Contributions
Abstract: 2
Type: Hot Topic
Abstract Category: N/A
The rate of physical and cognitive disability progression in multiple sclerosis (MS), both in the relapsing and progressive phases, has been demonstrated to be strictly associated with degenerative cerebral grey matter (GM) pathology. The exact involvement/load and the specific inflammatory features of GM damage in MS remain still not fully understood. Moreover, the radiological aspects of cortical demyelination and inflammation are still poorly characterized due to the lack of imaging tools available to reliably assess all the heterogeneous aspects of cortical MS pathology.
Recent neuropathological findings reported that high levels of inflammatory infiltration, diffuse and/or structured in tertiary lymphoid organ-like (TLO), in the meninges of a subgroup of MS patients positively correlate with extensive, active subpial GM damage and more rapid and severe clinical progression. Cortical injury associated with meningeal infiltrates occurs through a gradient “surface-in” of neuronal, astrocyte and oligodendrocyte loss and microglia activation, elevated close to the pial surface and decreasing towards the inner cortical layers and white matter.
Since meningeal infiltrates, together with circulating cells in the subarachnoid space, have been suggested as one the major contributors in releasing inflammatory/cytotoxic mediators in the cerebrospinal fluid (CSF), it is reasonable to hypothesize that intrathecal (meninges and CSF) inflammation, chronically compartmentalized within the central nervous system (CNS), might have a key role in mediating cortical damage and rapid progressive evolution of the disease.
Lately, combined neuropathology, CSF and MRI analysis has demonstrated that a specific CSF inflammatory profile, including high protein levels of CXCL13, IFNγ, TNF, CXCL12, IL6, IL10 and LIGHT, is indeed able to predict up to 89% of the variance in GM number/volume in a subgroup of either in vivo MS patients at time of diagnosis or in post-mortem MS populations with increased meningeal inflammation.
A specific CSF inflammatory pattern might represent a useful surrogate marker of meningeal inflammation able to early identify MS patients with more severe GM demyelination and higher risk of disease progression.
Disclosure: R. Magliozzi: nothing to disclose
Abstract: 2
Type: Hot Topic
Abstract Category: N/A
The rate of physical and cognitive disability progression in multiple sclerosis (MS), both in the relapsing and progressive phases, has been demonstrated to be strictly associated with degenerative cerebral grey matter (GM) pathology. The exact involvement/load and the specific inflammatory features of GM damage in MS remain still not fully understood. Moreover, the radiological aspects of cortical demyelination and inflammation are still poorly characterized due to the lack of imaging tools available to reliably assess all the heterogeneous aspects of cortical MS pathology.
Recent neuropathological findings reported that high levels of inflammatory infiltration, diffuse and/or structured in tertiary lymphoid organ-like (TLO), in the meninges of a subgroup of MS patients positively correlate with extensive, active subpial GM damage and more rapid and severe clinical progression. Cortical injury associated with meningeal infiltrates occurs through a gradient “surface-in” of neuronal, astrocyte and oligodendrocyte loss and microglia activation, elevated close to the pial surface and decreasing towards the inner cortical layers and white matter.
Since meningeal infiltrates, together with circulating cells in the subarachnoid space, have been suggested as one the major contributors in releasing inflammatory/cytotoxic mediators in the cerebrospinal fluid (CSF), it is reasonable to hypothesize that intrathecal (meninges and CSF) inflammation, chronically compartmentalized within the central nervous system (CNS), might have a key role in mediating cortical damage and rapid progressive evolution of the disease.
Lately, combined neuropathology, CSF and MRI analysis has demonstrated that a specific CSF inflammatory profile, including high protein levels of CXCL13, IFNγ, TNF, CXCL12, IL6, IL10 and LIGHT, is indeed able to predict up to 89% of the variance in GM number/volume in a subgroup of either in vivo MS patients at time of diagnosis or in post-mortem MS populations with increased meningeal inflammation.
A specific CSF inflammatory pattern might represent a useful surrogate marker of meningeal inflammation able to early identify MS patients with more severe GM demyelination and higher risk of disease progression.
Disclosure: R. Magliozzi: nothing to disclose