Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

  title={Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis},
  author={Edgar Meinl and Markus Krumbholz and Tobias Derfuss and Andreas Junker and Reinhard Hohlfeld},
  journal={Journal of the Neurological Sciences},
Intrathecal immune reset in multiple sclerosis: exploring a new concept.
The neuropathological basis of clinical progression in multiple sclerosis
The contributions that the various types of pathology are likely to make to the increasing neurological deficit in MS are reviewed.
Role of B cells and antibodies in multiple sclerosis.
Multiple sclerosis animal models: a clinical and histopathological perspective
To what extent pathology of the progressive disease stage can be modeled in MS animal models is discussed, and which pathological aspects of the disease can be best studied in the various animal models available is discussed.
Past, Present and Future of Cell-Based Therapy in Progressive Multiple Sclerosis
Major expectation arises from the use of oligodendrocyte progenitor cells for directly replacing the damaged myelin and non-haematopoietic stem cells for the potential of influencing host immune response and endogenous mechanisms of repair.
Intense Inflammation and Nerve Damage in Early Multiple Sclerosis Subsides at Older Age: A Reflection by Cerebrospinal Fluid Biomarkers
A strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients is demonstrated and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later disease stages.
The relation between inflammation and neurodegeneration in multiple sclerosis brains
It is found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease, and the disease processes of multiple sclerosis may die out in aged patients with long-standing disease.
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis.
The findings suggest that meningeal infiltrates may play a contributory role in the underlying subpial grey matter pathology and accelerated clinical course, which is exacerbated in a significant proportion of cases by the presence of B cell follicle-like structures.
Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials.
The recent evidence supporting the need for trials based on the intrathecal use of rituximab in multiple sclerosis is summarized.


Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology.
Data support an immunopathogenetic mechanism whereby B-cell follicles developing in the multiple sclerosis meninges exacerbate the detrimental effects of humoral immunity with a subsequent major impact on the integrity of the cortical structures.
B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production, and therapeutic modulation
These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands and outline the possibly double‐edged effects of B cells and immunoglobulin in the CNS.
Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis.
This study suggests that a compartmentalized B cell response occurs within the CNS during an ongoing inflammatory reaction, through a recapitulation of all stages of B cell differentiation observed in secondary lymphoid organs.
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain
Findings from this study are interpreted as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.
Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis
Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum
Multiple sclerosis: T-cell receptor expression in distinct brain regions.
P pervasive T-cell clones exist in distinct regions of MS brain, and these clones are 'private' (unique) to individual patients, supporting the pathogenic relevance of this T- cell subset.
Cortical demyelination and diffuse white matter injury in multiple sclerosis.
Global brain pathology in multiple sclerosis is analysed, focusing on the normal-appearing white matter (NAWM) and the cortex, to suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter.
Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis
A serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis treated with methylprednisolone and 26 patients treated with placebo in two randomized controlled trials is reported, suggesting differential involvement of CX CL10 andCCL2 in CNS inflammation.
Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment.
The strong linkage of CXCL13 to immune cells and immunoglobulin levels in CSF suggests that this is one of the factors that attract and maintain B and T cells in inflamed CNS lesions.