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Published on: April 14, 2014
Long-term clinical, imaging and cognitive outcomes association with MS immunopathology
Alicja Kalinowska-Lyszczarz1,2, Jan-Mendelt Tillema1, William Oliver Tobin1
1Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Objective:
In 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.
Methods:
Seventy-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.
Results:
IP-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.
Interpretation:
In 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.
Insights
Early active lesions in multiple sclerosis (MS) show diverse immunopathology but do not predict long-term clinical, imaging, or cognitive outcomes. MS progression appears driven by common mechanisms irrespective of initial lesion immunopattern.
Area of Science:
- Neurology
- Immunopathology
- Neuroimaging
Background:
- Multiple sclerosis (MS) is a central nervous system demyelinating disease characterized by inflammatory lesions.
- The immunopathological classification of early-active demyelinating lesions may offer insights into disease heterogeneity.
Purpose of the Study:
- To investigate the relationship between early-active demyelinating lesion immunopattern (IP) and the long-term clinical course, radiographic progression, and cognitive function in MS patients.
- To determine if distinct lesion immunopatterns correlate with different long-term outcomes in biopsy-proven MS.
Main Methods:
- Observational study of 75 patients with biopsy-proven MS and early-active lesions.
- Lesions were classified into three immunopatterns (IP-I, IP-II, IP-III).
- Long-term follow-up (median 11 years) included clinical assessments (EDSS), cognitive testing (CogState), and 3-Tesla MRI.
Main Results:
- Immunopatterns were identified as IP-I (19%), IP-II (56%), and IP-III (25%).
- No significant differences were observed in clinical measures, disease course proportions, volumetric MRI, DTI measures, or most cognitive tasks across immunopatterns.
- A minor, statistically significant deficit in episodic memory was noted in IP-III patients.
Conclusions:
- The immunopathological heterogeneity of early-active MS lesions at biopsy does not correlate with divergent long-term clinical, neuroimaging, or cognitive outcomes.
- MS progression may involve convergent pathogenic mechanisms that override initial lesion immunopattern differences.
