty-two percent of the patients who stopped the treatment reported a clinical deterioration after suspension and had to restart IVIg. This study demonstrated that in selected cases it is possible to successfully stop the chronic IVIg treatment, even in patients who have been treated for several years.