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Journal of Neuro-ophthalmology : the... Jul 2024Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic...
Optic Disc Cupping in Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, and Multiple Sclerosis and Its Relationship With Optical Coherence Tomography Parameters: A Multicenter Study.
BACKGROUND
Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning.
METHODS
This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC.
RESULTS
Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = -0.60 and R = -0.64, respectively), inversely moderate in patients with MOGAD (R = -0.34 and R = -0.40, respectively), and weak in patients with NMOSD (R = -0.03 and R = -0.17, respectively).
CONCLUSIONS
Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.
PubMed: 38946028
DOI: 10.1097/WNO.0000000000002204 -
Magnetic Resonance in Medical Sciences... 2024This special issue of Magnetic Resonance in Medical Sciences is dedicated to "Advanced Techniques for MR Neuroimaging," featuring nine review articles authored by...
This special issue of Magnetic Resonance in Medical Sciences is dedicated to "Advanced Techniques for MR Neuroimaging," featuring nine review articles authored by leading experts. The reviews cover advancements in reproducible research practices, diffusion tensor imaging along the perivascular space, myelin imaging using magnetic susceptibility source separation, spinal cord quantitative MRI analysis, tractometry of visual white matter pathways, deep learning-based image enhancement, arterial spin labeling, the potential of radiomics, and MRI-based quantification of brain oxygen metabolism. These articles provide a comprehensive update on cutting-edge technologies and their applications in clinical and research settings, highlighting their impact on improving diagnostic accuracy and understanding of neurological disorders.
Topics: Humans; Neuroimaging; Magnetic Resonance Imaging; Brain; Diffusion Tensor Imaging; Image Processing, Computer-Assisted; Nervous System Diseases; Deep Learning
PubMed: 38945942
DOI: 10.2463/mrms.e.2024-1000 -
Microbes and Infection Jun 2024The endogenous retrovirus type W (HERV-W) is a human-specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found...
The endogenous retrovirus type W (HERV-W) is a human-specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found that the HERV-W envelope (ENV) protein negatively affects oligodendrogenesis and controls microglial cell polarization towards a myelinated axon associated and damaging phenotype. Such first functional assessments were conducted ex vivo, given the human-specific origin of HERV-W. Recent experimental evidence gathered on a novel transgenic mouse model, mimicking activation and expression of the HERV-W ENV protein, revealed that all glial cell types are impacted and that cellular fates, differentiation, and functions were changed. In order to identify HERV-W-specific signatures in glial cells, the current study analyzed the transcriptome of ENV protein stimulated microglial- and astroglial cells and compared the transcriptomic signatures to lipopolysaccharide (LPS) stimulated cells, owing to the fact that both ligands can activate toll-like receptor-4 (TLR-4). Additionally, a comparison between published disease associated glial signatures and the transcriptome of HERV-W ENV stimulated glial cells was conducted. We, therefore, provide here for the first time a detailed molecular description of specific HERV-W ENV evoked effects on those glial cell populations that are involved in smoldering neuroinflammatory processes relevant for progression of neurodegenerative diseases.
PubMed: 38944109
DOI: 10.1016/j.micinf.2024.105382 -
Nigerian Journal of Clinical Practice Jun 2024Demyelinating disorders of the central nervous system (CNS) are rare disorders characterized by inflammation and the selective destruction of CNS myelin. The incidence...
BACKGROUND
Demyelinating disorders of the central nervous system (CNS) are rare disorders characterized by inflammation and the selective destruction of CNS myelin. The incidence of this disorder is increasing in developed countries. Nigerian studies on the pediatric population on the subject are very scarce.
AIMS
The aim of the study was to document the epidemiology, clinical profile, and impact of late presentation on the treatment outcome of demyelinating diseases of the CNS in pediatric patients.
METHODS
The retrospective review of patients aged 1-15 years admitted in a tertiary hospital from January 2018 to December 2022 with various symptoms suggestive of demyelinating CNS disorders. The diagnosis was clinically and radiologically confirmed. Information retrieved from the case notes included patients' demographics, clinical symptoms and signs, number of days with symptoms to presentation in the hospital, results of the magnetic resonance imaging (MRI), treatment, and treatment outcomes. Data were entered in Excel sheet and results were presented in tables and percentages.
RESULTS
The incidence of demyelinating disorders over the period was 0.013% (10 out of 769 patients admitted over the period). Acute demyelinating encephalomyelitis (ADEM) was the most common disorder seen in the study population (60%, n = 6), followed by transverse myelitis and two (20%) had optic neuritis (ON). Most of the patients with ADEM were in the 1-5-year age group. The female-to-male ratio was 2.3:1. Paraplegia, visual impairment, and ataxia were the most common clinical presentations in the study population. One of the patients met the criteria for the diagnosis of multiple sclerosis during follow-up. Human immunodeficiency virus (HIV) was identified as the cause of demyelination in one case. Most of the patients improved with steroids.
CONCLUSION
ADEM was the most common clinical phenotype seen in this study. Patients with ADEM and ON had a better prognosis than transverse myelitis. Late presentation was also identified as a poor prognostic factor. Follow-up of cases is very important to monitor disease progression to multiple sclerosis.
Topics: Humans; Nigeria; Child; Female; Male; Adolescent; Child, Preschool; Retrospective Studies; Infant; Demyelinating Diseases; Magnetic Resonance Imaging; Incidence; Treatment Outcome; Myelitis, Transverse; Optic Neuritis
PubMed: 38943292
DOI: 10.4103/njcp.njcp_155_23 -
Pediatric Research Jun 2024Preterm white matter injury (PWMI) is the most common cause of brain injury in premature neonates. PWMI involves a differentiation arrest of oligodendrocytes, the...
BACKGROUND
Preterm white matter injury (PWMI) is the most common cause of brain injury in premature neonates. PWMI involves a differentiation arrest of oligodendrocytes, the myelinating cells of the central nervous system. Clemastine was previously shown to induce oligodendrocyte differentiation and myelination in mouse models of PWMI at a dose of 10 mg/kg/day. The minimum effective dose (MED) of clemastine is unknown. Identification of the MED is essential for maximizing safety and efficacy in neonatal clinical trials. We hypothesized that the MED in neonatal mice is lower than 10 mg/kg/day.
METHODS
Mouse pups were exposed to normoxia or hypoxia (10% FiO2) from postnatal day 3 (P3) through P10. Vehicle or clemastine at one of four doses (0.5, 2, 7.5 or 10 mg/kg/day) was given to hypoxia-exposed pups. Myelination was assessed at age P14 and 10 weeks to determine the MED. Clemastine pharmacokinetics were evaluated at steady-state on day 8 of treatment.
RESULTS
Clemastine rescued hypoxia-induced hypomyelination with a MED of 7.5 mg/kg/day. Pharmacokinetic analysis of the MED revealed C 44.0 ng/mL, t 4.6 h, and AUC 280.1 ng*hr/mL.
CONCLUSIONS
Based on these results, myelination-promoting exposures should be achievable with oral doses of clemastine in neonates with PWMI.
IMPACT
Preterm white matter injury (PWMI) is the most common cause of brain injury and cerebral palsy in premature neonates. Clemastine, an FDA-approved antihistamine, was recently identified to strongly promote myelination in a mouse model of PWMI and is a possible treatment. The minimum effective dose in neonatal rodents is unknown and is critical for guiding dose selection and balancing efficacy with toxicity in future clinical trials. We identified the minimum effective dose of clemastine and the associated pharmacokinetics in a murine chronic hypoxia model of PWMI, paving the way for a future clinical trial in human neonates.
PubMed: 38942888
DOI: 10.1038/s41390-024-03326-w -
FEBS Open Bio Jun 2024Peripheral nerve injuries result in significant loss of motor and sensory function, and the slow rate of nerve regeneration can prolong recovery time. Thus, approaches...
Peripheral nerve injuries result in significant loss of motor and sensory function, and the slow rate of nerve regeneration can prolong recovery time. Thus, approaches that promote axonal regeneration are critical to improve the outcomes for patients with peripheral nerve injuries. In this study, we investigated the effects of Ficus carica L. (fig) and Vaccinium macrocarpon Ait. (cranberry), which are rich in phytochemicals with demonstrable and diverse medicinal properties, on nerve regeneration in a mouse model of sciatic nerve crush. Our investigation revealed that fig extract, but not cranberry extract, prevented the decline in muscle weight and nerve conduction velocity induced by nerve crush. The fig extract also mitigated motor function impairment, myelin thinning, and axon diameter reduction, indicating its potential to promote nerve regeneration. Furthermore, the fig extract enhanced macrophage infiltration into the nerve tissue, suggesting that it could ameliorate nerve injury by promoting tissue repair via increased macrophage infiltration. The study provides valuable insights into the potential of the fig extract as a novel agent promoting nerve regeneration. Further investigation into the mechanisms underlying the action of fig extracts is needed to translate these findings into clinical applications for patients with peripheral nerve injuries.
PubMed: 38942739
DOI: 10.1002/2211-5463.13859 -
Neuroimaging Clinics of North America Aug 2024Optic neuritis is a common feature in multiple sclerosis and in 2 other autoimmune demyelinating disorders such as aquaporin-4 IgG antibody-associated neuromyelitis... (Review)
Review
Optic neuritis is a common feature in multiple sclerosis and in 2 other autoimmune demyelinating disorders such as aquaporin-4 IgG antibody-associated neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease. Although serologic testing is critical for differentiating these different autoimmune-mediated disorders, MR imaging, which is the preferred imaging modality for assessing the optic nerve, can provide valuable information, suggesting a specific diagnosis and guiding the appropriate serologic testing.
Topics: Humans; Multiple Sclerosis; Optic Nerve; Magnetic Resonance Imaging; Optic Neuritis; Neuromyelitis Optica; Neuroimaging
PubMed: 38942524
DOI: 10.1016/j.nic.2024.03.005 -
Neuroimaging Clinics of North America Aug 2024Spinal cord MRI plays an important role in the diagnosis and prognosis of multiple sclerosis (MS) and related disorders. The ANATOMICAL, pathologic, imaging and... (Review)
Review
Spinal cord MRI plays an important role in the diagnosis and prognosis of multiple sclerosis (MS) and related disorders. The ANATOMICAL, pathologic, imaging and prognostic consideriations for the spinal cord for MS and the most important other demyelinating disorders, neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein-associated disease, are reviewed. Finally, differential diagnostic considerations of spinal cord MRI in MS and related disorders are discussed.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Spinal Cord; Neuromyelitis Optica; Diagnosis, Differential
PubMed: 38942523
DOI: 10.1016/j.nic.2024.03.011 -
Neuroimaging Clinics of North America Aug 2024In recent decades, advances in neuroimaging have profoundly transformed our comprehension of central nervous system demyelinating diseases. Remarkable technological... (Review)
Review
In recent decades, advances in neuroimaging have profoundly transformed our comprehension of central nervous system demyelinating diseases. Remarkable technological progress has enabled the integration of cutting-edge acquisition and postprocessing techniques, proving instrumental in characterizing subtle focal changes, diffuse microstructural alterations, and macroscopic pathologic processes. This review delves into state-of-the-art modalities applied to multiple sclerosis, neuromyelitis optica spectrum disorders, and myelin oligodendrocyte glycoprotein antibody-associated disease. Furthermore, it explores how this dynamic landscape holds significant promise for the development of effective and personalized clinical management strategies, encompassing support for differential diagnosis, prognosis, monitoring treatment response, and patient stratification.
Topics: Humans; Neuroimaging; Brain; Demyelinating Diseases; Neuromyelitis Optica; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 38942520
DOI: 10.1016/j.nic.2024.03.003 -
Neuroimaging Clinics of North America Aug 2024The diagnostic workup of multiple sclerosis (MS) has evolved considerably. The 2017 revision of the McDonald criteria shows high sensitivity and accuracy in predicting... (Review)
Review
The diagnostic workup of multiple sclerosis (MS) has evolved considerably. The 2017 revision of the McDonald criteria shows high sensitivity and accuracy in predicting clinically definite MS in patients with a typical clinically isolated syndrome and allows an earlier MS diagnosis. Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease (MOGAD) are recognized as separate conditions from MS, with specific diagnostic criteria. New MR imaging markers may improve diagnostic specificity for these conditions, thus reducing the risk of misdiagnosis. This study summarizes the most recent updates regarding the application of MR imaging for the diagnosis of MS, NMOSD, and MOGAD.
Topics: Humans; Neuromyelitis Optica; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Magnetic Resonance Imaging; Immunoglobulin G; Diagnosis, Differential
PubMed: 38942518
DOI: 10.1016/j.nic.2024.03.001