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Multiple Sclerosis (Houndmills,... Mar 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM)....
BACKGROUND
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions.
OBJECTIVE
The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF).
METHODS
Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated.
RESULTS
A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06-0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34-0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19-0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07-0.33).
CONCLUSION
IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.
Topics: Humans; Child; Myelin-Oligodendrocyte Glycoprotein; Immunoglobulins, Intravenous; Retrospective Studies; Prednisone; Autoantibodies; Neoplasm Recurrence, Local; Mycophenolic Acid; Immunotherapy; Recurrence
PubMed: 38314479
DOI: 10.1177/13524585241226830 -
Brain Hemorrhages Sep 2023A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 in Wuhan, China. The new coronavirus disease... (Review)
Review
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 in Wuhan, China. The new coronavirus disease (COVID-19) was declared a global pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 can invade the nervous system aside from infecting the respiratory system as its primary target. The most common nervous system symptoms of COVID-19 are stated as headache, myalgia, fatigue, nausea, vomiting, sudden and unexplained anosmia, and ageusia. More severe conditions such as encephalomyelitis, acute myelitis, thromboembolic events, ischemic stroke, intracerebral hemorrhage, Guillain-Barré-syndrome, Bell's palsy, rhabdomyolysis, and even coma have also been reported. Cohort studies revealed that neurological findings are associated with higher morbidity and mortality. The neurological symptoms and manifestations caused by SARS-CoV-2 and COVID-19 are examined and summarized in this article.
PubMed: 36789140
DOI: 10.1016/j.hest.2023.02.001 -
Journal of Neuroimmunology Sep 2023Studies suggest that antinuclear antibodies (ANAs) may correlate with the long-term prognosis of Neuromyelitis optica spectrum disorder (NMOSD). In this study, we...
BACKGROUND
Studies suggest that antinuclear antibodies (ANAs) may correlate with the long-term prognosis of Neuromyelitis optica spectrum disorder (NMOSD). In this study, we investigated ANAs in Chinese patients with NMOSD and their relationship with disease outcomes.
METHODS
We retrospectively collected data from 525 patients diagnosed with NMOSD at West China Hospital between September 1, 2009, and October 1, 2021. Patients were classified into two groups: NMOSD with ANA (+) or without ANA (-). We compared the clinical characteristics, relapse rate, severe attacks, laboratory tests, Expanded Disability Status Scale (EDSS), and prognosis between the two groups.
RESULTS
Among the 525 NMOSD patients, those with ANA showed a higher frequency of AQP4-IgG (94.1% vs 79.3%, p < 0.001, false discovery rate (FDR) corrected p < 0.001), and anti-SSA (p < 0.001, FDR corrected p < 0.001), anti-SSB (p < 0.001, FDR corrected p < 0.001), anti-Ro52 antibodies (p < 0.001, FDR corrected p < 0.001), than those without ANA. ANA was detected in 403 patients during the acute phase. Patients with ANA (+) had higher EDSS scores in the acute stage (4.0 vs. 3.75, p = 0.013, FDR corrected p = 0.029) and at final follow-up (p = 0.032, FDR corrected p = 0.064). NMOSD patients with ANA (+) had a higher frequency of severe acute myelitis attack, severe acute myelitis and optic neuritis attack, motor and visual disability, compared to those with ANA (-) (42.1% vs. 27.8%, p = 0.001, FDR corrected p = 0.004, 19.3% vs. 10.3%, p = 0.004, FDR corrected p = 0.018, and 11.1% vs. 4.8%, p = 0.008, FDR corrected p = 0.022 respectively). The two groups had no significant difference in the annual recurrence rate (ARR).
CONCLUSION
ANA may be associated with more severe disease activity and disability in NMOSD.
Topics: Humans; Neuromyelitis Optica; Antibodies, Antinuclear; Retrospective Studies; Prognosis; Myelitis; Aquaporin 4; Autoantibodies
PubMed: 37453208
DOI: 10.1016/j.jneuroim.2023.578151 -
Journal of the Neurological Sciences Jul 2023Myelopathies require prompt etiologic diagnosis. We aimed to identify a specific myelopathy diagnosis in cases of suspected myelitis to highlight clinicoradiologic...
BACKGROUND
Myelopathies require prompt etiologic diagnosis. We aimed to identify a specific myelopathy diagnosis in cases of suspected myelitis to highlight clinicoradiologic differences.
METHODS
In this retrospective, single-centre cohort of subjects with suspected myelitis referred to London Multiple Sclerosis (MS) Clinic between 2006 and 2021, we identified those with MS and reviewed the remaining charts for etiologic diagnosis based on clinical, serologic, and imaging details.
RESULTS
Of 333 included subjects, 318/333 (95.5%) received an etiologic diagnosis. Most (274/333, 82%) had MS or clinically isolated syndrome. Spinal cord infarction (n = 10) was the commonest non-inflammatory myelitis mimic characterized by hyperacute decline (n = 10/10, 100%), antecedent claudication (n = 2/10, 20%), axial owl/snake eye (n = 7/9, 77%) and sagittal pencillike (n = 8/9, 89%) MRI patterns, vertebral artery occlusion/stenosis (n = 4/10, 40%), and concurrent acute cerebral infarct (n = 3/9, 33%). Longitudinal lesions were frequent in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (n = 7/7, 100%) and myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) (n = 6/7, 86%), accompanied by bright spotty (n = 5/7, 71%) and central-grey-restricted (n = 4/7, 57%) T2-lesions on axial sequences, respectively. Leptomeningeal (n = 4/4, 100%), dorsal subpial (n = 4/4, 100%) enhancement, and positive body PET/CT (n = 4/4, 100%) aided the diagnosis of sarcoidosis. Spondylotic myelopathies had chronic sensorimotor presentations (n = 4/6, 67%) with relative bladder sparing (n = 5/6, 83%), localizable to sites of disc herniation (n = 6/6, 100%). Metabolic myelopathies showed dorsal column or inverted 'V' sign (n = 2/3, 67%) MRI T2-abnormality with B12 deficiency.
CONCLUSIONS
Although no single feature reliably confirms or refutes a specific myelopathy diagnosis, this study highlights patterns that narrow the differential diagnosis of myelitis and facilitate early recognition of mimics.
Topics: Humans; Retrospective Studies; Positron Emission Tomography Computed Tomography; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Myelitis; Neuromyelitis Optica; Spinal Cord Diseases; Aquaporin 4; Immunoglobulin G
PubMed: 37207546
DOI: 10.1016/j.jns.2023.120677 -
Virulence Dec 2023Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which...
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients ( = 10), asymptomatic HTLV-1-infected carriers (ASP, = 8), and a second group of healthy controls ( = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.
Topics: Humans; Prognosis; Paraparesis, Tropical Spastic; Human T-lymphotropic virus 1; MicroRNAs; Biomarkers
PubMed: 37394816
DOI: 10.1080/21505594.2023.2230015 -
Journal of Clinical Virology : the... Dec 2023HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1...
BACKGROUND
HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease.
METHODS
We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic.
RESULTS
A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/10 PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence.
CONCLUSION
HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.
Topics: Middle Aged; Humans; Female; Paraparesis, Tropical Spastic; Spain; Leukocytes, Mononuclear; HTLV-I Infections; Human T-lymphotropic virus 1; Viral Load
PubMed: 38000189
DOI: 10.1016/j.jcv.2023.105619 -
BMJ (Clinical Research Ed.) Jul 2023
Topics: Humans; Pandemics; Poliomyelitis; Poliovirus
PubMed: 37468140
DOI: 10.1136/bmj.p1605 -
Ticks and Tick-borne Diseases Sep 2023In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To...
In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To clarify their roles, we have evaluated cerebrospinal fluid (CSF) count of the main lymphocyte populations (considered as a proxy of the brain parenchyma lymphocytic infiltrate) in TBE patients and analyzed if they associate with clinical presentation, blood-brain barrier disruption and intrathecal antibody synthesis. We have studied CSF from 96 adults with TBE (50 with meningitis, 40 with meningoencephalitis, 6 with meningoencephalomyelitis), 17 children and adolescents with TBE and 27 adults with non-TBE lymphocytic meningitis. Th CD3+CD4+, Tc CD3+CD8+, double positive T CD3+CD4+CD8+, B CD19+ and NK CD16+/56+ cells were counted cytometrically with a commercial fluorochrome-stained monoclonal antibody set. The associations between the counts and fractions of these cells and clinical parameters were analyzed with non-parametric tests, p<0.05 considered significant. The TBE patients had lower pleocytosis with similar proportions of the lymphocyte populations compared to non-TBE meningitis. The different lymphocyte populations correlated positively with one another, as well as with CSF albumin, IgG and IgM quotients. The higher pleocytosis and expansion of Th, Tc and B cells associated with a more severe disease and neurologic involvement: Th with encephalopathy, myelitis and weakly with cerebellar syndrome, Tc with myelitis and weakly with encephalopathy, B with myelitis and with at least moderately severe encephalopathy. The double-positive T lymphocytes associated with myelitis, but not with other forms of CNS involvement. The fraction of double positive T cells decreased in encephalopathy and the fraction of NK in patients with neurologic deficits. In children with TBE, Tc and B counts were increased at the expense of Th lymphocytes in comparison with adults. The concerted intrathecal immune response, involving the main lymphocyte populations, increases with the clinical severity of TBE, with no evidently protective or pathogenic elements distinguishable. However, the particular populations including B, Th and Tc cells associate with different, though overlapping, spectra of CNS manifestations, suggesting they may be specifically related to TBE manifesting as myelitis, encephalopathy and cerebellitis. The double-positive T and NK cells do not expand evidently with severity and may be most closely associated with the protective anti-TBEV response.
Topics: Adult; Child; Adolescent; Humans; Encephalitis, Tick-Borne; Leukocytosis; Lymphocytes; Myelitis; Brain Diseases
PubMed: 37245253
DOI: 10.1016/j.ttbdis.2023.102204 -
Frontiers in Immunology 2023Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral...
BACKGROUND AND OBJECTIVES
Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role in the development and progression of disease but can also be used as biomarkers. Here, we characterized immune signatures of EVPs from the cerebrospinal fluid (CSF) of individuals with HTLV-1-associated myelopathy (HAM), other chronic neurologic diseases, and healthy volunteers (HVs) to determine potential indicators of viral involvement and mechanisms of disease.
METHODS
We analyzed the EVPs from the CSF of HVs, individuals with HAM, HTLV-1-infected asymptomatic carriers (ACs), and from patients with a variety of chronic neurologic diseases of both known viral and non-viral etiologies to investigate the surface repertoires of CSF EVPs during disease.
RESULTS
Significant increases in CD8+ and CD2+ EVPs were found in HAM patient CSF samples compared to other clinical groups ( = 0.0002 and = 0.0003 compared to HVs, respectively, and = 0.001 and = 0.0228 compared to MS, respectively), consistent with the immunopathologically-mediated disease associated with CD8+ T-cells in the central nervous system (CNS) of HAM patients. Furthermore, CD8+ ( < 0.0001), CD2+ ( < 0.0001), CD44+ ( = 0.0176), and CD40+ ( = 0.0413) EVP signals were significantly increased in the CSF from individuals with viral infections compared to those without.
DISCUSSION
These data suggest that CD8+ and CD2+ CSF EVPs may be important as: 1) potential biomarkers and indicators of disease pathways for viral-mediated neurological diseases, particularly HAM, and 2) as possible meditators of the disease process in infected individuals.
Topics: Humans; Paraparesis, Tropical Spastic; Central Nervous System; Extracellular Vesicles; Nervous System Diseases; CD40 Antigens; Chronic Disease
PubMed: 37622115
DOI: 10.3389/fimmu.2023.1235791 -
Lupus Aug 2023Systemic lupus erythematosus-related transverse myelitis (SLE-TM) is a rare but serious complication of SLE, which may result in significant morbidity. Its incidence is... (Review)
Review
Systemic lupus erythematosus-related transverse myelitis (SLE-TM) is a rare but serious complication of SLE, which may result in significant morbidity. Its incidence is estimated between 0.5% and 1% of all SLE patients but may be the presenting feature in 30%-60% of these patients. Unfortunately, due to lack of high-quality studies, data regarding this condition remains limited. Its pathogenesis remains largely unknown and clinical presentation is variable. There are still no set guidelines regarding diagnosis, management, or monitoring and the role of autoantibodies remains controversial. In this review, we aim to summarize the available data regarding the epidemiology, pathogenesis, clinical features, management, and prognosis of this rare disease.
Topics: Humans; Lupus Erythematosus, Systemic; Myelitis, Transverse; Prognosis; Autoantibodies; Magnetic Resonance Imaging; Myelitis
PubMed: 37436429
DOI: 10.1177/09612033231185612