-
Genes Dec 2023Optic neuritis (ON) is an inflammatory condition affecting the optic nerve, leading to vision impairment and potential vision loss. This manuscript aims to provide a... (Review)
Review
Optic neuritis (ON) is an inflammatory condition affecting the optic nerve, leading to vision impairment and potential vision loss. This manuscript aims to provide a comprehensive review of the current understanding of ON, including its definition, epidemiology, physiology, genetics, molecular pathways, therapy, ongoing clinical studies, and future perspectives. ON is characterized by inflammation of the optic nerve, often resulting from an autoimmune response. Epidemiological studies have shown a higher incidence in females and an association with certain genetic factors. The physiology of ON involves an immune-mediated attack on the myelin sheath surrounding the optic nerve, leading to demyelination and subsequent impairment of nerve signal transmission. This inflammatory process involves various molecular pathways, including the activation of immune cells and the release of pro-inflammatory cytokines. Genetic factors play a significant role in the susceptibility to ON. Several genes involved in immune regulation and myelin maintenance have been implicated in the disease pathogenesis. Understanding the genetic basis can provide insights into disease mechanisms and potential therapeutic targets. Therapy for ON focuses on reducing inflammation and promoting nerve regeneration. Future perspectives involve personalized medicine approaches based on genetic profiling, regenerative therapies to repair damaged myelin, and the development of neuroprotective strategies. Advancements in understanding molecular pathways, genetics, and diagnostic tools offer new opportunities for targeted therapies and improved patient outcomes in the future.
Topics: Animals; Female; Humans; Encephalomyelitis, Autoimmune, Experimental; Optic Neuritis; Optic Nerve; Inflammation; Cytokines
PubMed: 38137014
DOI: 10.3390/genes14122192 -
Antioxidants (Basel, Switzerland) Jul 2023Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve.... (Review)
Review
Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.
PubMed: 37508003
DOI: 10.3390/antiox12071465 -
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 -
The Journal of Emergency Medicine Apr 2024Multiple sclerosis (MS) is a rare but serious condition associated with significant morbidity. (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a rare but serious condition associated with significant morbidity.
OBJECTIVE
This review provides a focused assessment of MS for emergency clinicians, including the presentation, evaluation, and emergency department (ED) management based on current evidence.
DISCUSSION
MS is an autoimmune disorder targeting the central nervous system (CNS), characterized by clinical relapses and radiological lesions disseminated in time and location. Patients with MS most commonly present with long tract signs (e.g., myelopathy, asymmetric spastic paraplegia, urinary dysfunction, Lhermitte's sign), optic neuritis, or brainstem syndromes (bilateral internuclear ophthalmoplegia). Cortical syndromes or multifocal presentations are less common. Radiologically isolated syndrome and clinically isolated syndrome (CIS) may or may not progress to chronic forms of MS, including relapsing remitting MS, primary progressive MS, and secondary progressive MS. The foundation of outpatient management involves disease-modifying therapy, which is typically initiated with the first signs of disease onset. Management of CIS and acute flares of MS in the ED includes corticosteroid therapy, ideally after diagnostic testing with imaging and lumbar puncture for cerebrospinal fluid analysis. Emergency clinicians should evaluate whether patients with MS are presenting with new-onset debilitating neurological symptoms to avoid unnecessary testing and admissions, but failure to appropriately diagnose CIS or MS flare is associated with increased morbidity.
CONCLUSIONS
An understanding of MS can assist emergency clinicians in better diagnosing and managing this neurologically devastating disease.
Topics: Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Radiography; Optic Neuritis; Magnetic Resonance Imaging
PubMed: 38472027
DOI: 10.1016/j.jemermed.2023.12.003 -
Skeletal Radiology Sep 2023Beginning in May 2022, monkeypox infection and vaccination rates dramatically increased due to a worldwide outbreak. This case highlights magnetic resonance (MR)...
Beginning in May 2022, monkeypox infection and vaccination rates dramatically increased due to a worldwide outbreak. This case highlights magnetic resonance (MR) neurography findings in an individual who developed Parsonage-Turner syndrome (PTS) 5 days after monkeypox symptom onset and 12 days after receiving the JYNNEOS vaccination. MR neurography of the patient's left suprascapular nerve demonstrated intrinsic hourglass-like constrictions, a characteristic finding of peripheral nerves involved in PTS. Other viral infections and vaccinations are well-documented triggers of PTS, an underrecognized peripheral neuropathy that is thought to be immune-mediated and results in severe upper extremity pain and weakness. The close temporal relationship between monkeypox infection and vaccination, and PTS onset, in this case, suggests a causal relationship and marks the first known report of peripheral neuropathy associated with monkeypox.
Topics: Humans; Brachial Plexus Neuritis; Mpox (monkeypox); Magnetic Resonance Imaging; Peripheral Nervous System Diseases; Vaccination
PubMed: 36752829
DOI: 10.1007/s00256-023-04298-4 -
Neurology(R) Neuroimmunology &... May 2024Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of visual pathway neuroprotection trials.
METHODS
This is a secondary analysis of longitudinal data from the TONE trial, which included 103 patients from 12 German academic tertiary centers with acute unilateral optic neuritis as a clinically isolated syndrome and baseline high-contrast visual acuity <0.5 decimal. Patients were randomized to 1,000 mg methylprednisolone i.v./d plus either erythropoietin (33,000 IU/d) or placebo (saline solution) for 3 days. They were followed up at standardized intervals with a battery of tests including high-contrast visual acuity, low-contrast letter acuity, contrast sensitivity, visual fields, visual evoked potentials, and retinal optical coherence tomography. At 6 months, participants answered a standardized questionnaire on vision-related quality of life (NEI-VFQ 25). We describe the disease course with mixed-effects piecewise linear models and calculate structure-function correlations using Pearson r. Because erythropoietin had no effect on the visual system, we use pooled (treatment-agnostic) data.
RESULTS
Patients experienced initial rapid and then decelerating improvements of visual function with thinning of inner and thickening of outer retinal layers. At 6 months, visual parameters were positively correlated with inner and negatively correlated with outer retinal thickness changes. Peripapillary retinal nerve fiber layer thinning predominantly occurred in sectors without previous swelling. At 6 months, macular ganglion cell and inner plexiform layer thinning was weakly correlated with the P100 peak time (r = -0.11) and moderately correlated with the amplitude of visual evoked potentials (r = 0.35). Only functional outcomes were at least moderately correlated with vision-related quality of life.
DISCUSSION
The longitudinal data from this large study cohort may serve as a reference for the clinical course of acute optic neuritis. The pattern of correlation between visual evoked potentials and inner retinal thinning may argue that the latter is mostly due to ganglion cell loss, rather than dysfunction. Visual pathway neuroprotection trials with functional outcomes are needed to confirm that candidate drugs will benefit patients' vision-related quality of life.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov, NCT01962571.
Topics: Humans; Young Adult; Disease Progression; Erythropoietin; Evoked Potentials, Visual; Optic Neuritis; Quality of Life
PubMed: 38588480
DOI: 10.1212/NXI.0000000000200223 -
Multiple Sclerosis and Related Disorders Aug 2023Previous cross-sectional studies have reported distinct clinical and radiological features among the different acute optic neuritis (ON) aetiologies. Nevertheless, these...
BACKGROUND
Previous cross-sectional studies have reported distinct clinical and radiological features among the different acute optic neuritis (ON) aetiologies. Nevertheless, these reports often included the same number of patients in each group, not taking into account the disparity in frequencies of ON aetiologies in a real-life setting and thus, it remains unclear what are the truly useful features for distinguishing the different ON causes. To determine whether clinical evaluation, ophthalmological assessment including the optical coherence tomography (OCT), CSF analysis, and MRI imaging may help to discriminate the different causes of acute ON in a real-life cohort.
METHODS
In this prospective monocentric study, adult patients with recent acute ON (<1 month) underwent evaluation at baseline and 1 and 12 months, including, high- and low-contrast visual acuity, visual field assessment and OCT measurements, baseline CSF analysis and MRI.
RESULTS
Among 108 patients, 71 (65.7%) had multiple sclerosis (MS), 19 (17.6%) had idiopathic ON, 13 (12.0%) and 5 (4.6%) had myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, at last follow up respectively.At baseline, the distribution of bilateral ON, CSF-restricted oligoclonal bands, optic perineuritis, optic nerve length lesions and positive dissemination in space and dissemination in time criteria on MRI were significantly different between the four groups (p <0.001). No significant difference in visual acuity nor inner retinal layer thickness was found between the different ON aetiologies.
CONCLUSIONS
In this large prospective study, bilateral visual involvement, CSF and MRI results are the most useful clues in distinguishing the different aetiologies of acute ON, whereas ophthalmological assessments including OCT measurements revealed no significant difference between the aetiologies.
Topics: Humans; Prospective Studies; Optic Neuritis; Optic Nerve; Myelin-Oligodendrocyte Glycoprotein; Multiple Sclerosis; Tomography, Optical Coherence; Vision Disorders
PubMed: 37270881
DOI: 10.1016/j.msard.2023.104764 -
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 -
Frontiers in Neurology 2023This study proposes a "modular management" approach for vestibular neuritis (VN) to reduce chronicization and improve patient prognosis. The approach involves...
OBJECTIVE
This study proposes a "modular management" approach for vestibular neuritis (VN) to reduce chronicization and improve patient prognosis. The approach involves multi-factor grading and hierarchical intervention and was found to be more effective than traditional treatment strategies.
METHODS
This retrospective analysis compared two groups of VN patients from two medical institutions. The intervention group of 52 patients received "modular management," while the control group of 51 patients did not receive this kind of management. Analyzed the early treatment strategies, 6-month prognosis, and other indicators of the two groups of patients, compared and analyzed their overall prognosis, and identified the risk factors affecting the chronicization.
RESULTS
The modular management group had lower dizziness severity, better balance, lower anxiety, and higher video head impulse testing (v-HIT) gain after 6 months of onset. Analysis of factors related to persistent postural-perceptual dizziness (PPPD) in patients with VN showed positive correlations between the time from onset to diagnosis and PPPD, and Vertigo Symptom Scale (VSS), Dizziness Handicap Inventory (DHI), anxiety, and depression. Normalized vestibular rehabilitation was negatively correlated with PPPD, while gender, age, and early steroid use had no significant correlation. The multi-factor logistic regression model correctly classified 93.20% of the study subjects with a sensitivity of 87.50% and specificity of 94.90%.
CONCLUSION
The proposed "modular management" scheme for VN is a comprehensive and dynamic approach that includes health education, assessment, rehabilitation, therapy, evaluation, and prevention. It can significantly improve patient prognosis and reduce chronicization by shifting from simple acute treatment to continuous management.
PubMed: 37780705
DOI: 10.3389/fneur.2023.1243034 -
Multiple Sclerosis and Related Disorders Sep 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS demyelinating disease that targets myelin oligodendrocyte glycoprotein and recurs in...
BACKGROUND
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS demyelinating disease that targets myelin oligodendrocyte glycoprotein and recurs in approximately 50% of patients after the initial episode. Multiple relapses may have adverse consequences, but the factors influencing relapse are unclear. This study analyzed the clinical risk factors for relapse in patients with MOGAD.
METHODS
Twenty-four MOGAD patients diagnosed at the Department of Neurology, First Hospital of Shanxi Medical University from March 2018 to November 2020 were retrospectively analyzed in this study. The patients were divided into a monophasic course and a relapsing course according to their disease process. The patients' epidemiological characteristics, clinical symptoms, laboratory tests, imaging features, and regression were summarized. Comparisons were made between the monophasic and relapsing course to identify the possible factors associated with the clinical features and recurrence.
RESULTS
At a mean follow-up of 15 months (range: 8 to 24 months), seventeen of the 24 patients (70.8%) had monophasic disease, and 7 (29.2%) had relapsing disease. Among the 24 patients, 17 patients (70.9%) had low Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) serum titers (<1:100), and 7 patients (29.1%) had high MOG-IgG serum titers (≥1:100). Compared to the monophasic course group, patients in the relapsing course group had higher serum antibody titers (71.4% vs. 11.7%, P = 0.035). Onset phenotypes included encephalitis (50%), myelitis (45.8%), and optic neuritis (45.8%), with 66.7% of patients starting with a single phenotype and 33.3% starting with two or more phenotypes. Optic neuritis was more common in the relapsing course group (85.7%) than the monophasic course group (29.4%) (P = 0.023). There was no significant difference between the two groups in the proportion of myelitis and encephalitis. A previous history or background of immunological disease was present in 33.3% of patients, with a significantly higher proportion in the relapsing course group than in the monophasic course group (71.4% vs. 17.6%, P = 0.021). Regarding ancillary examinations, the relapsing course group was more likely to have CSF leukocytes higher than 50/mm than the monophasic course group (60% vs. 0, P = 0.045), while there was no difference in the number and site distribution of the lesions on MRI.
CONCLUSIONS
Our study suggests that the most common clinical manifestations of MOGAD are diminished visual acuity, limb/facial numbness, and ocular/orbital pain. The onset phenotype consisting of optic neuritis, a history of immune disease, high antibody titers (≥1:100), and high cerebrospinal fluid leukocytes (above 50/mm) suggests a high likelihood of MOGAD recurrence.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Retrospective Studies; Optic Neuritis; Myelitis; Encephalitis; Chronic Disease; Immunoglobulin G; Recurrence; Autoantibodies
PubMed: 37442076
DOI: 10.1016/j.msard.2023.104879