A Review of Compartmentalised Inflammation and Tertiary Lymphoid Structures in the Pathophysiology of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system (CNS). The most common form of MS is a relapsing–remitting disease characterised by acute episodes of demyelination associated with the breakdown of the blood–brain barrier (BBB). In the relapsing–remitting phase there is often relative recovery (remission) from relapses characterised clinically by complete or partial resolution of neurological symptoms. In the later and progressive stages of the disease process, accrual of neurological disability occurs in a pathological process independent of acute episodes of demyelination and is accompanied by a trapped or compartmentalised inflammatory response, most notable in the connective tissue spaces of the vasculature and leptomeninges occurring behind an intact BBB. This review focuses on compartmentalised inflammation in MS and in particular, what we know about meningeal tertiary lymphoid structures (TLS; also called B cell follicles) which are organised clusters of immune cells, associated with more severe and progressive forms of MS. Meningeal inflammation and TLS could represent an important fluid or imaging marker of disease activity, whose therapeutic abrogation might be necessary to stop the most severe outcomes of disease.