News & Views in 2015

The recent DOMINO-AD trial suggests that continued treatment with donepezil delays nursing home placement for patients with severe Alzheimer disease, but more work is needed to support strong conclusions about whether the benefits outweigh the costs.

Parkinson disease (PD) is now regarded as a mixed motor, nonmotor and multiorgan disorder rather than a pure movement disorder. Nonmotor symptoms (NMS) have underpinned this conceptual change, and new criteria for clinical and prodromal diagnosis of PD, incorporating a range of NMS, have recently been published.

In Europe, use of intravenous tissue plasminogen activator (tPA) in patients older than 80 years is discouraged because these patients have been excluded from certain past clinical trials. A new retrospective, observational study shows that tPA can substantially improve functional outcome after ischaemic stroke in patients aged 80–89 years.

Whole-exome sequencing is a new tool for neuromuscular clinicians, and recent findings show that it improves the diagnosis of limb-girdle muscular dystrophy. The technique has a dual role as a tool for diagnosis and discovery in genetically heterogeneous neuromuscular diseases.

A randomized, double-blind, phase III trial of generic glatiramer acetate has shown equivalent efficacy and safety compared with the approved formulation, Copaxone. The impact of approval of generic glatiramer acetate, however, will mainly depend on the pricing of the drug.

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.

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.

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.

The past decade of multiple sclerosis research has been marked by important advances in understanding the disease, a dramatic increase in the range of treatment options and a new spirit of data sharing in research for patient benefit. This progress has made personalized medicine in multiple sclerosis a realistic possibility.

CNS infections have severe manifestations, often leading to high mortality, but the CNS is usually not the primary target of pathogens, leaving a window of opportunity to prevent neuroinvasion. We must prioritize development of therapies to prevent neurological sequelae that cause long-lasting morbidity and disease burden on society.

Since 2005, we have made substantial progress in understanding the pathophysiology and natural history of movement disorders such as Parkinson disease and Huntington disease. However, disease-modifying therapies for these conditions have proved elusive and, as a consequence, treatments remain largely symptomatic.

In the past 10 years, the realization that migraine is a brain disorder rather than a vascular disorder has facilitated development of various treatments, ranging from innovative immunopharmaceuticals through to neurostimulation. Many clinical trials have been successful, and such considerable progress holds promise for the coming decade of migraine treatment.

Recent decades have seen a dramatic reduction in age-adjusted stroke-related mortality, presumably owing to better control of vascular risk factors, use of antithrombotic agents and improvements in acute stroke care. Here, we highlight a few developments in stroke prevention and acute care that have particularly influenced the care of patients.

The past decade has yielded a host of important conceptual advances in epilepsy, along with some promising findings related to diagnostics and therapeutics. We are on an upswing where precise identification of the cause of a patient's seizure disorder can be matched to therapy that has a high likelihood of success.

In my personal view, the past decade in dementia research has been marked by remarkable discoveries in the field of frontotemporal dementia, accompanied by steady scientific consolidation tinged with therapeutic disappointments related to Alzheimer disease.

A large study from the USA suggests that epilepsy in pregnant women elevates the risk of adverse events both to the mother and the fetus, including an 11-fold increase in the risk of death of the mother at delivery. Although the data are intriguing, the study has caveats that call for cautious interpretation.

A new study describes a biomarker profile based on cerebrospinal fluid (CSF) tau and amyloid-β_1–42 in a uniquely large population with a variety of dementia diagnoses. This study confirms the differential diagnostic value of CSF biomarkers and further highlights the important neuropathological overlap between dementia aetiologies.

The ABCD2 score was developed to triage patients with transient ischaemic attack according to the risk of experiencing a stroke in the next few hours or days. However, a new systematic review and meta-analysis on the ABCD2 score gives us considerable cause to rethink its value for clinical situations.

The results of a futility trial, which used the PPAR-γ receptor agonist pioglitazone in an attempt to modify disease progression in Parkinson disease, do not support initiation of further trials. However, although this trial was well designed and conducted, we question whether it is time to fully shut the door on pioglitazone.