Clinical Correlation of Multiple Sclerosis Immunopathologic Subtypes

Abstract

Objective:To compare clinical characteristics across immunopathological subtypes of patients with multiple sclerosis.Methods:Immunopathological subtyping was performed on specimens from 547 patients with biopsy and/or autopsy confirmed CNS demyelination.Results:The frequency of immunopathological subtypes were pattern I (23%), II (56%), and III (22%). Immunopatterns were similar in terms of age at autopsy/biopsy (median age 41 years, range 4-83 years, p=0.16) and proportion female (54%, p=0.71). Median follow-up after symptom onset was 2.3 years (range 0-38y). In addition to being overrepresented among autopsy cases (45% vs. 19% in biopsy cohort, p<0.001), index attack-related disability was higher in pattern III vs. pattern II (median EDSS 4 vs. 3, p=0.02). Monophasic clinical course was more common in patients with pattern III than pattern I or II (59% vs. 33% vs. 32%, p<0.001). Similarly, patients with pattern III pathology were likely to have progressive disease compared to patients with patterns I or II, when followed for ≥5 years (24% overall, p=0.49), with no differences in long-term survival, despite a more fulminant attack presentation.Conclusion:All three immunopatterns can be detected in active lesions, although they are found less frequently later into the disease due to the lower number of active lesions. Pattern III is associated with a more fulminant initial attack than either pattern I or II. Biopsied patients appear to have similar long-term outcomes irrespective of their immunopatterns. Progressive disease is less associated with the initial immunopattern and suggests convergence into a final common pathway related to the chronically denuded axon.

Defining the architecture of cerebrospinal fluid cellular communities in neuroinflammatory diseases

“…Using this approach, we prioritized the increase in plasma cells and the reduction in microglia-like cells as more MS-specific findings, as these changes were observed in both MS vs. ONID and MS vs. IIH comparisons. Both of these findings can be interpreted in relation to MS histopathology: it is possible that the microglia-like cells are reduced in MS CSF as they are recruited to the parenchymal lesions; and given that only a subset (71%) of MS patients had higher levels of CSF plasma cells (>0.25%), the presence of plasma cells in the CSF might be associated with MS immunopattern II 37,38 , where immunoglobulin and complement deposition are observed in active lesions. Pattern II is estimated to be the most common immunopathologic pattern in MS (56%) 37 , and patients with pattern II lesions are more likely to benefit from plasma exchange 39,40 .…”

“…Both of these findings can be interpreted in relation to MS histopathology: it is possible that the microglia-like cells are reduced in MS CSF as they are recruited to the parenchymal lesions; and given that only a subset (71%) of MS patients had higher levels of CSF plasma cells (>0.25%), the presence of plasma cells in the CSF might be associated with MS immunopattern II 37,38 , where immunoglobulin and complement deposition are observed in active lesions. Pattern II is estimated to be the most common immunopathologic pattern in MS (56%) 37 , and patients with pattern II lesions are more likely to benefit from plasma exchange 39,40 . Given the observed heterogeneity in histopathology and response to treatment, future studies assessing whether CSF plasma cells can serve as a surrogate marker for pattern II MS lesions might help guide precision treatment in MS patients.…”

Tissue donations for multiple sclerosis research: current state and suggestions for improvement

“… 33 Long-term follow-up studies indicate that many of these patients will ultimately develop progressive multiple sclerosis. 54 However, it is important to closely monitor further disease evolution in presumed multiple sclerosis patients after brain biopsy. 44 , 45 …”

Ponesimod in the Treatment of Relapsing Forms of Multiple Sclerosis: An Update on the Emerging Clinical Data

“…During MS, from a pathological perspective, active tissue injury is associated with inflammation, but the inflammatory response in the progressive phase occurs at least partly trapped by the BBB, which makes it more difficult to be targeted by treatments mainly affecting neuroinflammation. 15 Other mechanisms that occur during the disease are thought to include oxidative stress resulting in mitochondrial injury that might participate in the induction of demyelination and neurodegeneration in both the RR and progressive phases of MS. 16 Thus, even though no pathological or mechanistic features are unique hallmarks in either the RR or progressive stages of MS, differences might accrual in term of quantitative rather than qualitative between these stages leading to each predominant phenotype. 15 , 16 …”

“… 15 Other mechanisms that occur during the disease are thought to include oxidative stress resulting in mitochondrial injury that might participate in the induction of demyelination and neurodegeneration in both the RR and progressive phases of MS. 16 Thus, even though no pathological or mechanistic features are unique hallmarks in either the RR or progressive stages of MS, differences might accrual in term of quantitative rather than qualitative between these stages leading to each predominant phenotype. 15 , 16 …”