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Muscle & Nerve Nov 2023Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves... (Review)
Review
Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves as an antigen for immunoglobulin M (IgM) monoclonal antibodies. Individuals who harbor anti-MAG antibodies classically develop a progressive autoimmune peripheral neuropathy characterized clinically by ataxia, distal sensory loss, and gait instability, and electrophysiologically by distally accentuated conduction velocity slowing. Although off-label immunotherapy is common, there are currently no proven effective disease-modifying therapeutics, and most patients experience slow accumulation of disability over years and decades. The typically slowly progressive nature of this neuropathy presents unique challenges when trying to find effective anti-MAG therapeutic agents. Drug development has also been hampered by the lack of validated outcome measures that can detect clinically meaningful changes in a reasonable amount of time as well as by the lack of disease activity biomarkers. In this invited review, we provide an update on the state of clinicometric outcome measures and disease activity biomarkers in anti-MAG neuropathy. We highlight the insensitivity of widely used existing clinicometric outcome measures such as the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score as well as the INCAT sensory subscore in anti-MAG neuropathy, referencing the two previous negative randomized controlled clinical trials evaluating rituximab. We then discuss newly emerging candidate therapeutic agents, including tyrosine kinase inhibitors and enhanced B-cell-depleting agents, among others. We conclude with a practical approach to the evaluation and management of anti-MAG neuropathy patients.
Topics: Humans; Myelin-Associated Glycoprotein; Peripheral Nervous System Diseases; Rituximab; Antibodies, Monoclonal; Immunoglobulin M; Autoantibodies; Neuritis; Biomarkers
PubMed: 37602932
DOI: 10.1002/mus.27954 -
The Medical Clinics of North America Jan 2024Acquired demyelinating syndromes (ADS) are a heterogenous group of inflammatory demyelinating conditions that include presentations of optic neuritis, transverse... (Review)
Review
Acquired demyelinating syndromes (ADS) are a heterogenous group of inflammatory demyelinating conditions that include presentations of optic neuritis, transverse myelitis, and acute demyelinating encephalomyelitis. They can be monophasic or can develop into relapsing episodes of the initial demyelinating event or evolve to include other types of demyelination. Significant progress has been made in differentiating subtypes of ADS that differ in their tendency to relapse and in which anti-inflammatory therapies are effective. Differentiating between these subtypes is important for the optimal management of these patients. Clinical features, labs (especially autoantibodies), and MRI findings can help to differentiate between the different ADS.
Topics: Humans; Magnetic Resonance Imaging; Demyelinating Diseases; Diagnosis, Differential
PubMed: 37951658
DOI: 10.1016/j.mcna.2023.05.017 -
Current Opinion in Ophthalmology Jan 2024Optic neuritis can result from several distinct causes, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte... (Review)
Review
PURPOSE OF REVIEW
Optic neuritis can result from several distinct causes, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD), when not idiopathic. This review discusses evidence-based treatment approaches contingent upon each specific cause of optic neuritis.
RECENT FINDINGS
Current evidence highlights the need for prompt plasmapheresis as adjunct to intravenous methylprednisolone (IVMP) in patients with NMOSD-associated optic neuritis. Recent advances have included a proliferation of novel disease modifying therapies (DMTs) for long-term management of NMOSD and an understanding of how existing therapeutic options can be leveraged to optimally treat MOGAD.
SUMMARY
In acute idiopathic or MS-associated optic neuritis, IVMP hastens visual recovery, though it does not substantially affect final visual outcomes. IVMP and adjunctive plasmapheresis are beneficial in the treatment of NMOSD-associated optic neuritis, with a shorter time-to-treatment associated with a higher likelihood of recovery. The natural history of untreated MOGAD-associated optic neuritis is unclear but treatment with IVMP is near-universal given phenotypic similarities with NMOSD. Long-term immunosuppressive therapy is warranted in patients with NMOSD as well as in patients with MOGAD with poor visual recovery or recurrent attacks.
Topics: Humans; Aquaporin 4; Optic Neuritis; Neuromyelitis Optica; Multiple Sclerosis; Methylprednisolone
PubMed: 37846574
DOI: 10.1097/ICU.0000000000001007 -
Clinical Microbiology Reviews Dec 2023Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is... (Review)
Review
Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.
Topics: Humans; Uveitis, Anterior; Eye Infections, Viral; Zika Virus Infection; Zika Virus; Glaucoma; Disease Progression
PubMed: 37966199
DOI: 10.1128/cmr.00057-23 -
Eye (London, England) May 2024Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder, distinct from multiple sclerosis (MS) and neuromyelitis optica... (Review)
Review
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MOGAD most frequently presents with optic neuritis (MOG-ON), often with characteristic clinical and radiological features. Bilateral involvement, disc swelling clinically and radiologically, and longitudinally extensive optic nerve hyperintensity with associated optic perineuritis on MRI are key characteristics that can help distinguish MOG-ON from optic neuritis due to other aetiologies. The detection of serum MOG immunoglobulin G utilising a live cell-based assay in a patient with a compatible clinical phenotype is highly specific for the diagnosis of MOGAD. This review will highlight the key clinical and radiological features which expedite diagnosis, as well as ancillary investigations such as visual fields, visual evoked potentials and cerebrospinal fluid analysis, which may be less discriminatory. Optical coherence tomography can identify optic nerve swelling acutely, and atrophy chronically, and may transpire to have utility as a diagnostic and prognostic biomarker. MOG-ON appears to be largely responsive to corticosteroids, which are often the mainstay of acute management. However, relapses are common in patients in whom follow-up is prolonged, often in the context of early or rapid corticosteroid tapering. Establishing optimal acute therapy, the role of maintenance steroid-sparing immunotherapy for long-term relapse prevention, and identifying predictors of relapsing disease remain key research priorities in MOG-ON.
PubMed: 38783085
DOI: 10.1038/s41433-024-03108-y -
International Journal of Molecular... Nov 2023Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort... (Review)
Review
Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Retrospective Studies; Optic Neuritis; Multiple Sclerosis; Aquaporin 4; Autoantibodies
PubMed: 37958968
DOI: 10.3390/ijms242115986