N2 in the time of COVID-19.
01 Sep 2020-Neuroimmunology and Neuroinflammation (Ovid Technologies (Wolters Kluwer Health))-Vol. 7, Iss: 5
TL;DR: This issue of Neurology® Neuroimmunology & Neuroinflammation reflects the impact of the CO VID-19 pandemic with 15 studies related to inflammatory or autoimmune neurologic complications in patients with this disease, including Guillain-Barré syndrome, CNS inflammatory disorders, and several studies addressing the risk of COVID-19 in Patients with neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS).
Abstract: This issue of Neurology ® Neuroimmunology & Neuroinflammation reflects the impact of the COVID-19 pandemic with 15 studies related to inflammatory or autoimmune neurologic complications in patients with this disease, including Guillain-Barre syndrome, CNS inflammatory disorders, and several studies addressing the risk of COVID-19 in patients with neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS) Among the latter, a study conducted in New York by Parotta et al1 included 72 patients with MS (55 relapsing and 17 progressive) or related disorders (4 patients) and confirmed (37 patients) or suspected COVID-19 illness Most patients did not require hospitalization despite being on disease-modifying therapies; factors associated with critical illness were similar to those of the general at-risk patient population On the other hand, most of the articles related to CNS disorders that occurred in association with COVID-19 are single cases describing acute necrotizing encephalitis or myelitis; acute disseminated encephalomyelitis; transient encephalitis with increased levels of interleukin 1 (IL1), IL6, and angiotensin-converting enzyme; and 2 cases of inflammatory vasculopathy (one of them with newly identified oligodendrocyte glycoprotein antibodies) Unrelated to the topic of the neurologic complications of COVID-19, the current issue of N2 contains multiple interesting studies, among which I selected 3 for additional comments
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TL;DR: In this article , the authors describe cases representing a diverse range of neurologic complications in patients infected with COVID-19, including stroke and other neurovascular complications, sequelae of critical illness and metabolic derangements, parainfectious inflammatory disorders, and poorly understood post-COVID syndrome.
Abstract: Abstract Since the first reported cases of pneumonia in December 2019, coronavirus disease 2019 (COVID-19) has rapidly become recognized as a multisystem illness, with known effects on virtually every organ system. In particular, neurologic complications of COVID-19 have been reported since the beginning of the pandemic in both ambulatory patients with mild disease and critically ill patients. Although it remains unclear whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has the potential to directly invade the central nervous system, strokes and other neurovascular complications, sequelae of critical illness and metabolic derangements, parainfectious inflammatory disorders, and a poorly understood post-COVID syndrome have all been reported in patients with COVID-19. Here, we describe cases representing a diverse range of neurologic complications in patients infected with COVID-19.
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TL;DR: Emerging data indicate that COVID-19 can trigger not only GBS but other autoimmune neurological diseases necessitating vigilance for early diagnosis and therapy initiation, and that patients with autoimmune neurological disease stable on common immunotherapies are facing increased risks of infection.
Abstract: 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.
184 citations
TL;DR: Most patients with MS with COVID-19 do not require hospitalization despite being on disease-modifying therapy, and no DMT class was associated with an increased risk of hospitalization or fatal outcome.
Abstract: Objective To report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness. Methods From March 16 to April 30, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records. Results We identified 76 patients (55 with relapsing MS, of which 9 had pediatric onset; 17 with progressive MS; and 4 with related disorders). Thirty-seven underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n = 34, 44.7%) and sphingosine-1-phosphate receptor modulators (n = 10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a nonambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome. Conclusions Most patients with MS with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at-risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.
128 citations
TL;DR: This study provides Class IV evidence that for children with AQP4-Ab NMOSD, all DMTs, particularly first-line rituximab, reduced the ARR and prevented further clinical relapses.
Abstract: Objective To describe the clinical phenotypes, treatment response, and outcome of children with antibodies against aquaporin-4 (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD).
Methods Retrospective, multicenter, and multinational study of patients with AQP4-Ab NMOSD aged <18 years at disease onset from a center in Brazil and 13 European centers. Data on demographics, clinical findings, and laboratory results were analyzed; calculation of annualized relapse rates (ARRs) pre- and on-treatment with disease-modifying therapies (DMTs) and of ORs for predictors of poor outcome was performed.
Results A total of 67 children were identified. At last follow-up (median 4 years, interquartile range 2–10 years), 37/67(57.8%) were found to have permanent disability. A more severe disease course was seen in the non-White ethnicity with both a shorter time to first relapse (p = 0.049) and a worse Expanded Disability Status Scale score at last follow-up (p = 0.008). The median ARR on treatment was 0.18 on azathioprine (n = 39, range 0–4), 0 on mycophenolate mofetil (n = 18, range 0–3), and 0 on rituximab (n = 29, range 0–2). No patient treated with rituximab as first-line therapy relapsed. Optic neuritis at onset was associated with a poor visual outcome below 20/200 (OR 8.669, 95% CI 1.764–42.616, p = 0.008), and a younger age at onset was associated with cognitive impairment (OR 0.786, 95% CI 0.644–0.959, p = 0.018).
Conclusions AQP4-Ab NMOSD in children is an aggressive disease with permanent disabilities observed in over half the cohort. All DMTs were associated with a reduction of ARR. First-line rituximab prevented further clinical relapses. International consensus on treatment protocols for children is required to reduce heterogeneity of treatment regimens used worldwide.
Classification of evidence This study provides Class IV evidence that for children with AQP4-Ab NMOSD, all DMTs, particularly first-line rituximab, reduced the ARR and prevented further clinical relapses.
34 citations
TL;DR: This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS and supports the association between CSF chitinase 3-like-1 levels and Neurologic disability according to EDSS scores in patientsWith PPMS.
Abstract: Objective To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS). Methods We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer9s instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up. Results Increasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118–0.742, p = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063–0.725, p = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999–1.017, p = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = −0.366, 95% CI -0.676–0.054, p = 0.086). There was no correlation with regard to NfL levels. Conclusions This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved. Classification of evidence This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.
19 citations
"N2 in the time of COVID-19." refers background in this paper
...In another study, Pérez-Miralles et al.(5) investigated the role of CSF chitinase 3-like-1 (CHI3L1), CHI3L2, and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS)....
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...In another study, Pérez-Miralles et al.5 investigated the role of CSF chitinase 3-like-1 (CHI3L1), CHI3L2, and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS)....
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TL;DR: To identify novel autoantibodies for neuropathic pain (NeP) with high specificity and high specificity, and to describe the mechanisms leading to NeP and their mechanisms of action.
Abstract: OBJECTIVE To identify novel autoantibodies for neuropathic pain (NeP). METHODS We screened autoantibodies that selectively bind to mouse unmyelinated C-fiber type dorsal root ganglion (DRG) neurons using tissue-based indirect immunofluorescence assays (IFA) with sera from 110 NeP patients with various inflammatory and allergic neurologic diseases or other neuropathies, and 50 controls without NeP including 20 healthy subjects and 30 patients with neurodegenerative diseases or systemic inflammatory diseases. IgG purified from IFA-positive patients' sera was subjected to Western blotting (WB) and immunoprecipitation (IP) using mouse DRG lysates. Immunoprecipitates were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify target autoantigens. RESULTS Antiunmyelinated C-fiber type DRG neuron antibodies were more frequent in patients with NeP than non-NeP subjects (10% vs 0%; p < 0.05). These autoantibodies were all from the IgG2 subclass and colocalized mostly with isolectin B4- and P2X3-positive pain-conducting small neurons but not with S100β-positive myelinated neurons. WB revealed a common immunoreactive band (approximately 220kDa). IP and LC-MS/MS studies identified plexin D1 as a target autoantigen. Immunoadsorption tests with recombinant human plexin D1 in IFA revealed that all 11 anti-small DRG neuron antibody-positive patients had anti-plexin D1 antibodies. Application of anti-plexin D1 antibody-positive patient sera to cultured DRG neurons increased membrane permeability, leading to cellular swelling. NeP patients with anti-plexin D1 antibodies commonly developed burning pain and current perception threshold abnormalities for C-fibers. Main comorbidities were atopy and collagen-vascular disease. Immunotherapies ameliorated NeP in 7 treated cases. INTERPRETATION Anti-plexin D1 antibodies are a novel biomarker for immunotherapy-responsive NeP. Ann Neurol 2018;84:208-224.
15 citations
"N2 in the time of COVID-19." refers background in this paper
...Plexin D1, which is a member of a family of transmembrane protein receptors that bind semaphorins as ligands.(4) Plexin D1 was found expressed in endothelial cells, immunocytes, muscle cells, and small dorsal root ganglia (DRG) neurons....
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...Patients with neuropathic pain and Plexin D1 antibodies frequently developed burning pain and thermal hyperalgesia along with sensory impairment, suggesting involvement of C-fiber type pain nerves and DRG neurons.(4) In the current study, the authors investigated 21 consecutive patients with IPTN and 35 controls with neuropathic pain....
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