There is a wide variety of clinical-MRI phenotypes associated with MOGAD. The initially described patterns include ADEM, optic neuritis, and transverse myelitis. These can occur separately or in combination, altogether comprising more than 90% of pediatric MOGAD presentations [20,21,22]. Included are also children with neuromyelitis optica spectrum disorder-like phenotype that can present with simultaneous or sequential optic neuritis and transverse myelitis, and can exhibit other core features of neuromyelitis optica spectrum disorder such as brainstem syndrome. MOG antibodies are common in AQP4-IgG-seronegative neuromyelitis optica spectrum disorder, being reported in up to 83.4% of pediatric AQP4-IgG-seronegative patients [23, 24].

Intra-attack asymptomatic lesions can be observed in the brain, optic nerves, and spinal cord – for example, asymptomatic ADEM-like brain lesions, in a child presenting with transverse myelitis or optic neuritis. Intra-attack asymptomatic brain and optic nerve lesions have been detected in 33–50% of patients with MOGAD transverse myelitis [8], further emphasizing the importance of scanning the entire neuroaxis [15].

Over the last decade, the MOGAD umbrella has been continuously expanding to include other recognized clinical or radiological brain patterns that are not compatible with the definition of ADEM, according to the International Pediatric Multiple Sclerosis Study Group (IPMSSG) [25]. These comprise autoimmune cortical encephalitis [26], brainstem and/or cerebellar syndromes [27], leptomeningeal enhancement [28], and cerebral monofocal or polyfocal CNS deficits associated with demyelinating lesions.

Other rare presentations have been reported, mostly in adult case reports and small series, including cranial neuropathies and concomitant peripheral patterns/combined central and peripheral demyelination [8, 22, 29,30,31].

The MOGAD phenotype is age dependent, which might reflect variability in MOG expression at different age groups. Young children (<11 years) tend to present with ADEM phenotype, while older patients (≥11 years) present more commonly with optic neuritis [14, 20]. The severity of attacks and degree of recovery are also age dependent, with younger children presenting with worst clinical-radiological severity, but with faster and more complete recovery [6].

In the following subsections, MOGAD imaging findings will be described according to the involved neuroanatomic structure, and with reference to the newly diagnostic MOGAD criteria.

Brain involvement

Lesions in the brain can be associated with MOGAD ADEM, neuromyelitis optica spectrum disorder-like phenotype, autoimmune encephalitis, or brainstem/cerebellar syndromes.

MOGAD ADEM

ADEM is an encephalopathy associated with multifocal neurologic deficits (motor deficits, seizures, and cerebellar symptoms), as defined by the IPMSSG [25]. Fifty percent of children presenting with a first ADEM attack will have MOG antibodies [8, 21]. In addition, almost all patients demonstrating a relapsing course of disease, namely multiphasic disseminated encephalomyelitis or ADEM followed by optic neuritis (ADEM-optic neuritis), will be MOG antibody seropositive [13, 32].

On brain MRI, there are multifocal poorly marginated, hazy, patchy, and confluent T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities involving asymmetrically the cerebral white matter and/or gray matter, specifically the juxtacortical white matter and deep gray matter structures. The lesions might be associated with abnormal nodular enhancement. Diffusion restriction is rarely seen, mostly in younger patients, suggestive of cytotoxic edema [14, 18, 33] (Figs. 1 and 2).

Fig. 1

Acute disseminated encephalomyelitis pattern involving the brain in a 6-year-old boy with myelin oligodendrocyte glycoprotein antibody seropositivity: a–d coronal T2-weighted (a), axial fat-suppressed fluid-attenuated inversion recovery (FLAIR) (b), axial diffusion-weighted (b=1,000) (c), and corresponding apparent diffusion coefficient map (d) magnetic resonance (MR) images at initial presentation show confluent, extensive, and “fluffy” increased T2 and FLAIR signal changes involving the basal ganglia, thalami, bilateral cortices, and juxta-cortical white matter, mostly affecting the temporo-occipital regions. Few areas demonstrate diffusion restriction (arrows in c, d). e, f Axial T2-weighted MR images at initial presentation (e) and at 2-year follow-up (f) show interval volume loss of the bilateral caudate heads, putamina, and peri-insular cortices (arrows) associated with residual abnormal signal changes (asterisks)

Fig. 2

Acute disseminated encephalomyelitis (ADEM) pattern: axial fluid-attenuated inversion recovery (FLAIR) magnetic resonance images of the brain obtained from a 29-month-old boy (a, b), a 20-month-old girl (c, d), a 19-month-old boy (e, f), and a 15-month-old boy (g, h) with myelin oligodendrocyte glycoprotein antibody seropositivity, who presented with ADEM. Images at the level of the fronto-parietal lobes (a, c, e, g) and deep gray matter nuclei (b, d, f, h), show varying appearances of involvement of white matter (arrows in e) and deep gray matter structures (arrows in f)

Younger patients (<5 years) tend to present with larger lesions, including tumefactive lesions (>2 cm). They also tend to have a wider distribution of lesions, including rare involvement of the corpus callosum [14, 34, 35]. The leukodystrophy-like pattern is rarely observed, particularly in very young patients presenting with MOGAD ADEM [22, 36,37,38]. On imaging, there are extensive confluent and often symmetric T2/FLAIR-hyperintense lesions in the cerebral white matter, associated with nodular enhancement (Fig. 3).

Fig. 3

Magnetic resonance images show a leukodystrophy-like pattern in a 4-year-old girl with myelin oligodendrocyte glycoprotein antibody seropositivity, who presented with acute disseminated encephalomyelitis. a Coronal T2-weighted image shows bilateral confluent hyperintense signal changes involving asymmetrically the white matter. b Coronal fat-suppressed contrast-enhanced T1-weighted image shows bilateral nodular enhancement of the involved white matter (arrows). c Mid-sagittal T2-weighted image shows a small hyperintense lesion in the body of the corpus callosum (arrow)

Interestingly, patients presenting with MOGAD ADEM or with MOGAD neuromyelitis optica spectrum disorder-like phenotype exhibit a similar radiological pattern of widespread ADEM-like changes in the brain, despite clinical differences between the two groups [14].

Spinal cord involvement, which may affect up to 75% of MOGAD ADEM patients [14], is an important feature that can be easily overlooked in patients with encephalopathy.

Several publications have attempted to differentiate between MOGAD ADEM and seronegative ADEM based on clinical and radiological findings. They indicate that larger, more diffuse, and bilateral brain lesions, with more frequent involvement of the spinal cord, are more typical of MOGAD ADEM [32]. Nevertheless, currently a reliable differentiation between these two conditions is not possible on a routine daily basis, based only on conventional radiological features.

The imaging findings in MOGAD ADEM might overlap with POMS and AQP4+NMOSD. Features that are more suggestive of POMS include multiple, well-defined, ovoid T2/FLAIR-hyperintense lesions that asymmetrically involve the periventricular white matter and juxta/intra-cortical regions. Typically POMS lesions abut the ventricular wall perpendicularly (e.g., – Dawson fingers), with frequent involvement of the corpus callosum. Lesions may be associated with ring or open-ring enhancement [7, 33, 39] (Fig. 4). Hypointense T1-weighted lesions (“black holes”) are commonly seen in POMS, reflecting chronicity of disease [40]. Despite earlier publications describing ADEM-like lesions in POMS, it is now clear that these children had MOGAD and were misdiagnosed as multiple sclerosis prior to the antibody discovery. Multiple sclerosis in children looks exactly like multiple sclerosis in adults [23]. Of note, younger age of onset is associated with more inflammatory disease and higher lesion load. In AQP4+NMOSD, brain lesions involve primarily regions with high AQP4 expression: diencephalic regions surrounding the third ventricle and aqueduct, dorsal brainstem abutting the fourth ventricle – specifically the area postrema, and periependymal circumventricular areas. Lesions may be associated with a patchy, cloud-like pattern of enhancement, or with pencil-thin linear periependymal enhancement [7, 41,42,43,44].

Fig. 4

Magnetic resonance images obtained from three different teenagers diagnosed with pediatric-onset multiple sclerosis. a–c Brain involvement in an 11-year-old girl (a, b) and a 15-year-old girl (c). a Axial T2-weighted image shows bilateral, small, well-demarcated ovoid foci of increased T2-signal involving the subcortical and deep fronto-parietal white matter. b Axial contrast-enhanced T1-weighted image shows associated open-ring enhancement (arrow). c Sagittal fluid-attenuated inversion recovery image shows multiple high-signal foci radially oriented, perpendicular to the ventricular wall (arrows). d–f Spinal involvement in a 15-year-old boy. d Axial T2-weighted image at thoracic level shows a small hyperintense lesion involving the left lateral aspect of the spinal cord (arrow). e, f Sagittal T2-weighted (e) and fat-suppressed contrast-enhanced T1-weighted (f) images of the upper spinal cord show short-segment hyperintense T2-lesions (arrows in e), associated with nodular enhancement (arrows in f)

Involvement of the infra-tentorial structures is often associated with MOGAD ADEM, or with other MOGAD phenotypes (transverse myelitis, optic neuritis), seen with variable frequency of 10–67% in mixed pediatric and adult MOGAD cohorts [27, 45]. About two-thirds of these lesions are symptomatic, often manifesting with diplopia and ataxia [27]. Lesions in the region of the area postrema can lead to intractable hiccups, nausea, and vomiting [46]. However, this presentation is more typical of AQP4+NMOSD [15]. MRI findings of brainstem/cerebellar involvement include large ill-defined T2/FLAIR-hyperintensities, mostly involving the pons, unilateral/bilateral middle cerebellar peduncles, and/or cerebellar parenchyma [27, 47] (Figs. 5 and 6). The presence of brainstem lesions that are accompanied by large and ill-defined unilateral/bilateral middle cerebellar peduncle lesions helps in discriminating MOGAD from POMS and AQP4+NMOSD [23, 27, 45, 48, 49]. The cerebellar peduncles contain white matter tracts that are highly myelinated with abundant oligodendrocytes, which may explain the cerebellar involvement in MOGAD [15, 45].

Fig. 5

Brainstem involvement in a 17-year-old girl with myelin oligodendrocyte glycoprotein antibody-associated disease, who presented acutely with diplopia, ataxia, and left side hemiparesis. a Mid-sagittal T2-weighted, (b) axial fat-suppressed T2-weighted, and c axial fat-suppressed contrast-enhanced T1-weighted magnetic resonance (MR) images show an ill-defined lesion infiltrating the pons and right middle cerebellar peduncle (arrow in b) with mass effect on the adjacent fourth ventricle, associated with abnormal enhancement (arrow in c). d Axial fat-suppressed T2-weighted and e axial contrast-enhanced T1-weighted MR images obtained at 2-month follow-up show an interval decrease in size of the lesion (arrow in d), with resolution of enhancement (arrow in e)

Fig. 6

Cerebellar involvement in two children with myelin oligodendrocyte glycoprotein antibody-associated disease and acute disseminated encephalomyelitis. Magnetic resonance images of the brain obtained from a 20-month-old girl (a-d) and from a 15-month-old girl (e-h). a Coronal T2-weighted and (b) coronal fat-suppressed contrast-enhanced T1-weighted images show ill-defined T2-hyperintensities involving asymmetrically the bilateral cerebellar lobes (arrows in a), associated with nodular and patchy enhancement (arrows in b). c Axial fluid-attenuated inversion recovery (FLAIR) and (d) axial contrast-enhanced T1-weighted images show the lesions involving the bilateral middle cerebellar peduncles (arrows in c and d). e Coronal T2-weighted, (f) axial fat-suppressed contrast-enhanced T1-weighted, and (g, h) axial fat-suppressed contrast-enhanced FLAIR images show bilateral lesions involving the cerebellar lobes (e) and middle cerebellar peduncles (arrows in g), associated with avid confluent nodular enhancement (f-h)

In a retrospective European multicenter study, 5/36 (14%) children presenting with acute cerebellitis were seropositive to MOG antibodies [50]. On MRI, these patients had bilateral (4/5) and unilateral (1/5) involvement of the cerebellum, as well as additional supra- or infra-tentorial lesions. The clinical outcome was generally good.

Autoimmune encephalitis

This entity was first described in 2017 [51] and is commonly associated with fever, headaches, and seizures. Intra-cranial hypertension can accompany this phenotype [26, 52]. There is a higher prevalence in children, being reported in 12/89 (13.5%) pediatric-onset MOGAD, compared to 7/196 (3.6%) adults with MOGAD [53]. Three main patterns have been described: (1) Cortical encephalitis – also termed FLAIR-hyperintense lesions in anti-MOG encephalitis with seizures (FLAMES) [51, 54, 55]. On brain MRI, the T2/FLAIR-hyperintense cortical lesions can be unilateral or bilateral, diffuse, or focal. These lesions can involve the juxtacortical white matter and might be associated with leptomeningeal enhancement and/or diffusion restriction [45, 51, 53, 55] (Fig. 7). Other reported findings include swelling of the cortex with effacement of the sulci [56] (Fig. 8). Unilateral involvement affects more commonly the frontal and parietal lobes, while bilateral involvement affects commonly the frontal lobes. The occipital lobes are rarely involved [