CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study.

OBJECTIVE: To study long-term outcomes in patients with CNS demyelinating events exposed to TNFa-inhibitors (TNFai), including subsequent clinical relapse, MRI lesions, and use of disease modifying therapy (DMT) for MS. METHODS: Adult patients evaluated for a CNS demyelinating disease during TNFai use were identified at Mass General Brigham [01/1998-08/2020] and analyzed in clinically-relevant subgroups. Inclusion criteria required a first neurological event while taking a TNFai, MRI lesions consistent with demyelination, and the absence of a more probable alternative diagnosis. RESULTS: 21 cases (mean age 44 years, 20 female, 14 ≥ 2 MS risk factors) had an index neurological event (INE) at a median of 12 months (range 1-176) from onset of TNFai use (adalimumab in 10, etanercept 6, infliximab 5). MRI lesions were most often present in periventricular (16/20, 80%) and spinal zones (10/20, 50%); 37% (7/19) met ≥ 2 Barkhof criteria at onset. CSF testing was abnormal in 64% (7/11). 67% (10/15) with available follow-up MRIs developed new lesions by a median of 29.5 months of MRI surveillance (median MRI surveillance 60 months); 55% (11/20) met ≥ 2 Barkhof criteria. 47% (8/17) suffered a clinical relapse by a median of 40.5 months of clinic follow-up (median clinic follow-up since INE: 26 months). In patients discontinuing TNFai (18/21, 86%) at INE onset, 56% (10/18) had further evidence of CNS demyelination. Six patients (6/21, 29%) started an MS disease modifying therapy (DMT) at INE of whom 50% (3/6) had subsequent disease activity. Continuing or restarting TNFai was followed by relapse in 75% (3/4). 65% (13/20) met 2017 McDonald criteria for MS at INE with another 10% (15/20, 75%) by study conclusion. CONCLUSIONS: With extended follow-up, a majority of patients had a relapsing CNS demyelinating disorder-as evidenced by new MRI lesions or clinical relapses-despite TNFai discontinuation.

Differential diagnosis of multiple sclerosis and other inflammatory CNS diseases.

Multiple sclerosis (MS) is the most common acquired demyelinating disorder of the central nervous system (CNS). Diagnosing MS can be very challenging owing to its variable clinical features and lack of specific tests. Magnetic resonance imaging (MRI) is a key measure in this process. Although white matter lesions on brain MRI are regarded as a hallmark of MS, they are a common radiological finding and their pattern may overlap in particular CNS inflammatory diseases. The increasing availability of therapies for MS and the knowledge of benefits associated with an early treatment underscore the importance of precise and quick diagnosis. Despite an extensive research, currently no fully specific diagnostic test is available to distinguish between CNS inflammatory disorders. In this review, we discuss characteristic findings and distinctive features of CNS inflammatory disorders, with particular focus on rheumatic diseases.