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神经领域-神经系统自身免疫性疾病方向
METHODS:BACKGROUND:Between January 2015 and August 2016, two epidemic waves of Zika virus (ZIKV) disease swept the Northeastern (NE) region of Brazil. As a result, two waves of Guillain-Barré Syndrome (GBS) were observed concurrently. The mandatory reporting of ZIKV disease began region-wide in February 2016, and it is believed that ZIKV cases were significantly under-reported before that. The changing reporting rate has made it difficult to estimate the ZIKV infection attack rate, and studies in the literature vary widely from 17% to > 50%. The same applies to other key epidemiological parameters. In contrast, the diagnosis and reporting of GBS cases were reasonably reliable given the severity and easy recognition of the disease symptoms. In this paper, we aim to estimate the real number of ZIKV cases (i.e., the infection attack rate) and their dynamics in time, by scaling up from GBS surveillance data in NE Brazil. METHODOLOGY:A mathematical compartmental model is constructed that makes it possible to infer the true epidemic dynamics of ZIKV cases based on surveillance data of excess GBS cases. The model includes the possibility that asymptomatic ZIKV cases are infectious. The model is fitted to the GBS surveillance data and the key epidemiological parameters are inferred by using a plug-and-play likelihood-based estimation. We make use of regional weather data to determine possible climate-driven impacts on the reproductive number [Formula: see text], and to infer the true ZIKV epidemic dynamics. FINDINGS AND CONCLUSIONS:The GBS surveillance data can be used to study ZIKV epidemics and may be appropriate when ZIKV reporting rates are not well understood. The overall infection attack rate (IAR) of ZIKV is estimated to be 24.1% (95% confidence interval: 17.1%-29.3%) of the population. By examining various asymptomatic scenarios, the IAR is likely to be lower than 33% over the two ZIKV waves. The risk rate from symptomatic ZIKV infection to develop GBS was estimated as ρ = 0.0061% (95% CI: 0.0050%-0.0086%) which is significantly less than current estimates. We found a positive association between local temperature and the basic reproduction number, [Formula: see text]. Our analysis revealed that asymptomatic infections affect the estimation of ZIKV epidemics and need to also be carefully considered in related modelling studies. According to the estimated effective reproduction number and population wide susceptibility, we comment that a ZIKV outbreak would be unlikely in NE Brazil in the near future.
METHODS:BACKGROUND:Several studies have identified changes in the spinal cord DTI measurements in patients with multiple sclerosis (MS). However, correlations between changes in DTI parameters in normal appearing cervical spine and neurological findings have not been clearly established. OBJECTIVES:To determine whether diffusion tensor imaging (DTI) measurements such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are sufficiently sensitive in detecting microstructure alterations in normal-appearing spinal cords in patients with MS and whether they reflect these patients' clinical disability. MATERIAL AND METHODS:Fifteen patients diagnosed with relapsing-remitting MS (RRMS) with normal-appearing cervical spinal cords on plain MRI and 11 asymptomatic volunteers were enrolled in the study. Overall, 75 cervical spinal segments were analyzed. The regions of interest were drawn from the entire spinal cord cross-section and in the normal-appearing white matter tracts: the superior and inferior cerebellar peduncles and the posterior limbs of the internal capsules. Neurological deficit and the level of disability were evaluated using the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (T25FW) and the 9-hole peg test (9HPT) for manual dexterity. RESULTS:A significant difference (p < 0.05) in FA values between patients with MS and the control group was found at levels C2 (p = 0.047) and C3 (p = 0.023). No significant changes in ADC values were found. There was correlation between FA and ADC values in selected white matter tracts and at particular spinal cord levels. We also observed significant correlations between diffusion tensor imaging parameters and manual dexterity. CONCLUSIONS:Our preliminary results may suggest that the spinal cord's structural loss is the dominant factor in the inflammatory/demyelinating component in patients with MS. Diffusion tensor imaging changes in the spinal cord correlate with brain DTI changes. Manual functioning seems to be more affected than walking.
METHODS::Facing the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to find protective or curable drugs to prevent or to stop the course of the coronavirus SARS-CoV-2 infection. Recent evidence accumulates that adamantanes, widely used in different neurological diseases, could be repurposed for COVID-19. We hereby report on a questionnaire-based study performed to assess severity of COVID-19 in patients suffering from multiple sclerosis (n=10), Parkinson's disease (n=5) or cognitive impairment (n=7). In all patients infection with SARS-CoV-2 was confirmed by rtPCR of nasopharyngeal swabs. They were receiving treatment with either amantadine (n=15) or memantine (n=7) in stable registered doses. All of them had two-week quarantine since documented exposure and none of them developed clinical manifestations of infectious disease. They also did not report any significant changes in neurological status in the course of primary nervous system disease. Above results warrant further studies on protective effects of adamantanes against COVID-19 manifestation, especially in subjects suffering from neurological disease.
METHODS::Acute demyelinating inflammatory polyneuropathy (AIDP) is the most common type of Guillain-Barré syndrome (GBS) in Europe, following several viral and bacterial infections. Data on AIDP-patients associated with SARS-CoV-2 (coronavirus-2) infection are scarce. We describe the case of a 54-years-old Caucasian female patient with typical clinical and electrophysiological manifestations of AIDP, who was reported positive with PCR for SARS-CoV-2, 3 weeks prior to onset of the neurological symptoms. She did not experience a preceding fever or respiratory symptoms, but a transient loss of smell and taste. At the admission to our neurological department, a progressive proximally pronounced paraparesis, areflexia, and sensory loss with tingling of all extremities were found, which began 10 days before. The modified Erasmus Giullain-Barré Syndrome outcome score (mEGOS) was 3/9 at admission and 1/12 at day 7 of hospitalization. The electrophysiological assessment proved a segmental demyelinating polyneuropathy and cerebrospinal fluid examination showed an albuminocytologic dissociation. The neurological symptoms improved significantly during treatment with immunoglobulins. Our case draws attention to the occurrence of GBS also in patients with COVID-19 (coronavirus disease 2019), who did not experience respiratory or general symptoms. It emphasizes that SARS-CoV-2 induces immunological processes, regardless from the lack of prodromic symptoms. However, it is likely that there is a connection between the severity of the respiratory syndrome and further neurological consequences.
METHODS::Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy associated with dysimmune processes, often related to a previous infectious exposure. During Italian severe acute respiratory syndrome coronavirus-2 outbreak, a woman presented with a rapidly progressive flaccid paralysis with unilateral facial neuropathy after a few days of mild respiratory symptoms. Coronavirus was detected by nasopharyngeal swab, but there was no evidence of its presence in her cerebrospinal fluid, which confirmed the typical albumin-cytological dissociation of GBS, along with consistent neurophysiological data. Despite immunoglobulin infusions and intensive supportive care, her clinical picture worsened simultaneously both from the respiratory and neurological point of view, as if reflecting different aspects of the same systemic inflammatory response. Similar early complications have already been observed in patients with para-infectious GBS related to Zika virus, but pathological mechanisms have yet to be established.
METHODS:BACKGROUND:As a consequence of the coronavirus disease 2019 (COVID-19) pandemic, a large amount of consultations will be delivered through tele-medicine, especially for diseases causing chronic disability and requiring immunomodulatory treatments, such as multiple sclerosis (MS). METHODS:We have hereby reviewed available tools for tele-neurology examination in MS, including components of neurological examination that can be assessed through video, patient-reported outcome measures (PROMs), and digital technology. RESULTS:Overall, we have suggested a battery for assessing MS disability and relapses on tele-medicine, which brings together conventional examination, PROMs (e.g., Patient Determined Disease Steps, MS Impact Scale), and cognitive tests (Symbol Digit Modalities Test) that can be delivered remotely and in multiple languages. DISCUSSION:The use of common tools for neurological examination could improve tele-neurology practice for both general neurologists and MS specialists, and quality of care for people with MS.
METHODS:BACKGROUND:Hypermethylation of the growth hormone secretagogue receptor gene (GHSR) is increasingly observed in human cancers, suggesting that it could represent a pan-cancer biomarker of clinical interest. However, little is still known concerning GHSR methylation levels in thymic epithelial tumors, and particularly in thymomas from patients with Myasthenia Gravis (TAMG). MATERIAL AND METHODS:In the present study we collected DNA samples from circulating lymphocytes and surgically resected tumor tissues of 65 TAMG patients, and from the adjacent healthy thymic tissue available from 43 of them. We then investigated GHSR methylation levels in the collected tissues searching for correlation with the clinical characteristics of the samples. RESULTS:GHSR hypermethylation was observed in 18 thymoma samples (28%) compared to the healthy thymic tissues (P < 1 × 10-4), and those samples were particularly enriched in advanced disease stages than stage I (94% were in stage II or higher). GHSR was demethylated in the remaining 47 thymomas, as well as in all the investigated healthy thymic samples and in circulating lymphocytes. CONCLUSIONS:GHSR hypermethylation is not a pan-cancer marker or an early event in TAMG, but occurs in almost 1/4 of them and mainly from stage II onward. Subsequent studies are required to clarify the molecular pathways leading to GHSR hypermethylation in TAMG tissues and their relevance to disease progression.
METHODS::Vasculitides are a complex group of diseases sharing the defining feature of inflamed vessel walls. Vasculitides can be classified depending on the size of the predominantly affected vessels. Modern cross-sectional imaging methods have become a cornerstone in the diagnosis of vasculitis and may help in narrowing down differential diagnoses. This review presents the most important imaging modalities and typical findings in large and medium size vasculitis, implementing current imaging recommendations.
METHODS:OBJECTIVE:Disease-modifying drugs (DMDs) may alter the immune status and thus increase the susceptibility to coronavirus disease 2019 (COVID-19) in patients with MS or neuromyelitis optica spectrum disorders (NMOSD). However, evidence supporting this notion is currently lacking. In this study, we conducted a survey on the risk of COVID-19 in patients with MS and NMOSD. METHODS:The survey was conducted through the Chinese Medical Network for Neuroinflammation. Patients in 10 MS centers from 8 cities including Wuhan were included. Information about MS and NMOSD disease duration and the usage of DMDs were collected. Data of suspected cases of COVID-19 were obtained from hospital visits, questionnaires, and patient self-reporting. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed through clinical evaluation by a panel of experts in conjunction with chest CT and viral RNA detection. RESULTS:Eight hundred eighty-two of 1,804 (48.89%) patients with MS and 2,129 of 3,060 (69.58%) patients with NMOSD were receiving DMDs. There were no alterations in the patients' DMD regimen during January 15, 2020, to March 15, 2020, the 3-month period. None of the patients with MS treated with DMDs had COVID-19. However, 2 patients with relapsing NMOSD were diagnosed with COVID-19-related pneumonia. After treatment, both patients recovered from pneumonia and neither patient experienced new attacks due to predisposing SARS-CoV-2 infection in the following 2 months. CONCLUSIONS:No increased risk of COVID-19 infection was observed in patients with MS or NMOSD, irrespective of whether these patients received DMDs. A battery of stringent preventive measures adopted by neurologists to reduce COVID-19 infection in these patients may have contributed to low risk of COVID-19 infection.
METHODS:OBJECTIVE:To present the COVID-19-associated GBS, the prototypic viral-triggered autoimmune disease, in the context of other emerging COVID-19-triggered autoimmunities, and discuss potential concerns with ongoing neuroimmunotherapies. METHODS:Eleven GBS cases in four key COVID-19 hotspots are discussed regarding presenting symptoms, response to therapies and cross-reactivity of COVID spike proteins with nerve glycolipids. Emerging cases of COVID-19-triggered autoimmune necrotizing myositis (NAM) and encephalopathies are also reviewed in the context of viral invasion, autoimmunity and ongoing immunotherapies. RESULTS:Collective data indicate that in this pandemic any patient presenting with an acute paralytic disease-like GBS, encephalomyelitis or myositis-even without systemic symptoms, may represent the first manifestation of COVID-19. Anosmia, ageusia, other cranial neuropathies and lymphocytopenia are red flags enhancing early diagnostic suspicion. In Miller-Fisher Syndrome, ganglioside antibodies against GD1b, instead of QG1b, were found; because the COVID-19 spike protein also binds to sialic acid-containing glycoproteins for cell-entry and anti-GD1b antibodies typically cause ataxic neuropathy, cross-reactivity between COVID-19-bearing gangliosides and peripheral nerve glycolipids was addressed. Elevated Creatine Kinase (>10,000) is reported in 10% of COVID-19-infected patients; two such patients presented with painful muscle weakness responding to IVIg indicating that COVID-19-triggered NAM is an overlooked entity. Cases of acute necrotizing brainstem encephalitis, cranial neuropathies with leptomeningeal enhancement, and tumefactive postgadolinium-enhanced demyelinating lesions are now emerging with the need to explore neuroinvasion and autoimmunity. Concerns for modifications-if any-of chronic immunotherapies with steroids, mycophenolate, azathioprine, IVIg, and anti-B-cell agents were addressed; the role of complement in innate immunity to viral responses and anti-complement therapeutics (i.e. eculizumab) were reviewed. CONCLUSIONS:Emerging data indicate that COVID-19 can trigger not only GBS but other autoimmune neurological diseases necessitating vigilance for early diagnosis and therapy initiation. Although COVID-19 infection, like most other viruses, can potentially worsen patients with pre-existing autoimmunity, there is no evidence that patients with autoimmune neurological diseases stable on common immunotherapies are facing increased risks of infection.
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