Relapsing Demyelinating Syndromes in Children: A Practical Review of Neuroradiological Mimics

Abstract

Relapsing demyelinating syndromes (RDS) in children encompass a diverse spectrum of entities including multiple sclerosis (MS) acute disseminated encephalomyelitis (ADEM), aquaporin-4 antibody associated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). In addition to these, there are "antibody-negative" demyelinating syndromes which are yet to be fully characterized and defined. The paucity of specific biomarkers and overlap in clinical presentations makes the distinction between these disease entities difficult at initial presentation and, as such, there is a heavy reliance on magnetic resonance imaging (MRI) findings to satisfy the criteria for treatment initiation and optimization. Misdiagnosis is not uncommon and is usually related to the inaccurate application of criteria or failure to identify potential clinical and radiological mimics. It is also notable that there are instances where AQP4 and MOG antibody testing may be falsely negative during initial clinical episodes, further complicating the issue. This article illustrates the typical clinico-radiological phenotypes associated with the known pediatric RDS at presentation and describes the neuroimaging mimics of these using a pattern-based approach in the brain, optic nerves, and spinal cord. Practical guidance on key distinguishing features in the form of clinical and radiological red flags are incorporated. A subsection on clinical mimics with characteristic imaging patterns that assist in establishing alternative diagnoses is also included.

Keywords: ADEM; AQP4; MOG; MS; demyelimating disease; mimics; multiple scleorsis; pediatric.

Figure 1

Typical appearances of RDS in children. MS—top row (A–D) Juxtacortical, periventricular and infratentorial brain lesions are readily appreciated on coronal T2-FLAIR (A) and sagittal T2-weighted images (B). In the spine there are short segment eccentric lesions appreciated on sagittal and axial T2-weighted images (C,D, respectively). MOG-AD—middle row (E–H) Large confluent lesions with ill-defined enhancement are demonstrated within the brain on coronal T2-FLAIR (E) and contrast-enhanced sagittal T1-weighted images (F). In the spine, there are lesions involving gray and white matter on sagittal and axial T2-weighted images (G,H, respectively). AQP4-NMOSD—bottom row (I–L) Brain lesions are present in areas of AQP4 expressivity. For example, in this case there is involvement of the area postrema on coronal T2-FLAIR (I) and sagittal T2-weighted images (J). A lesion is also present in the upper spinal cord. In the spine there is longitudinally extensive transverse myelitis on sagittal and axial T2-weighted images (K,L, respectively).

Figure 2

Mimics of RDS with discrete brain lesions. All these lesions on first glance could mimic RDS on the basis of imaging alone. However, the lesions do not strictly satisfy the McDonald criteria. Clinical history and follow up is therefore also vital in reaching a correct diagnosis. (A) NOTCH3 mutation: Axial T2-FLAIR imaging demonstrates small discrete lesions in the white matter of both cerebral hemispheres. (B) Leber's hereditary optic neuropathy: Coronal T2-FLAIR imaging reveals a discrete brain lesion in the right hemispheric white matter. The optic nerves were also atrophic (not shown). (C) Incontinentia pigmenti: Axial T2-weighted images demonstrate white matter lesions in the centrum semiovale bilaterally. There is also volume loss within the left frontal lobe. (D) Migraine: Coronal T2-FLAIR imaging demonstrates small discrete lesions in the frontal white matter bilaterally. These were stable on follow up and there were no clinical features of demyelination. (E) Hereditary spastic paraparesis: Coronal T2-FLAIR demonstrates thinning of the anterior corpus callosum and periventricular signal abnormality—“ears of the lynx” sign. There were no juxtacortical lesions.

Figure 3

Mimics of RDS with confluent brain lesions. (A) Acute haemorrhagic leukoencephalopathy: Confluent white matter lesion in the left frontal lobe with intralesional hemorrhage extending into the corpus callosum. There was patchy enhancement of this lesion (not shown). Salmonella infection was confirmed on serology. (B) Complex 1 deficiency mitochondriopathy: Confluent white matter lesions of both cerebral hemispheres which demonstrated cavitation and restricted diffusion (not shown). (C) Giant axonal neuropathy due to exon 1 deletion of GAN gene: Axial T2-weighted image illustrates signal abnormality within the frontoparietal white matter and parenchymal volume loss. (D) Subacute sclerosing panencephalitis: White matter signal abnormality is noted within the parietal lobes bilaterally, but is more extensive in the left cerebral hemisphere where there is blurring of the gray-white matter margin. (E) Anti NMDA receptor antibody encephalitis: Axial FLAIR imaging demonstrates signal abnormality within the caudate nuclei bilaterally, the right putamen and left globus pallidus. There is also involvement of the right sided subinsular white matter and posterior limb of the internal capsule. The appearances could be mistaken for ADEM. (F) Glioma: Axial T2-weighted image demonstrates white matter signal change in the left temporal lobe with swelling of the cortex. This was followed up, and subsequently biopsied due to growth and enhancement.

Figure 4

Optic nerve mimics of RDS. (A,B) Optic pathway glioma: The coronal T1-weighted image with contrast shows an expanded intra-orbital right optic nerve. The optic chiasm is expanded on T2-weighted axial imaging (B). (C,D) Optic nerve sheath meningioma: On coronal STIR (C) and coronal T1-weighted image with contrast (D) there is thickening and enhancement of the right optic nerve sheath complex. (E,F) Orbital sarcoidosis: On coronal STIR (E) and coronal T1-weighted image with contrast (F) there is stranding of the intraconal fat, minimal perineural thickening and enhancement.

Figure 5

Mimics in the spine—short segment spinal lesions. (A) Infectious myelitis secondary to cytomegalovirus: Multifocal short segment T2 hyperintense lesions are noted in the cervical and upper thoracic cord. (B) Neurofibromatosis 1: Intramedullary foci of abnormal signal intensity (FASI). (C,D) Hemophagocytic Lymphohistiocytosis: Short segment enhancing lesions. These have a more punctate morphology.

Figure 6

Mimics in the spine—longitudinally extensive spinal lesions. (A) Rhombencephalomyelitis: This was confirmed as mycoplasma on serological testing. (B) Biotinidase deficiency: Confirmed on genetic and enzymatic testing in a child with skin rash, seizures and alopecia. The appearances are similar to those seen on the RDS spectrum LETM however the clinical features are not typical of RDS. (C) Fibrocartilaginous embolism: Note the signal abnormality in the cord as a result of infarction. There was restricted diffusion within the lesion (not shown). The likely source was the C3/4 intervertebral disc which demonstrates a reduction in signal (white arrow).