Kalinowska, Alicja

AbstractObjectiveIn this observational study on a cohort of biopsy‐proven central nervous system demyelinating disease consistent with MS, we examined the relationship between early‐active demyelinating lesion immunopattern (IP) with subsequent clinical course, radiographic progression, and cognitive function.MethodsSeventy‐five patients had at least one early‐active lesion on biopsy and were pathologically classified into three immunopatterns based on published criteria. The median time from biopsy at follow‐up was 11 years, median age at biopsy ‐ 41, EDSS ‐ 4.0. At last follow‐up, the median age was 50, EDSS ‐ 3.0. Clinical examination, cognitive assessment (CogState battery), and 3‐Tesla‐MRI (MPRAGE/FLAIR/T2/DIR/PSIR/DTI) were obtained.ResultsIP‐I was identified in 14/75 (19%), IP‐II was identified in 41/75 (56%), and IP‐III was identified in 18/75 (25%) patients. Patients did not differ significantly by immunopattern in clinical measures at onset or last follow‐up. The proportions of disease courses after a median of 11 years were similar across immunopatterns, relapsing–remitting being most common (63%), followed by monophasic (32%). No differences in volumetric or DTI measures were found. CogState performance was similar for most tasks. A slight yet statistically significant difference was identified for episodic memory scores, with IP‐III patients recalling one word less on average.InterpretationIn this study, immunopathological heterogeneity of early‐active MS lesions identified at biopsy does not correlate with different long‐term clinical, neuroimaging or cognitive outcomes. This could be explained by the fact that while active white matter lesions are pathological substrates for relapses, MS progression is driven by mechanisms converging across immunopatterns, regardless of pathogenic mechanisms driving the acute demyelinated plaque.

Background: Limited studies have described long-term outcomes in pathology confirmed multiple sclerosis (MS). Objectives: To describe long-term clinical–radiographic–cognitive outcomes in a prospectively followed cohort of patients with pathologically confirmed CNS demyelinating disease, consistent with MS. Methods: Subjects underwent clinical assessment, standardized 3T-MRI brain, and cognitive battery. Results: Seventy-five patients were included. Biopsied lesion size was ⩾ 2 cm in 62/75. At follow-up, median duration since biopsy was 11 years. Median EDSS was 3 and lesion burden was large (median 10 cm 3 ). At follow-up, 57/75 met MS criteria, 17/75 had clinically isolated syndrome, and 1 radiographic changes only. Disability scores were comparable to a prevalence cohort in Olmsted County ( p < 0.001, n = 218). Cognitive outcomes below age-normed standards included psychomotor, attention, working memory, and executive function domains. Total lesion volume and index lesion-related severity correlated with EDSS and cognitive performance. Volumetric cortical/subcortical GM correlated less than lesion metrics to cognitive outcomes. Conclusion: Despite early aggressive course in pathologically confirmed MS, its long-term course was comparable to typical MS in our study. Cognitive impairment in this group seemed to correlate strongest to index lesion severity and total lesion volume. It remains to be established how the aggressive nature of the lesion, biopsy, and treatment affect clinical/cognitive outcomes.

Background: Tumor necrosis factor alpha (TNF-alpha) inhibitors, such as infliximab, are commonly used to treat rheumatoid arthritis (RA) and other immune-mediated disorders. Objective: To determine whether infliximab-associated central nervous system (CNS) demyelination can be differentiated from multiple sclerosis (MS). Methods: We present a case of pathologically proven CNS demyelination in a patient treated with infliximab and describe clinical–radiographic–neuropathological findings. Putative mechanisms of TNF-alpha inhibitor-associated CNS demyelination are described. Results and conclusion: Infliximab treatment is associated with CNS inflammatory demyelinating activity, which is histopathologically indistinguishable from MS.