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KEY FACTS

Terminology
- Myelin oligodendrocyte glycoprotein (MOG), MOG antibody-associated disease (MOGAD)
Imaging
- Orbits - Abnormal bilateral long-segment hyperintensity of optic nerve anterior segments - Usually spares optic chiasm, retrochiasmatic pathways
- Brain - T2-hyperintense, fluffy, poorly demarcated lesions - Bilateral, large brainstem and deep gray nuclei lesions more common in children
Top Differential Diagnoses
- Multiple sclerosis
- Acute disseminated encephalomyelitis (ADEM)
- Neuromyelitis optica spectrum disorder (NMOSD)
- Brain neoplasms
- Collagen vascular disorders
- Hemophagocytic lymphohistiocytosis (HLH)
- Mitochondrial diseases
- Leukodystrophies
Pathology
- MOG protein expressed on surface of oligodendrocytes, in myelin sheath
- Cortical demyelination common, topographically adjacent meningeal inflammation
Clinical Issues
- Unilateral or bilateral optic neuritis (ON)
- Most common - Acute disseminated encephalomyelitis-like presentation with altered mental status, focal neurologic deficits - Transverse myelitis
- Less common: Cerebral cortical encephalitis - Progressive clinical decline with leukodystrophy-like MR pattern
- Infectious prodrome precedes initial symptom onset ≤ 60% of patients
Diagnostic Checklist
- Best diagnostic clue: Bilateral anterior ON + longitudinally extensive transverse myelitis (LETM)
- Evaluate optic nerves on brain imaging to identify concurrent ON
- Ovoid periventricular (Dawson fingers) lesions nottypical of MOGAD

TERMINOLOGY

Abbreviations
- Myelin oligodendrocyte glycoprotein (MOG), MOG antibody-associated disease (MOGAD)
Definitions
- Inflammatory process of CNS characterized by attacks of immune-mediated demyelination
- Clinically and laboratory distinguishable from multiple sclerosis (MS) and AQP4-IgG (+) neuromyelitis optica spectrum disorder (NMOSD)

IMAGING

General Features

Best diagnostic clue

- Bilateral **anterior** optic pathway neuritis + longitudinally extensive transverse myelitis (**LETM**)
        - Bilateral involvement during 1st optic neuritis (ON) presentation in 84% of MOGAD patients
- Brain imaging findings dependent on age at diagnosis (adult vs. child)

Location

- Orbits, cerebral hemispheres, spinal cord
- Cortical gray matter (GM)/paracortical white matter (WM) most common location for MOGAD lesions

Size
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- Variable
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CT Findings

NECT

- Hypodense lesions in areas of acute demyelination

CECT

- Variable enhancement pattern, similar to MR

MR Findings

T1WI

- ± hypointensity within brain lesions
- Not typical of "black holes" seen with MS

T2WI

- Orbits
        - Abnormal bilateral long-segment hyperintensity of optic nerve **anterior** segments
                  - Best seen on fat-saturated imaging
                  - Usually spares optic chiasm, retrochiasmatic pathways
        - Edematous, enlarged, tortuous optic nerve or nerves
        - ± optic nerve head elevation
- Brain
        - Hyperintensity in cortical GM, subcortical WM, deep WM, and deep GM
                  - Perivenous confluent pattern around small veins, lacking radiologic central vein sign (as opposed to MS)
        - Bilateral hyperintense, fluffy, poorly demarcated lesions
                  - Brain lesions present at onset < 1/2 of adults, more common in children
                  - 1/3 infratentorial, predominantly in brainstem and cerebellar peduncles (children)
                  - Ovoid periventricular (Dawson fingers) lesions **not** typical
        - Bilateral, large brainstem and deep gray nuclei lesions more common in children

STIR

- Orbits
        - Abnormal bilateral long-segment hyperintensity of anterior optic nerve segments 
                  - Spares optic chiasm, retrochiasmatic pathways
                  - ± optic nerve head elevation
- Brain
        - Same as FLAIR

FLAIR

- Orbits
        - Same as STIR
- Brain
        - Same as T2WI, lesions usually better seen
        - ± T2-hypointense subcortical WM lesions
        - Unilateral cortical **FLA**IR-hyperintense lesions in anti-**M**OG-associated encephalitis with **s**eizures (**FLAMES**)

T1WI C+

- Orbits
        - Avid optic nerve enhancement
        - Perioptic nerve sheath and surrounding orbital fat enhancement
                  - In 50-80% of MOGAD patients
- Brain
        - Variable; absent, faint, or patchy
        - Enhancement in ≈ 12% of lesions
        - ± leptomeningeal enhancement, ± adjacent cortical lesions

Imaging Recommendations

Protocol advice

- MR ± contrast of orbits, brain, and spinal cord

DIFFERENTIAL DIAGNOSIS

Multiple Sclerosis
- Optic nerves: Typically unilateral, short-segment, less extensive enhancement than MOGAD, NMOSD - ± restricted diffusion - Bilateral ON during initial presentation ≈ 23% of patients with MS-associated ON
- Brain: Presence of perpendicular periventricular lesions (Dawson fingers), "black holes"
- (+) CSF oligoclonal bands, (-) MOG antibodies, (-) AQP4 antibodies
Acute Disseminated Encephalomyelitis
- Polyfocal neurologic deficits and encephalopathy not explainable by fever
- Diffuse T2 signal abnormality in cortical GM, subcortical WM, deep WM, deep GM (or combination)
- ± linear, patchy, nodular enhancement
- May clinically mimic NMOSD and MOGAD - Clinical presentation similar to NMOSD, but AQP4 IgG (-) - Prolonged MOGAD IgG positivity suggests MOGAD
Neuromyelitis Optica Spectrum Disorder
- Most patients (+) for AQP4-IgG antibodies (seropositive NMOSD)
- Preceding infectious prodrome in ≈ 10% patients
- Optic nerves: Favors posterior optic pathway segments (optic chiasm, retrochiasmatic optic tract) - Bilateral involvement during 1st ON presentation in 82% of patients with AQP4-IgG (+) NMOSD
- Brain: Medulla oblongata (45.5%) and area postrema (31.8%) lesions most common
Brain Neoplasms
- Intracranial mass lesion - May mimic tumefactive MS on imaging
- Distinguish on clinical and imaging features
Collagen Vascular Disorders
- Systemic lupus erythematosus, Sjögren syndrome neuro-Behçet disease, neurosarcoidosis
- Look for elevated markers of systemic inflammation - Abnormal antinuclear antibody profile, (+) double-stranded DNA antibodies, elevated angiotensin converting enzyme, and (+) antiphospholipid antibodies
Hemophagocytic Lymphohistiocytosis
- Primary involvement of CNS (rarely) precedes systemic manifestations of hemophagocytic lymphohistiocytosis (HLH)
- Pediatric CNS-isolated HLH can mimic acute disseminated encephalomyelitis (ADEM) clinically and on imaging
Mitochondrial Diseases
- Typical MR features include abnormal T2 hyperintensity in basal ganglia or parietooccipital regions
- (Mitochondrial) myopathy, encephalopathy, lacticacidosis, and stroke-like episodes syndrome (MELAS), Leigh disease, others
- Elevation of serum and CSF lactate levels
Leukodystrophies
- Metachromatic leukodystrophy (MLD), X-linked adrenoleukodystrophy (ALD), Alexander disease (AD), Krabbe disease (globoid cell leukodystrophy)
- Look for characteristic imaging or laboratory abnormalities

PATHOLOGY

General Features
- MOG is myelin protein expressed on outer surface of oligodendrocytes and myelin sheath - Function not known; may act as cell adhesion molecule, regulate microtubule stability, and modulate myelin immune interactions
- Cortical demyelination common, topographically associated with adjacent meningeal inflammation
- Intracortical > subcortical WM demyelinated lesions predominate (compared to MS)
- MOG-IgG present in ~ 1/3 of pediatric acute acquired demyelinating syndromes
Staging, Grading, & Classification
- New diagnostic criteria for MOGAD (March 2023) - Intended to improve MOGAD identification, distinguish it from other disorders with overlapping clinical features, such as NMOSD, MS - 3 primary diagnostic criteria - 1 of 6 core clinical demyelinating events [i.e., ON, transverse myelitis (TM), ADEM-like encephalopathy, cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, or cerebral cortical encephalitis] - MOG-immunoglobulin G (IgG) antibody test (+) - In absence of serum positivity for MOG-immunoglobulin G (IgG) by cell-based assay, CSF positivity for MOG-IgG fulfills criteria - Exclusion of better diagnosis
Microscopic Features
- Initial peripheral T-cell activation of T cells → reactivation in subarachnoid/perivascular spaces by MOG-laden antigen-presenting cells and inflammatory CSF milieu - T cells, granulocytes cross blood brain barrier, infiltrate CNS parenchyma - Macrophages/microglia appear in lesions
- Anti-MOG antibodies opsonize MOG, activate complement- and antibody-dependent cellular cytotoxicity
- CD4 (+) T-cell and granulocytic inflammation typical - CD8 (+) T-cell infiltrate typical in MS
- Perivenous confluent pattern around small veins - Coexisting perivenous and confluent demyelination + cortical demyelination - Intracortical demyelinating lesions predominate
- Extensive subpial cortical demyelination with microglial activation, inflammatory infiltrate
- Affects oligodendrocytes but spares astrocytes (unlike NMOSD) - Oligodendroglial progenitor cells spared because they do not yet express MOG
- Chronic active lesions absent
Laboratory Evaluation
- Serum MOG-IgG antibody testing by cell-based assay
- Serum AQP4-IgG testing to exclude NMOSD
- CSF testing for oligoclonal bands to evaluate for MS

CLINICAL ISSUES

Presentation

Most common signs/symptoms

- Unilateral or bilateral ON
        - Varying degrees of vision loss + eye pain worsened with eye movement
        - Most common clinical MOGAD manifestation at onset
        - Visual loss typically central and severe (more severe in MOGAD than MS, similar in severity to NMOSD
        - Opticospinal phenotype increases in frequency as children get older
- ADEM-like presentation with altered mental status, focal neurologic deficits
        - Up to 68% of cases at initial presentation
        - Some MOGAD patients have clinical and MR features of ADEM but not encephalopathy
        - Recurrence of ADEM features after recovery suggests MOGAD
- TM
        - Limb weakness, sensory loss, and bowel, bladder, or sexual dysfunction
- Cerebral cortical encephalitis
        - Headache, seizures, stroke-like episodes, and focal neurologic deficits
        - Seizures more common than with NMOSD and MS

Other signs/symptoms

- Rare: Progressive clinical decline with leukodystrophy-like MR pattern

Clinical profile

- Most common pediatric clinical phenotype is ADEM-like encephalopathy, ON (or both), followed by TM

Demographics

Age

- Predilection for children but can affect any age
        - Median age of MOGAD onset: 20-30 years
        - Children: ≈ 50% of MOGAD cases

Sex
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- M = F
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Epidemiology

- Incidence and prevalence largely unknown
        - European studies suggest incidence 1.6-3.4 per 1,000,000 person-years

Natural History & Prognosis
- Infectious prodrome precedes initial symptom onset ≤ 60% of patients
- Monophasic or relapsing course (≈ 50/50) - ON is most common relapse manifestation (followed by TM)
- Attacks develop over days, plateau with variable recovery over weeks to months
- Most T2 lesions resolve completely over months to few years - Useful discriminator from MS and AQP4-IgG NMOSD, in which majority have residual T2-hyperintense lesions
- MOG-associated ON generally responds well to steroid administration - Optic nerve edema and enlargement may resolve with residual T2 hyperintensity and optic nerve atrophy
- Visual outcomes after MOG-associated ON better than NMOSD
- Long-term disability rates lower than with NMOSD or MS - MOGAD not associated with primary or secondary progressive course
- Low mortality
Treatment
- Glucocorticoid therapy 1st line

DIAGNOSTIC CHECKLIST

Consider
- Simultaneous bilateral ON involving anterior optic pathway with associated optic disc edema strongly implies MOGAD
Image Interpretation Pearls
- Evaluate optic apparatus carefully on brain imaging to identify concurrent ON

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References

Selected References

Images

Selected Images

Axial FLAIR MR in a 10-year-old with acute myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) shows characteristic thalamic , basal ganglia , hypothalamic , and insular cortex hyperintense lesions. The hypothalamic lesions are relatively subtle but correlated clinically with lethargy and hypothalamic symptoms and signs.

Axial FLAIR MR in the same patient additionally reveals brainstem/cerebellar peduncle , deep cerebellar white matter , and cerebellar hemisphere lesions.

Axial T1 C+ FS MR in the same patient shows patchy enhancement of the thalamic, basal ganglia, and hypothalamic lesions. In this patient, the hypothalamic lesions are conspicuous on contrast imaging but subtle on noncontrast FLAIR MR.

Axial T1 C+ FS MR in the same patient 3 months prior reveals avid contrast enhancement of the left optic nerve (anterior segment) . Laboratory assessment at that time confirmed MOG antibodies, but brain imaging was normal (not shown).

Axial FLAIR MR in a 4-year-old with florid optic neuritis and encephalopathy with positive anti-MOG antibody titer reveals abnormal hyperintensity and swelling within the bilateral basal ganglia , insular cortex , perventricular white matter, and posterior thalami.

Axial T1 C+ FS MR in the same patient reveals minimal, if any, enhancement within the same abnormal brain regions.

Axial FLAIR MR in a 4-year-old with severe onset of encephalopathy with positive MOG antibody titer depicts several areas of abnormal cortical hyperintensity and edema as well as subcortical white matter signal abnormalities.

Axial T1 C+ FS MR in the same patient reveals subtle leptomeningeal enhancement over the right parietal lobe. This constellation of findings represents cerebral cortical encephalitis, a finding unique to MOGAD and potentially predisposing to seizures.

Axial FLAIR MR in a 5-year-old patient with florid encephalopathy and emesis reveals multifocal T2-hyperintense lesions predominantly localizing to the brainstem and posterior fossa. Lesions are noted in the middle cerebellar peduncles, deep cerebellar white matter, and dorsal brainstem near the facial colliculus (area postrema, explaining vomiting).

Axial T1 C+ FS MR in the same patient reveals patchy partial ring and nodular enhancement in these abnormal areas.

Additional Images

Axial FLAIR MR in a 7-year-old patient with MOGAD reveals subcortical white matter and deep nuclear gray matter involvement. This is a fairly typical appearance for MOGAD MR abnormalities.

Axial FLAIR MR in the same patient confirms patchy brainstem signal abnormality as well. This patient also presented with severe transverse myelopathy with longitudinally extensive transverse myelitis (LETM) pattern on spine MR (not shown).

Coronal T2 MR through the frontal lobes of a pediatric patient with encephalopathy, optic neuritis, and confirmed MOGAD reveals abnormal hyperintensity within the left basal ganglia as well as mild hyperintensity in the left cisternal optic nerve .

Coronal T1 C+ FS MR in the same patient shows no enhancement in the slightly hypointense basal ganglia lesion , but avid enhancement of both cisternal optic nerves (bilateral anterior segment optic neuritis). Contrast is essential for assessing the optic nerves for signs of neuritis.

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KEY FACTS

Terminology

Imaging

Top Differential Diagnoses

Pathology

Clinical Issues

Diagnostic Checklist

TERMINOLOGY

Abbreviations

Definitions

IMAGING

General Features

Best diagnostic clue

Location

Size

CT Findings

NECT

CECT

MR Findings

T1WI

T2WI

STIR

FLAIR

T1WI C+

Imaging Recommendations

Protocol advice

DIFFERENTIAL DIAGNOSIS

Brain Neoplasms

Collagen Vascular Disorders

Hemophagocytic Lymphohistiocytosis

Mitochondrial Diseases

Leukodystrophies

PATHOLOGY

General Features

Staging, Grading, & Classification

Microscopic Features

Laboratory Evaluation

CLINICAL ISSUES

Presentation

Most common signs/symptoms

Other signs/symptoms

Clinical profile

Demographics

Age

Sex

Epidemiology

Natural History & Prognosis

Treatment

DIAGNOSTIC CHECKLIST

Consider

Image Interpretation Pearls

References

Selected References

Images

Selected Images

Additional Images

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