Volume 8 Issue 11, November 2012

Multiple sclerosis is an inflammatory, demyelinating disease in which antigens of the myelin sheath have been considered the autoimmune target. A recent study suggests that the potassium channel KIR4.1 is another potential autoantigen in some patients with multiple sclerosis, and might also be a target in other demyelinating diseases.

Natural history of multiple sclerosis includes phases of relapse, remission and insidious progression. New data show that sustained improvements in disease, defined by reductions in EDSS scores, occur independent of relapses almost half as frequently as disease worsening. This finding might facilitate research into the biological processes involved in disease improvement.

Whether dominantly inherited variants of Alzheimer disease (AD) and 'sporadic' forms exhibit similar pathophysiological and biomarker signatures remains unresolved. A landmark study has proposed a biomarker progression model of dominantly inherited AD, but a complex systems biology and physiology approach is required to translate these findings to sporadic disease.

In a recent trial investigating the effectiveness of speech and language therapy versus a control intervention in poststroke aphasia, patient outcome improved equally in both groups. However, flaws in the study relating to design of the control intervention, inadequate therapy 'dose', and the interpretation of null results should be highlighted.

Strong evidence supports the importance of genetic factors in the development of multiple sclerosis (MS), but environmental factors also have a major role. Ascherio et al. review the evidence for such factors, with a focus on three main aspects: infection with Epstein–Barr virus, vitamin D nutrition, and cigarette smoking. They discuss how these processes might influence the initiation of MS, the potential for therapeutic approaches that target these risk factors, and how lifestyle modification could aid in MS prevention.

Increasing evidence supports a role for B cells and antibodies in the pathogenesis of multiple sclerosis (MS). Here, Meinl and colleagues discuss the proinflammatory contribution of B-cell signalling in MS, and consider potential targets of autoantibodies. The B-cell response to various MS therapies is also summarized.

In recent years, the central roles of neuronal and axonal damage, as well as axon–glial and axon–myelin interactions, in the pathogenesis and progression of multiple sclerosis (MS) have become increasingly apparent. Franklin et al. review advances in our understanding of the molecular mechanisms underlying these MS-related events, and discuss approaches towards axonal neuroprotection and repair, particularly through the regenerative process remyelination.

Despite widespread damage associated with multiple sclerosis (MS) pathology, recovery of function can occur, driven by adaptive plasticity in brain networks. Tomassini et al. review the mechanisms underlying functional recovery in MS, and discuss interventions that might promote this process. Methodological considerations for imaging neuroplasticity using functional MRI are also highlighted.

Over the past few decades, considerable progress has been made in understanding the mechanisms underlying the relapsing–remitting stage of multiple sclerosis (MS), but the disease processes that drive progressive MS remain largely unresolved. In this Review, Lassmann and colleagues explore the current state of knowledge on the pathophysiology of progressive MS, and present a pathogenetic concept for this phase of the disease that involves oxidative stress and mitochondrial injury.

Multiple sclerosis (MS) is an inflammatory, demyelinating neurological disease that causes severe disability. Current treatments are only partially effective, and No. cure is available. This issue of the journal focuses on disease mechanisms that operate in different phases in MS—including initiation, exacerbation, remyelination and functional recovery, and progression—placing the latest findings in a clinical context, including implications for therapy.