Myelin oligodendrocyte glycoprotein antibody-associated disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rithish Nimmagadda,MBBS.[2]

Synonyms and Keywords: encephalomyelitis; Autoimmune demyelinating disease of central nervous system

Overview

An inflammatory condition of the central nervous system, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is characterized by immune-mediated demyelination assaults that mostly affect the brain, spinal cord, and optic nerves. Children are particularly vulnerable to this condition.

Historical Perspective

A protein on the surface of oligodendrocytes called myelin oligodendrocyte glycoprotein (MOG) was previously thought to be a possible target for antibodies in multiple sclerosis (MS), although preliminary research was equivocal. A significant development was the association of MOG-immunoglobulin G (IgG) with a distinct demyelinating illness in 2007. In a research utilizing MOG self-antigen tetramers found by radioimmunoassay, MOG antibodies were infrequently found in adult MS patients but were present in a subgroup of individuals with acute disseminated encephalomyelitis (ADEM).

However,With the development of newer generation cell-based tests, the MOGAD phenotype became more defined, and patients were now identified as having bouts of optic neuritis, ADEM, transverse myelitis, or other signs of the central nervous system (CNS), either alone or in combination. Distinguishing MOGAD from MS and aquaporin-4-IgG seropositive neuromyelitis optica spectrum disease (AQP4-IgG NMOSD) involved both shared and significant distinctions in terms of clinical, radiographic, and cerebrospinal fluid characteristics. As a result, MOGAD is now recognized as a unique CNS demyelinating illness.

Pathophysiology

The discovery of a disease-specific serum immunoglobulin G (IgG) antibody that selectively binds myelin oligodendrocyte glycoprotein (MOG) has led to increased understanding of a diverse spectrum of disorders, which are now termed MOGAD. Overall, the pathologic features support an antibody-mediated central nervous system (CNS) demyelinating disease distinct from multiple sclerosis (MS).

The majority of human pathology investigations on MOGAD have concentrated on the brain lesions seen during biopsy or autopsy, which has shed some light on the disease's pathophysiology. Perivenous and confluent demyelination have been shown to coexist in these investigations. Intracortical demyelinating lesions are more common than cortical demyelinating lesions. In one case series, selective MOG loss was found, but not in another. It is different from MS in that there is usually a CD4-positive T cell inflammatory response with granulocytic inflammation rather than a CD8-positive predominant infiltration. Additionally noticed is complement deposition, and reports have indicated an overlap with pattern II MS pathology.

Epidemiology and Demographics

Because myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) was just identified in 2007 and broad testing was not accessible for several years to a decade later, the epidemiology data for MOGAD are limited. As a result, the prevalence of MOGAD may have been overstated in early epidemiological data. Although research conducted in Europe imply that the incidence of MOGAD is between 1.6 and 3.4 per 1,000,000 person-years, the prevalence and incidence remain mostly unknown.

CLINICAL FEATURES

assaults that are extremely distinctive — Although none of the clinical characteristics of MOGAD are unique to the condition, several are. Among these are severe episodes of:

optic Neuritis:

● Optic neuritis, either unilateral or bilateral, causing profound vision loss ●Acute disseminated encephalomyelitis (ADEM), presenting with localized neurologic abnormalities, transverse myelitis characteristics, and impaired mental status ●Transverse myelitis, which frequently results in sensory loss, limb weakness, and problems with the bowel, bladder, or sex MOGAD may progress in a relapsing or monophasic manner.

Attacks often take days to develop, peak, and then recover in different ways over the course of weeks or months. Attacks might be preceded by a vaccine or an infectious disease.

There might be further involvement of the central nervous system (CNS), such as the clinical syndrome of neuromyelitis optica spectrum disease (NMOSD) in which there is no detectable level of aquaporin-4-immunoglobulin G (AQP4-IgG). The latter is typified by optic neuritis and transverse myelitis in any combination, occasionally with involvement of other CNS areas. Unilateral cerebral cortical encephalitis, which can cause seizures, headaches, and other focal neurologic symptoms, is another symptom that patients with MOGAD may exhibit. Although the brainstem can also be affected, this usually happens in conjunction with more extensive ADEM rather than on its own.

Any inflammatory illness or an idiopathic cause can result in optic neuritis, or inflammation of the optic nerve. While there are certain clinical signs that may indicate MOGAD, the hallmarks of optic neuritis in MOGAD are similar to those of multiple sclerosis and AQP4-IgG NMOSD. All forms of optic neuritis commonly generate pain with eye movement, and in most MOGAD instances, this occurs before to vision loss. Once more, in pediatric patients, this may be characterized as a headache, and in young children, making a precise differentiation may be difficult. With a median visual acuity at nadir of counting fingers, vision loss is usually central and severe (more severe in MOGAD than in multiple sclerosis [MS], but equivalent in severity to AQP4-IgG NMOSD).

Transverse myelitis:

This condition is characterized by inflammation across the spinal cord parenchyma, which results in neurologic impairment. It can progress over several hours or days, peaking within 21 days. This is a quick review of transverse myelitis, which is covered in more depth elsewhere.

When a person has MOGAD, their spinal cord may be affected alone or in combination with other parts of their brain. A sensory level throughout the trunk and a subacute start of paraparesis or quadriparesis with loss of feeling below the lesion are among the symptoms. In addition to erectile dysfunction in men, neurogenic bowel and bladder disorders are widespread, potentially due to frequent involvement of the conus

AQP4-IgG-seronegative NMOSD:

Given that MOGAD has been linked to both optic neuritis and LETM, it is not unexpected that between one-third and half of individuals with the clinical syndrome of NMOSD do not have aquaporin-4-IgG identified. Nevertheless, only 20 to 30 percent of MOGAD patients will meet the requirements for AQP4-IgG seronegative NMOSD, indicating the necessity for MOGAD to have its own unique set of diagnostic standards.

ADEM:

A initial polyfocal CNS episode from suspected demyelination, accompanied by encephalopathy not explained by fever, systemic disease, or postictal characteristics, characterizes this clinical condition. Large, poorly defined white matter lesions, either with or without gray matter lesions, are required MRI abnormalities. While ADEM is often monophasic, a small percentage of individuals have relapsing illness defined as multiphasic ADEM, which is characterized by numerous independent ADEM attacks; traditionally, many of these people may have had MOGAD. Thirty to fifty percent of ADEM patients have myelin oligodendrocyte glycoprotein (MOG)-IgG, and its presence may indicate a greater risk of recurrence .

other cerebral monofocal or polyfocal defects:

Neurologic abnormalities associated with MOGAD can manifest as either monofocal or polyfocal deficits, and they can progress over many hours to days. The middle cerebellar peduncle, periventricular (fourth ventricle area), supratentorial white matter, juxtacortical, cortical, and/or deep gray nuclei are the usual locations of demyelinating brain lesions that cause them. On T2-weighted MRI sequences, these lesions are hyperintense; they may or may not enhance with gadolinium. Keep in mind that periventricular lesions are less frequent in multiple sclerosis patients .

Brainstem and cerebellar features:

Compared to multiple sclerosis, isolated brainstem attacks associated with MOGAD are less prevalent. These areas are often affected as part of a multifocal CNS demyelinating onslaught that also affects other brain, optic nerve, and/or spinal cord regions. Clinical accompaniments most frequently seen include ataxia and diplopia. It is uncommon to experience a unique region postrema syndrome typical of AQP4-IgG NMOSD with isolated persistent nausea, vomiting, and hiccups, but nausea and vomiting may occur as a component of ADEM or its accompanying viral prodrome.

Cerebral cortical encephalitis  :

The condition known as cerebral cortical encephalitis is a new clinical disease that is recently identified as a MOGAD characteristic. Seizures, aphasia, stroke-like events, headaches, and fever are examples of clinical symptoms . Up to 80% of cases are unilateral, with symptoms limited to one hemisphere. Cortical edema, T2 hyperintensity, and leptomeningeal enhancement are also observed radiologically. Reports of T2 hypointensity in the surrounding white matter have also been recorded.

Children :

About half of all MOGAD event cases involve children, who appear to be susceptible to the disease. Positive MOG antibodies have been identified as a frequent finding in first presentations, and around one-third of pediatric acute acquired demyelinating syndromes have MOG-IgG.In the majority of children presenting with MOGAD, the clinical phenotype is that of ADEM, optic neuritis, or a combination of both, followed by transverse myelitis

Investigations

The following imaging and laboratory investigations are part of the initial presentation evaluation for suspected MOGAD:

●MRI, both with and without contrast of any symptomatic neuraxis area, as well as all of the following in the event that the diagnosis is unclear or encephalopathy interferes with the neurologic exam: •Images with fat saturation and orbits • Central nervous system ●MOG-IgG serum, examined by a cellular assay (see to 'MOG autoantibody' below) ●CSF analysis for routine studies (e.g., cell count, differential) and oligoclonal bands; polymerase chain reaction (PCR) testing for viral infections in selected patients; testing CSF for NMDA receptor antibodies in selected patients with features suggestive of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis (orofacial dyskinesias, psychosis, seizures).

MRI orbits:

-An MRI of the orbits, both with and without gadolinium contrast, as well as pictures showing fat saturation, commonly known as fat suppression, might provide valuable information for MOGAD. Adult cases of optic neuritis are more prevalent, and orbital MRI is a more sensitive method of diagnosing optic neuritis than brain MRI .

MRI Brain:

-Many big, fuzzy, poorly defined T2 hyperintensities of the white matter are characteristic of ADEM or ADEM-like presentations of MOGAD. deep gray matter involvement involving either one or both thalamic or basal ganglia T2 hyperintensities are widely known to help differentiate MOGAD from MS, despite the fact that AQP4-IgG NMOSD and these imaging findings overlap .

MRI of the spinal cord:

-Most patients (60 to 100 percent) with MOGAD had longitudinally significant spinal cord lesions on T2-weighted sagittal spine MRI spanning ≥3 vertebral segments. These can appear alone or in conjunction with other short or longitudinally extensive lesions; although solitary short lesions are uncommon, it is nevertheless important to rule out multiple sclerosis (MS), especially if they are peripherally placed or show a ring of enhancement.

MOG autoantibody:

A cell-based assay is used to check for serum MOG-IgG antibody. Patients with classic MOGAD clinical, MRI, and laboratory characteristics as well as those with a CNS demyelinating disease that is not consistent with multiple sclerosis should be tested. Given the possibility of false positive results, clinical judgment is needed both in the patient selection process for MOG-IgG testing as well as in the interpretation of positive data .

It is not advised to do uniform MOG-IgG testing on individuals who have clinical symptoms and MRI findings indicative of multiple sclerosis.

Given that MOG-IgG is the defining factor for MOGAD, it is imperative that doctors possess a basic understanding of the MOG-IgG test, particularly with regard to the possibility of false positive results at low titer. Here is a summary of some MOG-IgG testing guidelines and common mistakes.

Optical coherence tomography (OCT):

This is a type of imaging that uses near-infrared light to produce quantitative data on the sizes of the different layers of the retina. Since that optic neuritis is the most prevalent symptom of MOGAD in adult patients, OCT is a valuable diagnostic tool. OCT can measure the degree of previous optic nerve injury, identify previous bouts of optic neuritis, and evaluate the acute characteristics of the condition  :

●A central clinical demyelinating event being present: •Optic neuritis, as previously mentioned •Transverse myelitis (see to the section above on this condition) The disease known as acute disseminated encephalomyelitis (ADEM) (see 'ADEM' above) •deficiencies that are cerebral, either mono- or polyfocal (see 'Cerebral monofocal or polyfocal deficiencies' above) •Deficits related to the brainstem or cerebellum (see 'Brainstem and cerebellar characteristics' above) Brain cortical encephalitis, frequently accompanied by seizures (see to the sections on "Cerebral cortical encephalitis" and "Seizures" above).

●A myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) test that is considered positive when it exhibits the above-described, definite positivity.

Treatment

MEDICAL CARE

Treatment for acute attacks and techniques for preventing attacks can be used to stratify MOGAD treatment <ref name="PMID:31355308| author: Stiebel-Kalish H| title: Does time equal vision in the acute treatment of a cohort of AQP4 and MOG optic neuritis? Neurol Neuroimmunol Neuroinflamm. 2019 May 21;6(4):e572. doi: 10.1212/NXI.0000000000000572. |PMID= 31355308| url=}}</ref> .

Treatment for acute attacks: Since MOGAD acute episodes are often severe, nearly all of them are handled. It is a good idea to begin acute therapy as soon as possible since some research suggests that administering glucocorticoids early in acute assaults may avoid long-term harm.

●High-dose glucocorticoids: For five days in a row, we advise starting therapy with high-dose intravenous (IV) methylprednisolone (1000 mg for adults, 20 to 30 mg/kg daily for children). This is supported by research on idiopathic optic neuritis and multiple sclerosis (MS), and it is in line with expert panel guidelines.

Diagnosis

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