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Rheumatology International Jul 2023Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a...
Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4 years and NMOSD onset was 43.2 ± 19.8 years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.
PubMed: 37500817
DOI: 10.1007/s00296-023-05397-0 -
Multiple Sclerosis and Related Disorders Jun 2021Spinal cord complications associated with coronavirus infectious disease of 2019 (COVID-19) are being widely reported. The purpose of this systematic review was to...
BACKGROUND
Spinal cord complications associated with coronavirus infectious disease of 2019 (COVID-19) are being widely reported. The purpose of this systematic review was to summarize so far available pieces of evidence documenting de novo novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) mediated spinal cord demyelinating diseases. Indeed, the spinal demyelinating disorders that have been reported in those patients who have suffered from COVID-19 rather than on the people already living with diagnosed or undiagnosed primary demyelinating disorders.
METHODS
We used the existing PRISMA consensus statement. Data were collected from PubMed, NIH Litcovid, EMBASE and Cochrane library databases, as well as Pre-print servers (medRxiv, bioRxiv, and pre-preints.org), until September 10, 2020, using pre-specified searching strategies.
RESULTS
The 21 selected articles were all case reports and included 11 (52%) men and 10 (48%) women. The mean age was of 46.7 ± 18.0. The neurological manifestations included weakness, sensory deficit, autonomic dysfunction and ataxia. In most cases, elevated cerebrospinal fluid protein as well as lymphocytic pleocytosis were found. SARS-CoV-2 was detected in five (24%) patients, meanwhile in 13 (62%) patients, the testing was negative. Testing was not performed in two cases and, in one, data were unavailable. Nearly half of the cases (N = 9) were associated with isolated long extensive transverse myelitis (LETM), whereas a combination of both LETM and patchy involvement was found in two. Only five patients had isolated short segment involvement and two patchy involvement. Furthermore, concomitant demyelination of both brain and spine was reported in six patients. Concerning the prognosis, most of the patients improved and the mortality rate was low (N = 2, <10%).
CONCLUSION
Spinal cord demyelination should be added to the plethora of immune mediated neurologic complications associated with COVID-19.
Topics: COVID-19; Communicable Diseases; Female; Humans; Male; Nervous System Diseases; SARS-CoV-2; Spinal Cord
PubMed: 33845350
DOI: 10.1016/j.msard.2021.102917 -
Multiple Sclerosis and Related Disorders Jul 2023Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks. However, little is known about the risk and the characteristics of attacks occurring after vaccination.
METHODS
We performed a systematic review and meta-analysis using PubMed and Embase databases to estimate a summary frequency of attacks occurring after vaccination and describe the clinical features of theses attacks. We defined attacks occurring after vaccination as typical NMOSD attacks that occurred up to 30 days after vaccine administration. For the frequency of attacks occurring after vaccination, we selected observational studies that reported the number of attacks and total number of patients that received vaccines; for the clinical description of the attacks, case reports and case series were also included.
RESULTS
We included 377 participants from 5 studies to estimate the frequency of NMOSD attacks occurring after vaccination. We found a summary frequency of of 2% (95% CI 1-4%, I = 0%). We evaluated 17 studies to identify that 13 different vaccines were associated with NMOSD attacks. A higher-than-expected proportion of males, simultaneous optic neuritis and transverse myelitis attacks, and anti-aquaporin 4 antibody negative cases were identified in vaccine-associated attacks from 24 participants from 17 studies. Nearly two-thirds of attacks occurring after vaccination were an initial event of NMOSD.
CONCLUSION
The frequency of NMOSD attacks occurring after vaccination is low and non-specific to different vaccine technologies. Our work reinforces the safety of vaccine recommendations in patients with NMOSD.
Topics: Male; Humans; Neuromyelitis Optica; Myelitis, Transverse; Optic Neuritis; Vaccination; Vaccines; Autoantibodies
PubMed: 37182477
DOI: 10.1016/j.msard.2023.104741 -
The Lancet. Infectious Diseases Oct 2019The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules.
METHODS
We did a random-effect meta-analysis with single proportions and a network meta-analysis in a Bayesian framework to synthesise direct and indirect data. We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials for randomised controlled trials published from Jan 1, 1980, to Nov 1, 2018, comparing poliovirus immunisation schedules in a primary series. Only trials done outside western Europe or North America and without variation in age schedules (ie, age at administration of the vaccine) between study groups were included in the analyses, because trials in high-income settings differ in vaccine immunogenicity and schedules from other settings and to ensure consistency within the network of trials. Data were extracted directly from the published reports. We assessed seroconversion against poliovirus serotypes 1, 2, and 3, and intestinal immunity against serotype 2, measured by absence of shedding poliovirus after a challenge OPV dose.
FINDINGS
We identified 437 unique studies; of them, 17 studies with a maximum of 8279 evaluable infants were eligible for assessment of humoral immunity, and eight studies with 4254 infants were eligible for intestinal immunity. For serotype 2, there was low between-trial heterogeneity in the data (τ=0·05, 95% credible interval [CrI] 0·009-0·15) and the risk ratio (RR) of seroconversion after three doses of bivalent OPVs was 0·14 (95% CrI 0·11-0·17) compared with three doses of trivalent OPVs. The addition of one or two full doses of an IPV after a bivalent OPV schedule increased the RR to 0·85 (0·75-1·0) and 1·1 (0·98-1·4). However, the addition of an IPV to bivalent OPV schedules did not significantly increase intestinal immunity (0·33, 0·18-0·61), compared with trivalent OPVs alone. For serotypes 1 and 3, there was susbstantial inconsistency and between-trial heterogeneity between direct and indirect effects, so we only present pooled estmates on seroconversion, which were at least 80% for serotype 1 and at least 88% for serotype 3 for all vaccine schedules.
INTERPRETATION
For WHO's polio eradication programme, the addition of one IPV dose for all birth cohorts should be prioritised to protect against paralysis caused by type 2 poliovirus; however, this inclusion will not prevent transmission or circulation in areas with faecal-oral transmission.
FUNDING
UK Medical Research Council.
Topics: Antibodies, Viral; Disease Eradication; Feces; Humans; Immunity, Humoral; Immunity, Mucosal; Immunization Schedule; Immunogenicity, Vaccine; Infant; Infant, Newborn; Intestinal Mucosa; Network Meta-Analysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Seroconversion; Serogroup; Vaccination; Virus Shedding
PubMed: 31350192
DOI: 10.1016/S1473-3099(19)30301-9 -
Frontiers in Neurology 2022Vaccinations provided the most effective tool to fight the SARS-CoV-2 pandemic. It is now well established that COVID-19 vaccines are safe for the general population;...
BACKGROUND
Vaccinations provided the most effective tool to fight the SARS-CoV-2 pandemic. It is now well established that COVID-19 vaccines are safe for the general population; however, some cases of rare adverse events following immunization have been described, including CNS Inflammatory Demyelinating Events (CIDEs). Although observational studies are showing that these events are rare and vaccines' benefits highly outweigh the risks, collecting and characterizing post-COVID-19 vaccine CIDEs might be relevant to single out potential risk factors and suggest possible underlying mechanisms.
METHODS
Here we describe six CIDEs, including two acute transverse myelitis (ATM), three multiple sclerosis (MS), and one neuromyelitis optica spectrum disorder (NMOSD), occurring between 8 and 35 days from a COVID-19 vaccine. Moreover, we performed a systematic literature search of post-COVID-19 vaccines CIDEs, including ATM, ADEM, MS, and NMOSD/MOGAD, published worldwide between December 2020 and December 2021, during 1 year of the vaccination campaign. Clinical/MRI and CSF/serum characteristics were extracted from reviewed studies and pooled-analyzed.
RESULTS
Forty-nine studies were included in the systematic review, reporting a total amount of 85 CIDEs. Considering our additional six cases, 91 CIDEs were summarized, including 24 ATM, 11 ADEM, 47 MS, and nine NMOSD/MOGAD. Overall, CIDEs occurred after both mRNA ( = 46), adenoviral-vectored ( = 37), and inactivated vaccines ( = 8). Adenoviral-vectored vaccines accounted for the majority of ADEM (55%) and NMOSD/MOGAD (56%), while mRNA vaccines were more frequent in MS new diagnoses (87%) and relapses (56%). Age was heterogeneous (19-88) and the female sex was prevalent. Time from vaccine to symptoms onset was notably variable: ADEM and NMOSD/MOGAD had a longer median time of onset (12.5 and 10 days) compared to ATM and MS (6 and 7 days) and further timing differences were observed between events following different vaccine types, with ATM and MS after mRNA-vaccines occurring earlier than those following adenoviral-vectored ones.
CONCLUSION
Both the prevalence of vaccine types for certain CIDEs and the heterogeneity in time of onset suggest that different mechanisms-with distinct dynamic/kinetic-might underly these events. While epidemiological studies have assessed the safety of COVID-19 vaccines, descriptions and pooled analyses of sporadic cases may still be valuable to gain insights into CIDE's pathophysiology.
PubMed: 36530641
DOI: 10.3389/fneur.2022.1018785 -
Journal of Neurovirology Feb 2022To verify brain and spinal changes using magnetic resonance imaging in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. This was a systematic... (Review)
Review
Cerebral and spinal cord changes observed through magnetic resonance imaging in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis: a systematic review.
To verify brain and spinal changes using magnetic resonance imaging in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. This was a systematic review. The descriptors used were tropical spastic paraparesis and magnetic resonance image. The keyword HTLV-1-associated myelopathy was also used. Twenty-three articles were included: 16 detected brain changes and 18 detected spinal changes. White matter lesions were the most frequent finding in the brain. Brain injuries were most frequently identified in the periventricular region, in the subcortical region, in the centrum semiovale, in the brain stem, and corpus callosum. Atrophy was the most frequent finding of the spinal cord, affecting the thoracic and cervical regions, and was associated with a longer evolution of myelopathy. White matter lesions in these regions were also observed. Cortical white matter lesions and thoracic spinal cord atrophy were the most frequently reported changes in patients with HTLV-1-associated myelopathy.
Topics: Atrophy; Brain; Human T-lymphotropic virus 1; Humans; Magnetic Resonance Imaging; Nervous System Diseases; Paraparesis, Tropical Spastic; Spinal Cord
PubMed: 34981435
DOI: 10.1007/s13365-021-01043-2 -
Journal of Neuroimmunology Mar 2022Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD) is neuroimmunological disorder manifesting as episodes of ADEM, optic... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of rituximab for relapse prevention in myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD): A systematic review and meta-analysis.
INTRODUCTION
Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD) is neuroimmunological disorder manifesting as episodes of ADEM, optic neuritis, transverse myelitis, brainstem encephalitis, and other CNS manifestations and notably, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Current treatment strategy is high-dose intravenous methylprednisolone followed by maintenance immunotherapy for relapse prevention. The purpose of this study is to systematically create compelling evidence addressing the role of rituximab in relapse prevention among patient with MOGAD.
METHODS
This study follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. We searched PubMed, Embase, and Google Scholar for English language papers published between 2010 and 2021. Individual study proportions were meta-analyzed to yield the pooled relapse-free patient proportion. Individual studies' mean pre- and post-treatment annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) were used to calculate the overall mean difference.
RESULTS
Our meta-analysis includes 13 studies with 238 subjects. After rituximab treatment, 55% (95% CI: 0.49-0.61) of MOGAD patients remained relapse-free. Our study found that after rituximab therapy, ARR was lowered by 1.36 (95% CI 1.02-1.71, p < 0.001). Similarly, we detected a 0.52 (95% CI: 0.08 to 0.96, p = 0.02) difference in EDSS score after starting rituximab medication. Because only a handful of the included studies documented adverse events, the safety profile of rituximab for the treatment of MOGAD could not be effectively determined.
CONCLUSION
Our meta-analysis shows that rituximab effectively prevents relapses in MOGAD patients.
Topics: Autoantibodies; Autoantigens; Demyelinating Autoimmune Diseases, CNS; Humans; Immunoglobulin G; Immunologic Factors; Myelin-Oligodendrocyte Glycoprotein; Recurrence; Rituximab
PubMed: 35063726
DOI: 10.1016/j.jneuroim.2022.577812 -
Medicine Sep 2023The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the...
BACKGROUND
The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the diseases which is gaining popularity these days and has been declared as public health emergency of international concern by the world health organization, is human monkeypox virus (HMPX). Proper understanding of the clinical spectrum of the disease is of paramount importance for early diagnosis and treatment. In this review, we aimed to study and quantify the neurological manifestations of HMPX virus infection.
METHODS
Any study, released prior to April 13, 2023, that reported neurological manifestations in patients infected by HMPX virus were reviewed systematically on PubMed, Scopus, Google Scholar, and Cochrane Library using the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) statement.
RESULTS
Our systematic review included data from 22 eligible studies: 10 cohort studies, 3 cross sectional studies, one retrospective study, 5 case series, and 2 case reports. The most commonly reported neurological manifestations of HMPX were headache (48.84%), myalgia (27.50%), fatigue (17.73%), and photophobia (4.43%). Uncommonly, HMPX can also present with visual deficit (0.57%), seizure (0.34%), encephalitis (0.8%), dizziness (0.34%), encephalomyelitis (0.23%), coma (0.11%), and transverse myelitis (0.11%).
DISCUSSIONS
Monkeypox virus usually presents with self-limiting painful rash, lymphadenitis, and fever, complications like secondary skin infection, eye problems and pneumonia can be life threatening, carrying a case fatality rate of 1% to 10%. Neurological manifestations are not uncommon and can further add-on to morbidity and mortality.
Topics: Humans; Coinfection; Cross-Sectional Studies; Mpox (monkeypox); Monkeypox virus; Public Health; Retrospective Studies
PubMed: 37657009
DOI: 10.1097/MD.0000000000034664 -
European Journal of Neurology Oct 2021An incremental number of cases of acute transverse myelitis (ATM) in individuals with ongoing or recent coronavirus disease 2019 (COVID-19) have been reported.
BACKGROUND AND PURPOSE
An incremental number of cases of acute transverse myelitis (ATM) in individuals with ongoing or recent coronavirus disease 2019 (COVID-19) have been reported.
METHODS
A systematic review was performed of cases of ATM described in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by screening both articles published and in preprint.
RESULTS
Twenty cases were identified. There was a slight male predominance (60.0%) and the median age was 56 years. Neurological symptoms first manifested after a mean of 10.3 days from the first onset of classical, mostly respiratory symptoms of COVID-19. Overall, COVID-19 severity was relatively mild. Polymerase chain reaction of cerebrospinal fluid for SARS-CoV-2 was negative in all 14 cases examined. Cerebrospinal fluid findings reflected an inflammatory process in most instances (77.8%). Aquaporin-4 and myelin oligodendrocyte protein antibodies in serum (tested in 10 and nine cases, respectively) were negative. On magnetic resonance imaging, the spinal cord lesions spanned a mean of 9.8 vertebral segments, necrotic-hemorrhagic transformation was present in three cases and two individuals had additional acute motor axonal neuropathy. More than half of the patients received a second immunotherapy regimen. Over a limited follow-up period of several weeks, 90% of individuals recovered either partially or near fully.
CONCLUSION
Although causality cannot readily be inferred, it is possible that cases of ATM occur para- or post-infectiously in COVID-19. All identified reports are anecdotal and case descriptions are heterogeneous. Whether the condition and the observed radiological characteristics are specific to SARS-CoV-2 infection needs to be clarified.
Topics: COVID-19; Guillain-Barre Syndrome; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myelitis, Transverse; SARS-CoV-2
PubMed: 34060708
DOI: 10.1111/ene.14952 -
Scientific Reports Feb 2024The COVID-19 pandemic has impacted individuals differently, and there's been a growing body of evidence pointing to neurological complications caused by the virus.... (Meta-Analysis)
Meta-Analysis
The COVID-19 pandemic has impacted individuals differently, and there's been a growing body of evidence pointing to neurological complications caused by the virus. However, our understanding of the range of neurological issues linked to SARS-CoV-2 infection in children is limited. This systematic review and meta-analysis aimed to assess the abnormal neuroimaging findings in pediatric COVID-19 patients, shedding light on this crucial aspect of the disease's impact on children. We conducted an extensive search in the PubMed, Medline, and ScienceDirect databases for observational studies reporting neuroimaging findings of the brain and spinal cord in children with COVID-19 between December 1, 2019, and October 30, 2021. Grey literature sources, including medRxiv and Google Scholar, were also explored. Pooled proportions of abnormal neuroimaging findings, categorized into neurovascular findings, ADEM-like lesions, encephalitic pattern, myelitis, transient splenial lesions, and other anomalies, were calculated using a random-effects model. Between-study heterogeneity was assessed using the χ statistic for pooled proportions and the inconsistency index I. The Quality of the studies was evaluated using the NIH Quality Assessment Tool and the adapted Newcastle-Ottawa Scale. Our search yielded 9,605 articles, with 96 studies (involving 327 pediatric patients) included in the qualitative analysis. Of these, five reports (encompassing 111 patients) underwent quantitative analysis. The pooled proportion of pediatric COVID-19 patients with neurological symptoms and exhibiting abnormal neuroimaging findings was 43.74%. These findings were further categorized into neurovascular findings (8.22%), ADEM-like lesions (7.69%), encephalitic pattern (13.95%), myelitis (4.60%), transient splenial lesions (16.26%), and other abnormalities (12.03%). Insignificant between-study heterogeneity was observed in all categories, and our analysis did not reveal significant publication bias. In conclusion, a substantial proportion of pediatric COVID-19 patients with neurological symptoms have abnormal neuroimaging findings, underscoring the need for vigilant monitoring of neurological complications in this vulnerable population. Standardized reporting and long-term follow-up studies are essential to fully understand the implications of these findings. Collaborative research efforts will deepen our understanding of COVID-19's neurological dimensions in children and enhance clinical care for this population.
Topics: Child; Humans; COVID-19; Encephalitis; Myelitis; Nervous System Diseases; Neuroimaging
PubMed: 38413808
DOI: 10.1038/s41598-024-55597-2