Contributions
Abstract: P420
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Introduction: Neuropathological studies have demonstrated a strong association between leptomeningeal immune cell infiltration within the subarachnoid space and subpial cortical lesions, B-cell related intrathecal immunity and MS rapid disease progression. It remains still poorly understood whether the presence of perivenular immune infiltration may be similarly associated with different levels of lesion activity and disease outcome.
Aims: In order to identify the potential association between perivenular inflammation, early active white matter plaques and clinical outcome, a systematic neuropathological analysis was performed.
Methods: Using immunohistochemistry, 20 different cerebral sites from 269 post-mortem MS brains collected by the UK MS Society Tissue Bank (MSSTB) were studied. A subset had previously had detailed assessment of the presence of meningeal inflammation. The presence of early active lesions and the extent of perivenular inflammation (high/low) were examined with particular attention to the presence of the CD20+ and CD3+ cells in perivenular infiltrates.
Results: A shorter time from progression to death was associated with increased prevalence of early active lesions and high levels of perivenular inflammation (both p< .0001) in the SPMS cases examined. Independently, earlier age of onset and shorter time from onset to progression further increased the prevalence of these features. A shorter time from onset of progression to wheelchair use was associated with a higher prevalence of early active lesions (OR 0.921, 95% CI (0.858, 0.989), p=0.0230) and a higher level of perivenular inflammation (OR 0.932, 95% CI (0.886, 0.981), p=0.0071). Early active lesions were present in 35% (48/136) of cases with high levels of perivenular inflammation, but were less frequent (11/127) in the absence of perivenular inflammation. Elevated levels of meningeal inflammation were associated with a high degree of perivenular inflammation (29/34) and significantly higher levels of B cells within perivenular infiltrates.
Conclusions: The association of early active lesions and high levels of perivenular inflammation with a rapid progressive phase and higher levels of both meningeal and perivascular B-cell infiltrates is consistent with the hypothesis that chronic inflammation drives the progressive MS phase in some way. Predicting their presence in the progressive phase before a wheelchair is required will help to extend the window of therapeutic opportunity.
Disclosure:
Magliozzi R.: Nothing to disclose
Roncaroli F.: Nothing to disclose
Muraro P.: Nothing to disclose
Howell O.: Nothing to disclose
Reynolds R.: Nothing to disclose
Friede T.: Nothing to disclose
Nicholas R.: Nothing to disclose
Abstract: P420
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Introduction: Neuropathological studies have demonstrated a strong association between leptomeningeal immune cell infiltration within the subarachnoid space and subpial cortical lesions, B-cell related intrathecal immunity and MS rapid disease progression. It remains still poorly understood whether the presence of perivenular immune infiltration may be similarly associated with different levels of lesion activity and disease outcome.
Aims: In order to identify the potential association between perivenular inflammation, early active white matter plaques and clinical outcome, a systematic neuropathological analysis was performed.
Methods: Using immunohistochemistry, 20 different cerebral sites from 269 post-mortem MS brains collected by the UK MS Society Tissue Bank (MSSTB) were studied. A subset had previously had detailed assessment of the presence of meningeal inflammation. The presence of early active lesions and the extent of perivenular inflammation (high/low) were examined with particular attention to the presence of the CD20+ and CD3+ cells in perivenular infiltrates.
Results: A shorter time from progression to death was associated with increased prevalence of early active lesions and high levels of perivenular inflammation (both p< .0001) in the SPMS cases examined. Independently, earlier age of onset and shorter time from onset to progression further increased the prevalence of these features. A shorter time from onset of progression to wheelchair use was associated with a higher prevalence of early active lesions (OR 0.921, 95% CI (0.858, 0.989), p=0.0230) and a higher level of perivenular inflammation (OR 0.932, 95% CI (0.886, 0.981), p=0.0071). Early active lesions were present in 35% (48/136) of cases with high levels of perivenular inflammation, but were less frequent (11/127) in the absence of perivenular inflammation. Elevated levels of meningeal inflammation were associated with a high degree of perivenular inflammation (29/34) and significantly higher levels of B cells within perivenular infiltrates.
Conclusions: The association of early active lesions and high levels of perivenular inflammation with a rapid progressive phase and higher levels of both meningeal and perivascular B-cell infiltrates is consistent with the hypothesis that chronic inflammation drives the progressive MS phase in some way. Predicting their presence in the progressive phase before a wheelchair is required will help to extend the window of therapeutic opportunity.
Disclosure:
Magliozzi R.: Nothing to disclose
Roncaroli F.: Nothing to disclose
Muraro P.: Nothing to disclose
Howell O.: Nothing to disclose
Reynolds R.: Nothing to disclose
Friede T.: Nothing to disclose
Nicholas R.: Nothing to disclose