Explore the vast range of titles available.

Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is now recognised as a nosological entity with specific clinical and paraclinical features to aid early diagnosis. Although no age group is exempt, median age of onset is within the fourth decade of life, with optic neuritis being the most frequent presenting phenotype. Disease course can be either monophasic or relapsing, with subsequent relapses most commonly involving the optic nerve. Residual disability develops in 50–80% of patients, with transverse myelitis at onset being the most significant predictor of long-term outcome. Recent advances in MOG antibody testing offer improved sensitivity and specificity. To avoid misdiagnosis, MOG antibody testing should be undertaken in selected cases presenting clinical and paraclinical features that are felt to be in keeping with MOG-AD, using a validated cell-based assay. MRI characteristics can help in differentiating MOG-AD from other neuroinflammatory disorders, including multiple sclerosis and neuromyelitis optica. Cerebrospinal fluid oligoclonal bands are uncommon. Randomised control trials are limited, but observational open-label experience suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and for immunosuppressive therapies, such as steroids, oral immunosuppressants and rituximab as maintenance treatment.

Optic neuritis is an inflammatory optic neuropathy that is commonly indicative of autoimmune neurological disorders including multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease, and neuromyelitis optica spectrum disorder. Early clinical recognition of optic neuritis is important in determining the potential aetiology, which has bearing on prognosis and treatment. Regaining high-contrast visual acuity is common in people with idiopathic optic neuritis and multiple sclerosis-associated optic neuritis; however, residual deficits in contrast sensitivity, binocular vision, and motion perception might impair vision-specific quality-of-life metrics. In contrast, recovery of visual acuity can be poorer and optic nerve atrophy more severe in individuals who are seropositive for antibodies to myelin oligodendrocyte glycoprotein, AQP4, and CRMP5 than in individuals with typical optic neuritis from idiopathic or multiple-sclerosis associated optic neuritis. Key clinical, imaging, and laboratory findings differentiate these disorders, allowing clinicians to focus their diagnostic studies and optimise acute and preventive treatments. Guided by early and accurate diagnosis of optic neuritis subtypes, the timely use of high-dose corticosteroids and, in some instances, plasmapheresis could prevent loss of high-contrast vision, improve contrast sensitivity, and preserve colour vision and visual fields. Advancements in our knowledge, diagnosis, and treatment of optic neuritis will ultimately improve our understanding of autoimmune neurological disorders, improve clinical trial design, and spearhead therapeutic innovation.

ObjectiveWe characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.MethodsWe evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients.ResultsThe most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077).ConclusionRelapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.

Optic neuritis (ON), an inflammatory optic neuropathy, is among the most common causes of visual loss. In its initial clinical appearance, ON may have unilateral or bilateral presentation, and anterior (papillitis) or retrobulbar localization. Traditionally, cases are divided into typical and atypical ON. In the Western hemisphere, most typical cases of optic nerve inflammation are associated with multiple sclerosis (MS). However, ON may also be associated with a series of disorders of known or initially undetected origin. Atypical ON has a somewhat different clinical picture from typical ON, and encompasses neuromyelitis optica spectrum disease (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic recurrent neuroretinitis (NR), chronic relapsing inflammatory ON (CRION), ON within systemic autoimmune diseases, paraneoplastic and neuritis during or after infectious diseases or vaccination. The causes should be meticulously worked up, to address the therapeutic and prognostic challenges posed by these conditions. Here, we provide a brief overview of atypical ON, as encountered in our clinical practice, and additionally discuss the possible occurrence of optic neuropathies other than inflammatory and other ocular diseases within these disorders.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

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.

Guillain-Barré syndrome (GBS) is a devastating autoimmune disease of the peripheral nervous system (PNS) with limited treatment options. Several studies have shown attenuation of the well-characterized GBS preclinical experimental autoimmune neuritis (EAN) model with systemically administered therapeutic compounds via anti-inflammatory or immunomodulatory mechanisms. Despite this, clinical advancement of these findings is limited by dosing that is not translatable to humans or is associated with off-target and toxic effects. This is due, in part, to the blood-nerve barrier (BNB), which restricts access of the circulation to peripheral nerves. However, during acute neuroinflammation, the normally restrictive BNB exhibits increased vascular permeability and enables immune cell infiltration. This may offer a unique window to access the otherwise restricted peripheral nerve microenvironment for therapeutic delivery. Here, we assessed the degree to which BNB permeability and immune cell infiltration over the course of EAN enables accumulation of circulating nanoparticles. We found that at disease stages defined by distinct clinical scores and pathology (onset, effector phase, and peak of EAN severity), intravenously administered small molecules and nanoparticles ranging from 50 to 150 nm can permeate into the endoneurium from the endoneurial vasculature in a size- and stage-dependent manner. This permeation occurs uniformly in both sciatic nerves and in proximal and distal regions of the nerves. We propose that this nerve targeting enabled by pathology serves as a platform by which potential therapies for GBS can be reevaluated and investigated preclinically in nanoparticle delivery systems.

Purpose Optic neuritis (ON) is a relatively common ophthalmic disease that has recently received renewed attention owing to immunological breakthroughs. We studied the profile of patients with ON with special reference to antibody-mediated ON and the challenges faced in its management. Methods Case records of patients with ON presenting to a tertiary eye-care center in South India were analyzed. Data on demographics, presenting visual acuity (VA), clinical features, seropositivity for aquaporin-4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), details of magnetic resonance imaging (MRI) of orbits and brain, and treatment were collected. Results Among 138 cases with acute ON, male: female ratio was 1:2. Isolated ON was present in 41.3% of cases. Antibody testing of sera was performed in 68 patients only due to financial limitations. Among these, 48.5% were MOG-IgG-seropositive, 11.76% were AQP4-IgG-seropositive, and 30.88% samples were double seronegative. Other causes included multiple sclerosis (n = 4), lactational ON (n = 4), tuberculosis (n = 2), invasive perineuritis (n = 2), COVID-19 vaccination (n = 2), and COVID-19 (n = 1). The mean presenting best corrected visual acuity (BCVA) was 1.31 ± 1.16 logMAR (logarithm of the minimum angle of resolution). The mean BCVA at 3 months was 0.167 ± 0.46 logMAR. Only initial VA ≤ ‘Counting fingers’ (CF) had a significant association with the visual outcome for final VA worse than CF. The steep cost of investigations and treatment posed challenges for many patients in the management of ON. Conclusion MOG-IgG-associated ON is common in India. Unfortunately, financial constraints delay the diagnosis and timely management of ON, adversely affecting the outcome.

Chronic relapsing inflammatory optic neuropathy (CRION) is an entity that was described in 2003. Early recognition of patients suffering from CRION is relevant because of the associated risk for blindness if treated inappropriately. It seems timely to have a clinical review on this recently defined entity. A systematic literature review, irrespective of language, retrieved 22 case series and single reports describing 122 patients with CRION between 2003 and 2013. We review the epidemiology, diagnostic workup, differential diagnosis, and treatment (acute, intermediate, and long term) in view of the collective data. These data suggest that CRION is a distinct nosological entity, which is seronegative for anti-aquaporin four auto-antibodies and recognized by and managed through its dependency on immuno-suppression. Revised diagnostic criteria are proposed in light of the data compromising a critical discussion of relevant limitations.

Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) ( p  = 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group ( p  = 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.