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European Journal of Neurology Jul 2024This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
Beyond T cell toxicity - Intrathecal chemokine CXCL13 indicating B cell involvement in immune-related adverse events following checkpoint inhibition: A two-case series and literature review.
BACKGROUND AND PURPOSE
This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
METHODS
A systematic literature review was made, with case observations of a melanoma and a non-small cell lung cancer (NSCLC) patient who developed ICI-associated nirAE with cerebrospinal fluid (CSF) findings indicating B cell involvement.
RESULTS
Two patients receiving ipilimumab/nivolumab for melanoma and chemotherapy/pembrolizumab for NSCLC developed nirAE in the form of myocarditis/myositis/myasthenia gravis overlap syndrome (triple M) and cerebellitis plus longitudinal transverse myelitis (c-LETM), respectively. Intrathecal inflammation with chemokine C-X-C motif ligand (CXCL13) elevation was present in both patients; the triple M case had acetylcholine receptor antibodies, antititin reactivity, altered CD4/CD8 T cell ratio in blood, and depressed programmed death-1 (PD-1) expression on CSF T cells; the c-LETM case showed intrathecal antibody production and plasma cells. Both patients insufficiently responded to first-line treatment. The NSCLC case improved upon administration of B cell-depleting therapy with rituximab, whereas the melanoma patient died before escalation therapy was initiated. Literature research revealed one additional ICI-associated LETM case with intrathecal CXCL13 elevation, three cases with ICI-associated aquaporin-4 antibody neuromyelitis spectrum disorder, and evidence of B cell-mediated toxicity based on antibody-mediated immune pathologies in ICI-associated immune-related adverse events.
CONCLUSIONS
The case observations highlight the plethora of uncertainties in diagnosis and treatment of ICI-associated nirAE, exemplify the heterogeneity of immune mechanisms involved, and suggest a role of B cells, which may be underdiagnosed. Intrathecal CXCL13 may serve as a biomarker of B cell involvement in nirAE, supported by intrathecal immunoglobulin synthesis, presence of plasma cells, and/or recruitment of cognate immune cells.
Topics: Aged; Female; Humans; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Chemokine CXCL13; Immune Checkpoint Inhibitors; Ipilimumab; Lung Neoplasms; Melanoma; Myelitis, Transverse; Nivolumab; T-Lymphocytes
PubMed: 38556899
DOI: 10.1111/ene.16279 -
Expert Review of Anti-infective Therapy May 2024Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP)....
INTRODUCTION
Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The evidence is limited regarding other diseases potentially associated with HTLV-1, such as HTLV-1-associated autoimmune diseases.
AREA COVERED
We summarized the available information on complications associated with HTLV-1 infection.
EXPERT OPINION
Previous studies showed that HTLV-1 carriers have an increased incidence of collagen diseases including Sjögren's syndrome, as well as dysthyroidism, diabetes mellitus, and atherosclerosis. Furthermore, cognitive deficits are observed in asymptomatic carriers and in symptomatic carriers who develop HAM/TSP. It is hypothesized that altered immunoregulation occurs as a result of persistent HTLV-1 infection. A systematic review and meta-analysis demonstrated that HTLV-1 infection itself has an adverse impact on overall survival. ATL alone cannot entirely explain the adverse impact of HTLV-1 infection on overall mortality, because the incidence is low, and therefore HTLV-1-associated diseases as a whole may contribute to the inferior clinical outcome. However, there are insufficient data to determine the causal relationship between HTLV-1 infection and each complication. While non-cancerous events linked to HTLV-1 infection are not fatal, they are likely to reduce quality of life. Large prospective studies should be conducted by international collaborators.
Topics: Humans; Autoimmune Diseases; Carrier State; HTLV-I Infections; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic
PubMed: 38536666
DOI: 10.1080/14787210.2024.2336547 -
European Journal of Neurology Jul 2024This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A), a rare but severe neuroinflammatory disorder, to facilitate early diagnosis and appropriate treatment.
METHODS
A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis)-conforming systematic review and meta-analysis was performed on all available data from January 2016 to June 2023. Clinical and neuroimaging phenotypes were extracted for both adult and paediatric forms.
RESULTS
A total of 93 studies with 681 cases (55% males; median age = 46, range = 1-103 years) were included. Of these, 13 studies with a total of 535 cases were eligible for the meta-analysis. Clinically, GFAP-A was often preceded by a viral prodromal state (45% of cases) and manifested as meningitis, encephalitis, and/or myelitis. The most common symptoms were headache, fever, and movement disturbances. Coexisting autoantibodies (45%) and neoplasms (18%) were relatively frequent. Corticosteroid treatment resulted in partial/complete remission in a majority of cases (83%). Neuroimaging often revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities (74%) as well as perivascular (45%) and/or leptomeningeal (30%) enhancement. Spinal cord abnormalities were also frequent (49%), most commonly manifesting as longitudinally extensive myelitis. There were 88 paediatric cases; they had less prominent neuroimaging findings with lower frequencies of both T2/FLAIR hyperintensities (38%) and contrast enhancement (19%).
CONCLUSIONS
This systematic review and meta-analysis provide high-level evidence for clinical and imaging phenotypes of GFAP-A, which will benefit the identification and clinical workup of suspected cases. Differential diagnostic cues to distinguish GFAP-A from common clinical and imaging mimics are provided as well as suitable magnetic resonance imaging protocol recommendations.
Topics: Humans; Astrocytes; Autoantibodies; Autoimmune Diseases of the Nervous System; Glial Fibrillary Acidic Protein; Neuroimaging; Neuroinflammatory Diseases; Phenotype
PubMed: 38506182
DOI: 10.1111/ene.16284 -
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 -
Frontiers in Public Health 2024Human T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Human T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and HTLV-1-Associated Myelopathy (HAM). Found in endemic clusters across the world, high prevalence has been reported in minoritized groups who suffer from health inequities. This study investigates the association between HTLV-1 prevalence and the following socioeconomic determinants of health: education, income, and employment, which are markers of health inequity.
METHODS
A systematic review was conducted by searching the following databases: Ovid/Medline, Embase, Global Health Database, Web of Science, LILACS and SciELO. Primary studies in English, Spanish and Portuguese mentioning HTLV-1 and one of education, income and/or employment were included. A random-effects meta-analysis was performed, and odds ratios (OR) were calculated to determine the association between these socioeconomic determinants of health and HTLV-1 prevalence.
RESULTS
42 studies were included. The likelihood of having HTLV-1 was higher in individuals with less than completed primary education compared to those who completed primary education (OR 1.86 [95% CI 1.34-2.57]; < 0.01). This may be because individuals with low education have reduced access to and understanding of health information, thus increasing the prevalence of risk factors associated with HTLV-1 infection. No other determinants were found to be statistically significant.
CONCLUSION
Fewer years of schooling are associated with increased likelihood of contracting HTLV-1. Therefore, health promotion materials and public health policies regarding HTLV-1 must consider those with lower educational levels to effectively reduce disease transmission.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335004, identifier (CRD42022335004).
Topics: Humans; Adult; Human T-lymphotropic virus 1; HTLV-I Infections; Paraparesis, Tropical Spastic; Risk Factors; Socioeconomic Factors
PubMed: 38327581
DOI: 10.3389/fpubh.2024.1298308 -
International Journal of Radiation... Jun 2024Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT... (Review)
Review
PURPOSE
Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex.
METHODS AND MATERIALS
We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity.
RESULTS
Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events.
CONCLUSIONS
This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.
Topics: Humans; Child; Adolescent; Child, Preschool; Male; Infant; Radiation Injuries; Female; Neoplasms; Radiotherapy Dosage; Myelitis; Medulloblastoma; Risk Factors; Rhabdomyosarcoma; Hodgkin Disease; Age Factors; Spinal Cord Diseases
PubMed: 38323945
DOI: 10.1016/j.ijrobp.2023.12.020 -
Current Drug Safety Jan 2024The objective of this study was to conduct a systematic review of research pertaining to the COVID-19 vaccine and its association with neurological complications.
AIMS & OBJECTIVES
The objective of this study was to conduct a systematic review of research pertaining to the COVID-19 vaccine and its association with neurological complications.
METHOD
We performed a comprehensive search of the literature using Google Scholar, PubMed, and NCBI databases from December 2021 to December 2022. For Google Scholar, PubMed, and NCBI databases we used the following key search terms: "neurological adverse effects", "COVID-19 vaccination", "SARS-CoV-2", CNS complications, and CNS adverse effects. Two reviewer authors individually searched and assessed the titles and abstracts of all articles. The third reviewer resolved the disagreement between them. Data were documented regarding title, study location, type of study, type of COVID-19 vaccine, type of neurological complications/adverse effects, and sample size.
RESULTS
From our findings, it is confirmed that these neurological complications like GuillainBarre syndrome (23.6%), Neuromyelitis Optica spectrum disorder (5.5%), Neuropathy (6.9%), Transverse Myelitis (8.3%) and Acute disseminated Encephalomyelitis (4.1%) are majorly affected in most of the people. The increase in risks associated with SARS-CoV-2 infection far outweighs any previously reported associations with vaccination.
CONCLUSION
We found no safety signal was observed between COVID-19 vaccines and the immune-mediated neurological events. Before assuming a causal relationship, the side effects of the COVID-19 vaccine should first be carefully examined to rule out known associated factors. Symptom onset was within two weeks of vaccination in the majority of cases; as such, this seems to be a high-risk period warranting vigilance.
PubMed: 38275049
DOI: 10.2174/0115748863273931231121072231 -
Vaccine Feb 2024Delays in achieving polio eradication have led to ongoing risks of poliovirus importations that may cause outbreaks in polio-free countries. Because of the low, but...
Trade-offs of different poliovirus vaccine options for outbreak response in the United States and other countries that only use inactivated poliovirus vaccine (IPV) in routine immunization.
Delays in achieving polio eradication have led to ongoing risks of poliovirus importations that may cause outbreaks in polio-free countries. Because of the low, but non-zero risk of paralysis with oral poliovirus vaccines (OPVs), countries that achieve and maintain high national routine immunization coverage have increasingly shifted to exclusive use of inactivated poliovirus vaccine (IPV) for all preventive immunizations. However, immunization coverage within countries varies, with under-vaccinated subpopulations potentially able to sustain transmission of imported polioviruses and experience local outbreaks. Due to its cost, ease-of-use, and ability to induce mucosal immunity, using OPV as an outbreak control measure offers a more cost-effective option in countries in which OPV remains in use. However, recent polio outbreaks in IPV-only countries raise questions about whether and when IPV use for outbreak response may fail to stop poliovirus transmission and what consequences may follow from using OPV for outbreak response in these countries. We systematically reviewed the literature to identify modeling studies that explored the use of IPV for outbreak response in IPV-only countries. In addition, applying a model of the 2022 type 2 poliovirus outbreak in New York, we characterized the implications of using different OPV formulations for outbreak response instead of IPV. We also explored the hypothetical scenario of the same outbreak except for type 1 poliovirus instead of type 2. We find that using IPV for outbreak response will likely only stop outbreaks for polioviruses of relatively low transmission potential in countries with very high overall immunization coverage, seasonal transmission dynamics, and only if IPV immunization interventions reach some unvaccinated individuals. Using OPV for outbreak response in IPV-only countries poses substantial risks and challenges that require careful consideration, but may represent an option to consider for some outbreaks in some populations depending on the properties of the available vaccines and coverage attainable.
Topics: Humans; United States; Poliovirus Vaccine, Inactivated; Poliovirus; Poliovirus Vaccine, Oral; Poliomyelitis; Disease Outbreaks; Vaccination; New York
PubMed: 38218668
DOI: 10.1016/j.vaccine.2023.12.081 -
Transactions of the Royal Society of... Mar 2024This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series.
BACKGROUND
This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist.
RESULTS
A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients.
CONCLUSIONS
This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.
Topics: Humans; Brain; Central Nervous System; Cohort Studies; Leprosy; Mycobacterium leprae; Case Reports as Topic; Central Nervous System Diseases
PubMed: 37850518
DOI: 10.1093/trstmh/trad072 -
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