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Nature Reviews. Drug Discovery Aug 2023
Topics: Humans; Poliomyelitis; Global Health
PubMed: 37400708
DOI: 10.1038/d41573-023-00107-8 -
La Revue Du Praticien Mar 2024VACCINATION OF SENIORS. In France, the vaccination schedule for seniors (people aged 65 and over) recommends 4 vaccinations (Covid-19, flu, DTP [diphtheria, tetanus,...
VACCINATION OF SENIORS. In France, the vaccination schedule for seniors (people aged 65 and over) recommends 4 vaccinations (Covid-19, flu, DTP [diphtheria, tetanus, poliomyelitis] and shingles), plus 3 others in the event of a particular risk (pneumococcus, whooping cough, hepatitis A). Nevertheless, vaccination coverage for these infectious diseases remains insufficient, making an increasingly heavy medical and economic burden in an aging population. Vaccination of seniors must become a priority public health objective and involve all health professionals, first and foremost treating physicians. It must be improved by integrating advances in vaccinology and digital technologies into a program aimed at maintaining vaccination coverage throughout life.
Topics: Humans; Aged; Vaccination; Tetanus; Diphtheria; Poliomyelitis; France
PubMed: 38551858
DOI: No ID Found -
MBio Aug 2023Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in...
Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in children. AFM outbreaks have been associated with increased circulation and genetic diversity of EV-D68 since 2014, although the virus was discovered in the 1960s. The mechanisms by which EV-D68 targets the central nervous system are unknown. Since enteroviruses are human pathogens that do not routinely infect other animal species, establishment of a human model of the central nervous system is essential for understanding pathogenesis. Here, we describe two human spinal cord organoid (hSCO)-based models for EV-D68 infection derived from induced, pluripotent stem cell (iPSC) lines. One hSCO model consists primarily of spinal motor neurons, while the another model comprises multiple neuronal cell lineages, including motor neurons, interneurons, and glial cells. These hSCOs can be productively infected with contemporary strains, but not a historic strain, of EV-D68 and produce extracellular virus for at least 2 weeks without appreciable cytopathic effect. By comparison, infection with hSCO with another enterovirus, echovirus 11, causes significant structural destruction and apoptosis. Together, these findings suggest that EV-D68 infection is not the sole mediator of neuronal cell death in the spinal cord in those with AFM and that secondary injury from the immune response likely contributes to pathogenesis. IMPORTANCE AFM is a rare condition that causes significant morbidity in affected children, often contributing to life-long sequelae. It is unknown how EV-D68 causes paralysis in children, and effective therapeutic and preventative strategies are not available. Mice are not native hosts for EV-D68, and thus, existing mouse models use immunosuppressed or neonatal mice, mouse-adapted viruses, or intracranial inoculations. To complement existing models, we report two hSCO models for EV-D68 infection. These three-dimensional, multicellular models comprised human cells and include multiple neural lineages, including motor neurons, interneurons, and glial cells. These new hSCO models for EV-D68 infection will contribute to understanding how EV-D68 damages the human spinal cord, which could lead to new therapeutic and prophylactic strategies for this virus.
Topics: Child; Humans; Animals; Mice; Enterovirus D, Human; Spinal Cord; Paralysis; Motor Neurons; Enterovirus Infections
PubMed: 37535397
DOI: 10.1128/mbio.01058-23 -
Journal of Neurology, Neurosurgery, and... Sep 2023Neuromyelitis optica spectrum disorders (NMOSDs) are a group of diseases mainly characterised by recurrent optic neuritis and/or myelitis. Most cases are associated with...
BACKGROUND AND OBJECTIVES
Neuromyelitis optica spectrum disorders (NMOSDs) are a group of diseases mainly characterised by recurrent optic neuritis and/or myelitis. Most cases are associated with a pathogenic antibody against aquaporin-4 (AQP4-Ab), while some patients display autoantibodies targeting the myelin oligodendrocyte glycoprotein (myelin oligodendrocyte glycoprotein antibodies (MOG-Abs)). Anti-Argonaute antibodies (Ago-Abs) were first described in patients with rheumatological conditions and were recently reported as a potential biomarker in patients with neurological disorders. The aims of the study were to investigate if Ago-Abs can be detected in NMOSD and to evaluate its clinical usefulness.
METHODS
Sera from patients prospectively referred to our centre with suspected NMOSD were tested for AQP4-Abs, MOG-Abs and Ago-Abs with cell-based assays.
RESULTS
The cohort included 104 prospective patients: 43 AQP4-Abs-positive cases, 34 MOG-Abs positive cases and 27 double-negative patients. Ago-Abs were detected in 7 of 104 patients (6.7%). Clinical data were available for six of seven patients. The median age at onset of patients with Ago-Abs was 37.5 [IQR 28.8-50.8]; five of six patients tested positive also for AQP4-Abs. Clinical presentation at onset was transverse myelitis in five patients, while one presented with diencephalic syndrome and experienced a transverse myelitis during follow-up. One case presented a concomitant polyradiculopathy. Median EDSS score at onset was 7.5 [IQR 4.8-8.4]; median follow-up was 40.3 months [IQR 8.3-64.7], and median EDSS score at last evaluation was 4.25 [IQR 1.9-5.5].
CONCLUSION
Ago-Abs are present in a subset of patients with NMOSD and, in some cases, represent the only biomarker of an autoimmune process. Their presence is associated with a myelitis phenotype and a severe disease course.
Topics: Humans; Myelitis, Transverse; Myelin-Oligodendrocyte Glycoprotein; Prospective Studies; Neuromyelitis Optica; Aquaporin 4; Biomarkers; Autoantibodies
PubMed: 36810322
DOI: 10.1136/jnnp-2022-330707 -
Multiple Sclerosis and Related Disorders Nov 2023Serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect the disease activity and disability in central nervous system (CNS)...
BACKGROUND
Serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect the disease activity and disability in central nervous system (CNS) demyelinating diseases. However, the clinical significance of NfL and GFAP in idiopathic transverse myelitis (iTM), an inflammatory spinal cord disease with unknown underlying causes, remains unclear. This study aimed to investigate NfL and GFAP levels in iTM and their association with the clinical parameters compared with those in TM with disease-specific antibodies such as anti-aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies (sTM).
METHODS
We collected serum and clinical data of 365 patients with CNS inflammatory diseases from 12 hospitals. The serum NfL and GFAP levels were measured in patients with iTM (n = 37) and sTM (n = 39) using ultrasensitive single-molecule array assays. Regression analysis was performed to investigate the associations between serum levels of NfL and GFAP and the clinical parameters such as higher EDSS scores (EDSS ≥ 4.0).
RESULTS
Mean NfL levels were not significantly different between iTM (50.29 pg/ml) and sTM (63.18 pg/ml) (p = 0.824). GFAP levels were significantly lower in iTM (112.34 pg/ml) than in sTM (3814.20 pg/ml) (p = 0.006). NfL levels correlated with expanded disability status scale (EDSS) scores in sTM (p = 0.001) but not in iTM (p = 0.824). Disease duration also correlated with higher EDSS scores in sTM (p = 0.017).
CONCLUSION
NfL levels and disease duration correlated with EDSS scores in sTM, and GFAP levels could be a promising biomarker to differentiate iTM from sTM.
Topics: Humans; Myelitis, Transverse; Multiple Sclerosis; Glial Fibrillary Acidic Protein; Intermediate Filaments; Aquaporin 4
PubMed: 37688927
DOI: 10.1016/j.msard.2023.104957 -
Molecular Therapy : the Journal of the... Sep 2023Neuromyelitis optica (NMO) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by transverse myelitis and optic neuritis. The...
Neuromyelitis optica (NMO) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by transverse myelitis and optic neuritis. The pathogenic serum IgG antibody against the aquaporin-4 (AQP4) on astrocytes triggers the activation of the complement cascade, causing astrocyte injury, followed by oligodendrocyte injury, demyelination, and neuronal loss. Complement C3 is positioned as a central player that relays upstream initiation signals to activate downstream effectors, potentially stimulating and amplifying host immune and inflammatory responses. However, whether targeting the inhibition of C3 signaling could ameliorate tissue injury, locomotor defects, and visual impairments in NMO remains to be investigated. In this study, using the targeted C3 inhibitor CR2-Crry led to a significant decrease in complement deposition and demyelination in both slice cultures and focal intracerebral injection models. Moreover, the treatment downregulated the expression of inflammatory cytokines and improved motor dysfunction in a systemic NMO mouse model. Similarly, employing serotype 2/9 adeno-associated virus (AAV2/9) to induce permanent expression of CR2-Crry resulted in a reduction in visual dysfunction by attenuating NMO-like lesions. Our findings reveal the therapeutic value of inhibiting the complement C3 signaling pathway in NMO.
Topics: Animals; Mice; Complement C3; Neuromyelitis Optica; Aquaporin 4; Vision Disorders; Astrocytes; Signal Transduction; Recombinant Fusion Proteins
PubMed: 37481702
DOI: 10.1016/j.ymthe.2023.07.017 -
Journal of the Neurological Sciences Jul 2023To assess marked central canal T2-hyperintensity in patients with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) myelitis compared to myelitis...
OBJECTIVE
To assess marked central canal T2-hyperintensity in patients with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) myelitis compared to myelitis patients with aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and multiple sclerosis (MS).
MATERIAL/METHODS
Two blinded raters evaluated spinal cord magnetic resonance imaging (MRIs) of myelitis patients with MOGAD (n = 63), AQP4 + NMOSD (n = 37), and MS (n = 26), assessing for marked central canal T2-hyperintensity and its evolution. If there were conflicting results, a third neurologist assessed the MRI.
RESULTS
Marked central canal T2-hyperintensity was more frequent in patients with MOGAD (18/63[29%]) than MS (1/26[4%]; p = 0.01) myelitis but did not differ from AQP4 + NMOSD (13/37[35%]; p = 0.49). Marked central canal T2-hyperintensity had completely resolved on follow-up axial MRI for most MOGAD (12/14[86%]) and AQP4 + NMOSD (10/10[100%]; p = 0.49) patients.
CONCLUSIONS
Marked central canal T2-hyperintensity is a common transient radiologic accompaniment of MOGAD and AQP4 + NMOSD myelitis, but not MS myelitis.
Topics: Myelin-Oligodendrocyte Glycoprotein; Myelitis, Transverse; Magnetic Resonance Imaging; Autoantibodies; Multiple Sclerosis; Diagnosis, Differential; Humans; Male; Female; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Spinal Canal; Spinal Cord
PubMed: 37201267
DOI: 10.1016/j.jns.2023.120687 -
Multiple Sclerosis (Houndmills,... Aug 2023The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown. (Observational Study)
Observational Study
BACKGROUND
The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown.
OBJECTIVE
The objective was to describe the outcomes of IVIG treatment for acute MOGAD attacks.
METHODS
A retrospective observational study involving seven tertiary neuroimmunology centers. Data collection included patients' demographics, Expanded Disability Status Scale (EDSS), and visual acuity (VA) before the attack, at the nadir of the attack before IVIG treatment, and at follow-up visits ⩾3 months after treatment.
RESULTS
Thirty-nine patients were included, of which 21 (53.8%) were female. The median age was 23 years (range 5-74 years), and the median disease duration was 4 months (range 0-93 months). The most common type of attack treated with IVIG was isolated optic neuritis (ON) (unilateral = 14, bilateral = 5, associated with transverse myelitis (TM), = 1), followed by acute disseminated encephalomyelitis (ADEM) ( = 8), multifocal ( = 7), TM ( = 3), brainstem ( = 1), and other encephalitis ( = 1). A significant improvement in both the EDSS and VA measures was observed at follow-up compared to the time of IVIG treatment initiation ( < 0.0001 for both outcome measures).
CONCLUSION
IVIG may be an effective treatment option for acute MOGAD attacks. Further prospective studies are warranted to validate our results.
Topics: Female; Male; Humans; Immunoglobulins, Intravenous; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Myelitis, Transverse; Encephalomyelitis, Acute Disseminated; Retrospective Studies; Neuromyelitis Optica
PubMed: 37431144
DOI: 10.1177/13524585231184738 -
Current Allergy and Asthma Reports Nov 2023Neuromyelitis optica (NMO) is an auto-immune disease essentially depicted by optic neuritis and transverse myelitis. Per se, NMO was initially believed to be a sub-type... (Review)
Review
PURPOSE OF REVIEW
Neuromyelitis optica (NMO) is an auto-immune disease essentially depicted by optic neuritis and transverse myelitis. Per se, NMO was initially believed to be a sub-type of multiple sclerosis with typical demyelinating cerebral lesions and optic nerve inflammation. More recently, corroborating lignes of evidence have strengthened the concept of the spectrum of diseases associated with NMO and more specifically with the role of anti-aquaporin-4 antibodies in the pathogenesis of disease.
RECENT FINDINGS
In this article, we review the recent pathogenic findings in NMO and more interestingly the newly discovered role of anti-aquaporin-4 antibodies as key players in triggering cerebral lesions. The concept of spectrum of diseases associated with NMO is also discussed. These recent findings have paved in the further understanding of the pathogenesis underlying NMO and new treatments are currently being developed targeting anti-aquaporin-4 antibodies.
Topics: Humans; Neuromyelitis Optica; Aquaporin 4; Autoimmune Diseases; Multiple Sclerosis; Autoantibodies
PubMed: 37889429
DOI: 10.1007/s11882-023-01112-y -
Continuum (Minneapolis, Minn.) Feb 2024This article describes an integrative strategy to evaluate patients with suspected myelopathy, provides advice on diagnostic approach, and outlines the framework for the...
OBJECTIVE
This article describes an integrative strategy to evaluate patients with suspected myelopathy, provides advice on diagnostic approach, and outlines the framework for the etiologic diagnosis of myelopathies.
LATEST DEVELOPMENTS
Advances in diagnostic neuroimaging techniques of the spinal cord and improved understanding of the immune pathogenic mechanisms associated with spinal cord disorders have expanded the knowledge of inflammatory and noninflammatory myelopathies. The discovery of biomarkers of disease, such as anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies involved in myelitis and other immune-related mechanisms, the emergence and identification of infectious disorders that target the spinal cord, and better recognition of myelopathies associated with vascular pathologies have expanded our knowledge about the broad clinical spectrum of myelopathies.
ESSENTIAL POINTS
Myelopathies include a group of inflammatory and noninflammatory disorders of the spinal cord that exhibit a wide variety of motor, sensory, gait, and sensory disturbances and produce major neurologic disability. Both inflammatory and noninflammatory myelopathies comprise a broad spectrum of pathophysiologic mechanisms and etiologic factors that lead to specific clinical features and presentations. Knowledge of the clinical variety of myelopathies and understanding of strategies for the precise diagnosis, identification of etiologic factors, and implementation of therapies can help improve outcomes.
Topics: Humans; Spinal Cord Diseases; Spinal Cord; Myelitis; Neuroimaging; Aquaporin 4
PubMed: 38330471
DOI: 10.1212/CON.0000000000001390