Reviews & Analysis

A recent study demonstrates that amyloid-β (Aβ) can function as an antimicrobial peptide, and additional data show that bacteria and yeast can seed Aβ deposition into amyloid. These data suggest a complex interplay between the normal function of Aβ, its accumulation in the brain, and host immune defence.

The Glasgow Outcome Scale (GOS) is widely recommended as an outcome measure after traumatic brain injury. Following the 40^thanniversary of its original publication, McMillan and colleagues review the development of the GOS and its extension and refinement over the past four decades, and consider how it can contribute to further understanding of brain injury.

A new meta-analysis, which evaluated individual patient data from randomized trials of aspirin in patients with non-disabling acute brain ischaemia, found this drug to be much more efficacious at reducing early stroke recurrence than was previously estimated.

About 2% of the general population and 8% of people with migraine have chronic migraine, defined as ≥15 headache days per month. The condition can be disabling and has a severe impact on quality of life, yet it receives little attention. This Review summarizes the current understanding of the risk factors and pathophysiological mechanisms of migraine chronification, and discusses strategies to prevent and treat the disorder.

Participants in collision sports show a high incidence of concussion and can have deleterious long-term consequences for brain function. Here, Rebekah Mannix and colleagues discuss the benefits and risks associated with the practice of contact sports and examine how this balance affects policies regarding the practice of collision sports.

The archetypal vascular endothelial growth factor, VEGF, arose in evolution as a signal affecting neural cells, and was subsequently co-opted to regulate vascular function. Here, the authors review the roles of the VEGF family as both aetiological factors and therapeutic targets in neurological disease.

Alteplase is widely used for acute stroke at a dose of 0.6 mg/kg in Asian patients, whereas the standard in Europe and the USA is 0.9 mg/kg. The ENCHANTED study did not show that 0.6 mg/kg alteplase is noninferior to 0.9 mg/kg, as previously suggested, raising questions about standard practice in Asia.

Overactivation of the mechanistic target of rapamycin (mTOR) signalling pathway contributes to neurological disorders, including neurodevelopmental disorders, tuberous sclerosis complex, epilepsy, and tumours of the CNS. In this Review, Peter Crino discusses the pathophysiological role of mTOR in neurological diseases and provides an overview of clinical trials that have assessed the efficacy of mTOR inhibitors in these diseases.

Premutation CGG expansions in theFMR1gene can lead to various premutation disorders throughout life and ultimately lead to fragile X-associated tremor/ataxia syndrome (FXTAS) in late life. In this Review, the authors summarize our current understanding of the clinical features and management of FXTAS, and consider how our advancing understanding of the pathogenic mechanisms could lead to new therapies.

The American Academy of Neurology (AAN) has updated its guidelines on the use of botulinum neurotoxins in neurological disorders. The new guidelines provide individual recommendations for the four products that are commercially available in the USA; however, the clinical differences between the products are still not clear.

The Response Assessment in Neuro-Oncology Working Group has analysed the role of clinically established PET methods in the diagnostic assessment of brain tumours. The group emphasizes the clinical value of PET imaging, particularly amino acid PET imaging, over conventional MRI, and recommends its use at every stage of management.

Numerous genetic variants have been associated with late-onset Alzheimer disease (LOAD) but the determination of their effect has proven challenging. Here, Gaiteri and co-workers discuss how the analysis of molecular and brain networks and their combination into multiscale models can provide a more comprehensive and clinically relevant representation of the effects of LOAD-associated genetic variants

Skeletal muscle disorders of glycogenolysis and glycolysis account for most of the conditions collectively termed glycogen storage diseases. Godfrey and Quinlivan outline the distinguishing features of these disorders, and they describe a large European registry, EUROMAC, that has been established to pool and transfer knowledge regarding McArdle disease and other rare disorders of carbohydrate metabolism.

In modern X-ray therapy, healthy brain tissue that surrounds a CNS tumour receives low to medium dose irradiation, which has important long-term adverse effects such as cognitive toxicity, endocrinopathy, hearing loss and vasculopathic effects. Prolonged long-term survival in certain paediatric CNS tumours call for more attention in avoiding the long-term sequelae of radiotherapy. This Review discusses how proton therapy improves dose distribution and can help reduce long-term toxicities.

Extracellular vesicles (EVs) are released by most cell types, and they carry a cargo of protein and nucleic acid that reflects the cell of origin. Thompson and colleagues review current knowledge of the biology and function of EVs, including evidence for their involvement in neurodegenerative disease pathogenesis, and their potential as CNS-specific biomarkers.

Diagnosis of Creutzfeldt–Jakob disease (CJD) in living patients is challenging, but distinguishing this untreatable disease from treatable rapidly progressive dementias is essential, and will also help prevent iatrogenic transmission of CJD. In this Review, Zanusso et al. discuss novel techniques, such as ultrasensitive protein seeding assays and nasal brushings, that can aid antemortem diagnosis of CJD.

The ongoing Zika virus (ZIKV) epidemic in the Americas raises urgent questions about the risks of microcephaly in the children of ZIKV-infected mothers. New research into the 2013–2014 ZIKV outbreak in French Polynesia supports a link between maternal ZIKV infection during the first trimester of pregnancy and microcephaly.

Two new studies report on the potential of a number of antioxidants and a cholesterol-lowering drug to prevent neurodegeneration in a Drosophila genetic model of parkinsonism. This research shines a spotlight on the power of invertebrate models as an in vivo screening tool.

MRI-based visualization of demyelinated CNS lesions is pivotal to the diagnosis and monitoring of multiple sclerosis (MS). The authors describe how advanced multimodal neuroimaging techniques are providing valuable insights into lesion structure and blood–brain barrier dynamics, thereby narrowing the gap between the macroscopic view of the radiologist and the microscopic view of the pathologist. The findings in humans are compared with data from a primate model of MS — experimental autoimmune encephalomyelitis in the common marmoset.

A new study reports that the incidence of dementia in one population has declined by over 40% between the 1970s and 2010s. The finding could have implications for the future prevalence of dementia, and illustrates the importance of environmental factors in the risk of dementia disorders.