Long-term outcomes of ADEM-like and tumefactive presentations of CNS demyelination: a case-comparison analysis

Abstract

A minority of initial multiple sclerosis (MS) presentations clinically or radiologically resemble other central nervous system (CNS) pathologies, acute disseminated encephalomyelitis (ADEM) or tumefactive demyelination (atypical demyelination presentations). With the aim of better defining the long-term outcomes of this group we have performed a retrospective cohort comparison of atypical demyelination versus 'typical' MS presentations. Twenty-seven cases with atypical presentations (both first and subsequent demyelinating events) were identified and compared with typical MS cases. Disease features analysed included relapse rates, disability severity, whole brain and lesion volumes, lesion number and distribution. Atypical cases represented 3.9% of all MS cases. There was considerable overlap in the magnetic resonance imaging (MRI) features of ADEM-like and tumefactive demyelination cases. ADEM-like cases tended to be younger but not significantly so. Atypical cases showed a trend towards higher peak expanded disability severity score (EDSS) score at the time of their atypical presentation. Motor, cranial nerve, cerebellar, cerebral and multifocal presentations were all more common in atypical cases, and less likely to present with optic neuritis. Cerebrospinal fluid (CSF) white cell counts were higher in atypical cases (p = 0.002). One atypical case was associated with peripheral blood myelin oligodendrocyte glycoprotein (MOG) antibodies, but subsequent clinical and radiological course was in keeping with MS. There was no difference in long-term clinical outcomes including annualised relapse rates (ARR), brain volume, lesion numbers or lesion distributions. Atypical demyelination cases were more likely to receive high potency disease modifying therapy early in the course of their illness. Despite the severity of initial illness, our cohort analysis suggests that atypical demyelination presentations do not confer a higher risk of long-term adverse outcomes.

Keywords: Acute disseminated encephalomyelitis; Multiple sclerosis; Prognosis; Tumefactive.

Fig. 1

MRI of ADEM-like and tumefactive MS cases. Images are paired (matched slices) with FLAIR images in first and third vertical panels and Gd-enhanced T1 weighted sequences in second and fourth vertical panels. Case of ADEM-like lesions with small and large lesions which all show Gadolinium enhancement (A–D), one larger lesion (D arrow) shows ring-enhancement with central hypointensity and peri-lesional hypointensity with surrounding oedema. Case of ADEM-like lesions with a multitude of smaller lesions all of which show either homogeneous or ring enhancement (E–H). Case of ADEM with multiple large lesions showing both ring enhancement and heterogeneous enhancement. Case of ADEM-like lesions showing multiple small and large lesions (M–N). Some lesions are non-enhancing, with some having central hypointensity on T1 sequences (M and O open arrows) whilst other lesions show ring-enhancement (open arrows). Case of recurrent tumefactive MS showing large incomplete ring-enhancing lesion with central hypointensity and surrounding oedema (solid arrow) with mass effect (S and T). Case of tumefactive MS with a large incomplete ring-enhancing lesion (solid arrow) with central and perilesional hypointensity and a second non-enhancing lesion (open arrow) with central hypointensity (S and T)

Fig. 2

Three patterns of lesion in ADEM-like lesions. Vertical panels show FLAIR sequences (right), diffusion weighted images (centre) and T1 with contrast (left). Horizontal panels show individual cases. Upper panel (A–C) shows case with FLAIR and DWI hyperintensity with T1 hypointensity, but no Gd-enhancement. Middle panel (D–F) shows ring pattern hyperintensity on FLAIR and DWI with central hypointensity and ring-enhancement on T1 sequence. Lower panel (G–I) shows predominantly heterogeneous FLAIR and DWI hyperintensity with heterogeneous Gd-enhancement. There are additional lesions showing central T1 hypointensity and no enhancement.

Fig. 3

Survival curves from cox-proportional hazard models for time to first relapse (A) and time to reach EDSS 6.0 (B). Age, sex and initial treatment (low, medium or high efficacy) were included in the model. EDSS expanded disability status scale

Fig. 4

Box and whisker plots of number of T2/FLAIR lesions (A), T2 lesion volume (B) and whole brain volume (C) at presentation of atypical attack (Onset), 2 years, 5 years and last MRI (Final), change in whole brain volume (brain atrophy) compared to baseline at 2 year, 5 year and final follow up (D), Number of Gadolinium enhancing lesions at onset and final follow up (E), and number of T2/FLAIR lesions at onset for MS, ADEM-like and tumefactive cases (F). Significant differences between atypical and typical MS cases are indicated. Central bar shows median, box shows interquartile range and whiskers indicate range. Outliers indicated by circles; extreme outliers indicated by asterisks

Fig. 5

Box and whisker plots of distribution of T2/FLAIR lesions at presentation (A) and last follow up (B). Significant differences between atypical and typical MS cases are indicated. Central bar shows median, box shows interquartile range and whiskers indicate range. Outliers indicated by circles; extreme outliers indicated by asterisks. Subcort subcortical; Perivent periventricular; Brainste brainstem; Cerebell Cerebellar; Cer Ped cerebellar peduncle