Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis

Abstract

Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those of multiple sclerosis and AQP4 antibody disease. The aim of this study was to identify brain imaging discriminators between those three inflammatory central nervous system diseases in adults and children to support diagnostic decisions, drive antibody testing and generate disease mechanism hypotheses. Clinical brain scans of 83 patients with brain lesions (67 in the training and 16 in the validation cohort, 65 adults and 18 children) with MOG antibody (n = 26), AQP4 antibody disease (n = 26) and multiple sclerosis (n = 31) recruited from Oxford neuromyelitis optica and multiple sclerosis clinical services were retrospectively and anonymously scored on a set of 29 predefined magnetic resonance imaging features by two independent raters. Principal component analysis was used to perform an overview of patients without a priori knowledge of the diagnosis. Orthogonal partial least squares discriminant analysis was used to build models separating diagnostic groups and identify best classifiers, which were then tested on an independent cohort set. Adults and children with MOG antibody disease frequently had fluffy brainstem lesions, often located in pons and/or adjacent to fourth ventricle. Children across all conditions showed more frequent bilateral, large, brainstem and deep grey matter lesions. MOG antibody disease spontaneously separated from multiple sclerosis but overlapped with AQP4 antibody disease. Multiple sclerosis was discriminated from MOG antibody disease and from AQP4 antibody disease with high predictive values, while MOG antibody disease could not be accurately discriminated from AQP4 antibody disease. Best classifiers between MOG antibody disease and multiple sclerosis were similar in adults and children, and included ovoid lesions adjacent to the body of lateral ventricles, Dawson's fingers, T1 hypointense lesions (multiple sclerosis), fluffy lesions and three lesions or less (MOG antibody). In the validation cohort patients with antibody-mediated conditions were differentiated from multiple sclerosis with high accuracy. Both antibody-mediated conditions can be clearly separated from multiple sclerosis on conventional brain imaging, both in adults and children. The overlap between MOG antibody oligodendrocytopathy and AQP4 antibody astrocytopathy suggests that the primary immune target is not the main substrate for brain lesion characteristics. This is also supported by the clear distinction between multiple sclerosis and MOG antibody disease both considered primary demyelinating conditions. We identify discriminatory features, which may be useful in classifying atypical multiple sclerosis, seronegative neuromyelitis optica spectrum disorders and relapsing acute disseminated encephalomyelitis, and characterizing cohorts for antibody discovery.

Magnetic resonance imaging diagnosis of demyelinating diseases: An update

“…Typically, lesions appear as a small number (≤3) of poorly demarcated infratentorial lesions, 103 and thalamic and pontine lesions are distinctive MRI findings. 104 Supratentorial deep white matter lesions can be seen (Fig.…”

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: practical considerations

“…From left to right: lesion on a sagittal T2-weighted image, ring-like gadolinium enhancement on a T1-weighted image and central cord involvement on an axial T2-weighted scan. Further examples of myelin oligodendrocyte glycoprotein-antibody associated lesions are found in ref 29 .…”

“…MOG antibody disease can also present with isolated brainstem attacks, which are associated with fluffy brainstem lesions on MRI, typically located in the pons, medulla or cerebellar peduncles, and often adjacent to the fourth ventricle 29. Brainstem involvement might also be part of a severe presentation involving LETM and optic neuritis 31.…”

“…Brainstem involvement might also be part of a severe presentation involving LETM and optic neuritis 31. The brain lesions in MOG antibody disease are difficult to distinguish from AQP4 antibody NMOSD but are distinct from MS 29. Although dorsal medullary and area postrema attacks (with associated lesions) have been considered pathognomonic for AQP4 antibody NMOSD, these can occur in MOG antibody patients16 32 and may be the onset presentation; however, a ‘full house’ area postrema attack (with intractable nausea, vomiting and hiccups) is still more common in AQP4 antibody disease.…”

Clinical and imaging correlation in patients with pathologically confirmed tumefactive demyelinating lesions

“…Serum testing for antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) was not available for any of the subjects in our cohort. While the importance of anti-MOG testing in NMO spectrum disorders and other demyelinating disease phenotypes including TDLs has since been highlighted in emerging literature,[24] MOG testing was not performed in any of these patients and was not clinically available during the epoch under study. Glucocorticoids were administered in 69% of patients (70% after biopsy, 20.7% at various time points before biopsy).…”