Volume 11 Issue 12, December 2015

A treatment trial of the monoclonal anti-amyloid antibody solanezumab showed slight benefits in people with dementia due to mild Alzheimer disease. Drug effects on several neuropsychological testing outcomes were statistically significant, but the effect sizes were unlikely to manifest as meaningful functional benefits. Here, we discuss the implications and possible molecular underpinnings.

The molecular mechanisms of neurodegeneration due to a repeat expansion in C9orf72, the most common cause of frontotemporal dementia and amyotrophic lateral sclerosis, are unknown. Three reports now link compromised nucleocytoplasmic transport to disease pathogenesis. Whether RNA structures or dipeptide repeat proteins are most toxic in humans remains open to question.

Pneumonia impedes recovery from acute stroke and contributes to poor clinical outcomes. Two recent clinical trials demonstrate that antibiotics commonly used to treat stroke-associated pneumonia (SAP) neither reduce the frequency of pneumonia nor improve outcome after stroke when administered in a preventive manner. These findings necessitate fundamental reassessment of our current concepts of SAP.

In a new study, one-quarter of individuals with a clinical diagnosis of mild to moderate Alzheimer dementia had no or only sparse neuritic amyloid plaques in their brains, and most were also at a low or an intermediate neurofibrillary tangle stage. The findings have enormous implications for clinical trials of anti-amyloid-β and anti-tau therapies.

In our third and final installment from the MAGNIMS study group, Enzinger et al. consider how dramatic progress in MRI has enabled nonconventional structural imaging techniques to shed new light on the pathophysiology of multiple sclerosis. The authors discuss the present use of these techniques in the disease, and consider their future application to clinical research and practice.

Myoclonus is characterized by sudden, involuntary jerks, and can be caused by a variety of acquired and genetic disorders. Identification of the aetiology of myoclonus is paramount, because treatment should be based on the underlying disorder. The authors propose a novel eight-step diagnostic algorithm for myoclonus, incorporating—for the first time—next-generation sequencing. The algorithm should aid clinical decision-making and facilitate mechanism-based treatment.

Harnessing self-protective pathways in the brain could protect against neurological disease, but pharmacological attempts at such an approach have failed. In this Review, Hess et al. consider the neurological potential of remote ischaemic conditioning (RIC), a procedure in which brief ischaemia induced by vascular occlusion in the limb activates self-protective pathways and protects distant organs against longer episodes of ischaemia. Clinical trials in cardiological settings have been successful, and trials in neurological conditions suggest that RIC is a feasible option for patients with ischaemic neurological conditions.

Inflammation-driven synaptic dysfunction is emerging as a prominent pathogenic mechanism in multiple sclerosis (MS). Importantly, synaptic alterations and synaptic loss are potentially reversible, making them potential therapeutic targets. This Review draws on studies in patients with MS and in animal models of the disease to discuss the synaptic alterations in MS and the most promising drugs to restore synaptic function and intervene in the disease progression.