Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials.

Depression, migraine with aura and migraine without aura: their familiality and interrelatedness.

Migraine is frequently comorbid with depression. There appear to be common aetiological factors for both disorders, but the aetiology of migraine within depressed patients, in particular the significance of aura, has been little studied. A large sample of concordantly depressed sibling pairs [the Depression-Network (DeNT) sample] was assessed as having migraine with aura (MA), migraine without aura (MoA), probable migraine or no migraine according to International Headache Society guidelines. Correlations between siblings' migraine status were used to assess the nature of familial liability to migraine. A multiple threshold isocorrelational model fit best, in which different syndromes are conceptualized as different severities of one underlying dimension rather than as having separate aetiologies. Thus, MA and MoA were found to be different forms of the same disorder, with MA occupying the more extreme end of the spectrum of liability. Implications for our understanding of the relationship between migraine and depression are discussed.