Defining the natural history of tumefactive demyelination: A retrospective cohort of 257 patients

Abstract

ObjectiveTo describe demographic, clinical, and radiographic features of tumefactive demyelination (TD) and identify factors associated with severe attacks and poor outcomes.MethodsRetrospective review of TD cases seen at Mayo Clinic, 1990–2021.ResultsOf 257 patients with TD, 183/257 (71%) fulfilled the 2017 multiple sclerosis (MS) McDonald criteria at the last follow‐up, 12/257 (5%) had myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD), 0 had aquaporin‐4‐IgG seropositive neuromyelitis optic spectrum disorders (AQP4+ NMOSD), and 62/257 (24%) were cryptogenic. Onset before age 18 was present in 18/257 (7%). Female to male ratio was 1.3:1. Cerebrospinal fluid oligoclonal (CSF) bands were present in 95/153 (62%). TD was the first demyelinating attack in 176/257 (69%). At presentation, 59/126 (47%) fulfilled Barkhof criteria for dissemination in space, 59/100 (59%) had apparent diffusion coefficient (ADC) restriction, and 57/126 (45%) had mass effect. Despite aggressive clinical presentation at onset, 181/257 (70%) of patients remained fully ambulatory (Expanded Disability Status Scale [EDSS] ≤4) after a 3.0‐year median follow‐up duration. Severe initial attack‐related disability (EDSS ≥4) was more common in patients with motor symptoms (81/143 vs. 35/106, p < 0.0001), encephalopathy (20/143 vs. 2/106, p < 0.0001) and ADC restriction on initial MRI (42/63 vs. 15/33, p = 0.04). Poor long‐term outcome (EDSS ≥4) was more common in patients with older onset age (41.9 ± 15 vs. 36.8 ± 15.6, p = 0.02) and motor symptoms at onset (49/76 vs. 66/171, p < 0.0001).InterpretationMost TD patients should be considered part of the MS spectrum after excluding MOGAD and NMOSD. Motor symptoms and older age at presentation portend a poor outcome.

Tumefactive Demyelinating Lesions: An Illustrative Pediatric Case With an Atypical Presentation and Literature Review

“…If a lumbar puncture can be performed, CSF shows slightly elevated protein levels and mild pleocytosis but can be completely normal [ 1 , 4 , 5 , 8 ], as was the case with our patient. Oligoclonal bands (OCB) are positive in about half of the patients with TDLs, some of which develop MS on follow-up.…”

“…First described in 1979 in a patient with MS [ 6 ], TDLs were then conceptualized as being either an MS variant or a disease entity on a spectrum between MS and ADEM [ 7 ]. Today, TDLs have been reported in the literature associated with a variety of acquired CNS demyelinating diseases including MS and its atypical variants, ADEM, NMOSD, and MOGAD [ 1 , 4 , 8 ]. Their exact pathogenesis remains unclear.…”

“…Based on data from cohorts and case series, first-line therapy involves high-dose corticosteroids followed by plasma exchange (PLEX) in the case of no or insufficient response, with intravenous immunoglobulins (IVIG) also being reported as a second-line therapy for some patients [ 1 , 4 , 5 , 14 , 15 ]. If first and second-line therapies fail, immunosuppressive treatment is indicated but there is no consensus on the choice and modalities of therapy [ 1 , 4 , 5 , 8 ]. In cases with underlying demyelinating conditions such as MS, NMOSD, or MOGAD, the treatment follows the standard therapy of the disease [ 5 , 14 ].…”

“…Regarding the follow-up of TDLs, the paucity of data on their natural history makes it difficult to predict their evolution to monophasic or recurrent disease. Highly heterogeneous recurrence rates have been reported in the literature, ranging from 10% to almost 70% [ 4 , 5 , 16 ].…”