One year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to summarize the frequency of neurologic manifestations reported in patients with COVID-19 and to investigate ...the association of these manifestations with disease severity and mortality.
We searched PubMed, Medline, Cochrane library, ClinicalTrials.gov, and EMBASE for studies from December 31, 2019, to December 15, 2020, enrolling consecutive patients with COVID-19 presenting with neurologic manifestations. Risk of bias was examined with the Joanna Briggs Institute scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% confidence intervals (CIs) were calculated for neurologic manifestations. Odds ratio (ORs) and 95% CIs were calculated to determine the association of neurologic manifestations with disease severity and mortality. Presence of heterogeneity was assessed with
, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.
Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 patients with COVID-19, 89% of whom were hospitalized. Forty-one neurologic manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurologic symptoms included fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%), and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurologic diagnosis (pooled prevalence 2%). In patients with COVID-19 ≥60 years of age, the pooled prevalence of acute confusion/delirium was 34%, and the presence of any neurologic manifestations in this age group was associated with mortality (OR 1.80, 95% CI 1.11-2.91).
Up to one-third of patients with COVID-19 analyzed in this review experienced at least 1 neurologic manifestation. One in 50 patients experienced stroke. In those >60 years of age, more than one-third had acute confusion/delirium; the presence of neurologic manifestations in this group was associated with nearly a doubling of mortality. Results must be interpreted with the limitations of observational studies and associated bias in mind.
PROSPERO CRD42020181867.
The 2015–2016 epidemic of Zika virus (ZIKV) in the Americas and the Caribbean was associated with an unprecedented burden of neurological disease among adults. Clinically, Guillain-Barre syndrome ...(GBS) predominated among regions affected by the ZIKV epidemic, but the spectrum of neurological disease in the adults appears broader as cases of encephalopathy, encephalitis, meningitis, myelitis, and seizures have also been reported. A para-infectious temporal profile of ZIKV-associated GBS (ZIKV-GBS) has been described in clinical studies, which may suggest a direct viral neuropathic effect. However, ZIKV neuropathogenesis has not yet been fully understood. Mechanisms for ZIKV-GBS and other neurological syndromes have been hypothesized, such as adaptive viral genetic changes, immunological interactions with other circulating flaviviruses, and host and factors. This review summarizes the current evidence on ZIKV-associated neurological complications in the adults.
The purpose of this study was to develop and optimize different processing, extraction, amplification, and sequencing methods for metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid ...(CSF) specimens. We applied mNGS to 10 CSF samples with known standard-of-care testing (SoC) results (8 positive and 2 negative). Each sample was subjected to nine different methods by varying the sample processing protocols (supernatant, pellet, neat CSF), sample pretreatment (with or without bead beating), and the requirement of nucleic acid amplification steps using DNA sequencing (DNASeq) (with or without whole-genome amplification WGA) and RNA sequencing (RNASeq) methods. Negative extraction controls (NECs) were used for each method variation (4/CSF sample). Host depletion (HD) was performed on a subset of samples. We correctly determined the pathogen in 7 of 8 positive samples by mNGS compared to SoC. The two negative samples were correctly interpreted as negative. The processing protocol applied to neat CSF specimens was found to be the most successful technique for all pathogen types. While bead beating introduced bias, we found it increased the detection yield of certain organism groups. WGA prior to DNASeq was beneficial for defining pathogens at the positive threshold, and a combined DNA and RNA approach yielded results with a higher confidence when detected by both methods. HD was required for detection of a low-level-positive enterovirus sample. We demonstrate that NECs are required for interpretation of these complex results and that it is important to understand the common contaminants introduced during mNGS. Optimizing mNGS requires the use of a combination of techniques to achieve the most sensitive, agnostic approach that nonetheless may be less sensitive than SoC tools.
The Guillain–Barré syndrome has been associated with Zika virus infection. In this report from Colombia, further evidence of the association is provided, as well as further characterization of the ...associated neurologic syndrome.
Zika virus (ZIKV), a mosquito-borne RNA flavivirus, has caused a major outbreak in the Americas that began in 2014.
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ZIKV infection manifests as a self-limited febrile syndrome associated with rash, conjunctivitis, and arthralgias.
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–
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In 2013 and 2014, an increase in the number of cases of the Guillain–Barré syndrome was observed during an outbreak of ZIKV infection in French Polynesia.
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,
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Recently, clusters of the Guillain–Barré syndrome and microcephaly have been spatially and temporally related to the current outbreak of ZIKV infection in the Americas.
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In Colombia, the government reported the first autochthonous case of ZIKV infection in October 2015. . . .
Prenatal infections have long been recognized as important, preventable causes of developmental disabilities. The list of pathogens that are recognized to have deleterious effects on fetal brain ...development continues to grow, most recently with the association between Zika virus (ZIKV) and microcephaly. To answer clinical questions in real time about the impact of a novel infection on developmental disabilities, an historical framework is key. The lessons learned from three historically important pathogens: rubella, cytomegalovirus, and ZIKV, and how these lessons are useful to approach emerging congenital infections are discussed in this review. Congenital infections are preventable causes of developmental disabilities and several public health approaches may be used to prevent prenatal infection. When they cannot be prevented, the sequelae of prenatal infection may be treatable.
What this paper adds
The list of prenatal infections associated with developmental disabilities continues to increase.
Lessons learned from rubella, cytomegalovirus, and Zika virus have implications for new pathogens.
Severity of illness in the mother does not correlate with severity of sequelae in the infant.
What this paper adds
The list of prenatal infections associated with developmental disabilities continues to increase.
Lessons learned from rubella, cytomegalovirus, and Zika virus have implications for new pathogens.
Severity of illness in the mother does not correlate with severity of sequelae in the infant.
Prenatal infections are preventable causes of neurodevelopmental disabilities. This graphic highlights opportunities for intervention in the community and in the individual, from preconception through gestation, the neonatal period and childhood, to prevent or mitigate these sequelae.
The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela of COVID-19 (PASC), can implicate ...persistent neurological complications in up to one third of patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood-brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.
Background:
Although spinal magnetic resonance imaging (MRI) findings of neuromyelitis optica (NMO) have been described, there is limited data available that help differentiate NMO from other causes ...of longitudinally extensive transverse myelitis (LETM).
Objective:
To investigate the spinal MRI findings of LETM that help differentiate NMO at the acute stage from multiple sclerosis (MS) and other causes of LETM.
Methods:
We enrolled 94 patients with LETM into our study. Bright spotty lesions (BSL), the lesion distribution and location were evaluated on axial T2-weighted images. Brainstem extension, cord expansion, T1 darkness and lesion enhancement were noted. We also reviewed the brain MRI of the patients during LETM.
Results:
Patients with NMO had a greater amount of BSL and T1 dark lesions (p < 0.001 and 0.003, respectively). The lesions in NMO patients were more likely to involve greater than one-half of the spinal cord’s cross-sectional area; to enhance and be centrally-located, or both centrally- and peripherally-located in the cord. Of the 62 available brain MRIs, 14 of the 27 whom were NMO patients had findings that may be specific to NMO.
Conclusions:
Certain spinal cord MRI features are more commonly seen in NMO patients and so obtaining brain MRI during LETM may support diagnosis.
Increasing evidence supports a critical role of T cells in neurodegeneration associated with acute and subacute brain inflammatory disorders. Granzyme B (GrB), released by activated T cells, is a ...cytotoxic proteinase which may induce perforin-independent neurotoxicity. Here, we studied the mechanism of perforin-independent GrB toxicity by treating primary cultured human neuronal cells with recombinant GrB. GrBactivated the protease-activated receptor (PAR)-1 receptor on the neuronal cell surface leading to decreased intracellular cyclic AMP levels. This was followed by increased expression and translocation of the voltage gated potassium channel, Kv1.3 to the neuronal cell membrane. Similar expression of Kv1.3 was also seen in neurons of the cerebral cortex adjacent to active inflammatory lesions in patients with multiple sclerosis. Kv1.3 expression was followed by activation of Notch-1 resulting in neurotoxicity. Blocking PAR-1, Kv1.3 or Notch-1 activation using specific pharmacological inhibitors or siRNAs prevented GrB-induced neurotoxicity. Furthermore, clofazimine protected against GrB-induced neurotoxicity in rat hippocampus, in vivo. These observations indicate that GrB released from T cells induced neurotoxicity by interacting with the membrane bound Gi-coupled PAR-1 receptor and subsequently activated Kv1.3 and Notch-1. These pathways provide novel targets to treat T cell-mediated neuroinflammatory disorders. Kv1.3 is of particular interest since it is expressed on the cell surface, only under pathological circumstances, and early in the cascade of events making it an attractive therapeutic target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Zika virus (ZIKV) has caused a major infection outbreak in the Americas since 2015. In parallel with the ZIKV epidemic, an increase in cases of neurological disorders which include Guillain-Barré ...syndrome (GBS), encephalitis, and myelitis have been linked to the infection. We reviewed the evidence suggesting a relationship between ZIKV and neurological disorders in adults. A search of the literature supporting such link included databases such as PubMed and the World Health Organization (WHO) surveillance system. Through June 1, 2016, 761 publications were available on PubMed using the search word "Zika." Among those publications as well as surveillance reports released by the WHO and other health organizations, 20 articles linked ZIKV with neurological complications other than microcephaly. They corresponded to population and surveillance studies (
= 7), case reports (
= 9), case series (
= 3), and case-control studies (
= 1). Articles were also included if they provided information related to possible mechanisms of ZIKV neuropathogenesis. Evidence based on epidemiological and virological information supports the hypothesis that ZIKV infection is associated with GBS. Although cases of encephalopathy and myelitis have also been linked to ZIKV infection, the evidence is scarce and there is a need for virological, epidemiological, and controlled studies to better characterize such relationship.
Identifying the etiologic diagnosis in patients presenting with myelopathy is essential in order to guide appropriate treatment and follow-up. We set out to examine the etiologic diagnosis after ...comprehensive clinical evaluation and diagnostic work-up in a large cohort of patients referred to our specialized myelopathy clinic, and to explore the demographic profiles and symptomatic evolution of specific etiologic diagnoses.
In this retrospective study of patients referred to the Johns Hopkins Myelitis and Myelopathy Center between 2006 and 2021 for evaluation of "transverse myelitis", the final etiologic diagnosis determined after comprehensive evaluation in each patient was reviewed and validated. Demographic characteristics and temporal profile of symptom evolution were recorded.
Of 1193 included patients, 772 (65%) were determined to have an inflammatory myelopathy and 421 (35%) were determined to have a non-inflammatory myelopathy. Multiple sclerosis/clinically isolated syndrome (n = 221, 29%) and idiopathic myelitis (n = 149, 19%) were the most frequent inflammatory diagnoses, while spinal cord infarction (n = 197, 47%) and structural causes of myelopathy (n = 108, 26%) were the most frequent non-inflammatory diagnoses. Compared to patients with inflammatory myelopathies, patients with non-inflammatory myelopathies were more likely to be older, male and experience chronic symptom evolution (p < 0.001 for all). Hyperacute symptom evolution was most frequent in patients with spinal cord infarction (74%), while chronic symptom evolution was most frequent in patients with structural causes of myelopathy (81%), arteriovenous fistula or arteriovenous malformation (81%), myelopathy associated with rheumatologic disorder (71%), and sarcoidosis-associated myelopathy (61%).
Patients initially diagnosed with "transverse myelitis" are eventually found to have a more specific inflammatory or even non-inflammatory cause, potentially resulting in inappropriate treatment and follow-up. Demographic characteristics and temporal profile of symptom evolution may help inform a differential diagnosis in these patients. Etiological diagnosis of myelopathies would provide better therapeutic decisions.
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