News & Views in 2019

Two new studies show that gliomas can manipulate normal elements of neuronal development and plasticity to create neuron–glia synapses, activation of which leads to glioma proliferation. Interventions that target the AMPA receptor could slow down tumour growth by altering this synaptic transmission.

Artificial intelligence algorithms are well suited to the fast decision making needed in the management of large vessel occlusive stroke. In a new study, a fully automated CT angiography algorithm identified large vessel occlusions with impressive sensitivity, but the work highlights the need for high reporting standards to maximize translatability.

A new study provides direct biological evidence for a prodromal phase of multiple sclerosis (MS), with implications for studying disease aetiology and underscoring the limitations of therapies that solely target inflammation. The findings also suggest an opportunity to apply secondary prevention strategies at the very earliest stages of the disease.

A new study shows that the monoclonal antibody fremanezumab is effective for migraine prophylaxis, even in patients who have failed to respond to multiple preventive treatments. However, not all patients benefit from this treatment, and detailed investigation of non-responders could help to identify additional pharmacological targets and increase the number of responders.

A new study — unique in its size, scope and collaborative nature — has identified genetic variants that are associated with progression of Parkinson disease (PD). However, limitations of the study highlight the need for large-scale, phenotype-harmonized, multi-ethnic, longitudinal studies to characterize PD subtypes and develop individualized therapies.

Outdated knowledge of arterial perfusion territories still guides clinical decisions and management in acute and chronic stroke. In a new study, application of machine learning techniques provides more detail than ever before, laying the foundation for improved stroke management and new research.

Understanding the heterogeneity of typical Alzheimer disease (AD) is of increasing importance for the development of new and effective treatments. A new study in patients with AD described two robust cognitive subtypes with different pathology distributions, genetic backgrounds and clinical trajectories.

The benefits of targeting calcitonin gene-related peptide (CGRP) could go beyond migraine prevention, and three new studies report success with a new small-molecule CGRP receptor antagonist in acute migraine and with a monoclonal antibody in cluster headache.

Guillain–Barré syndrome (GBS) outbreaks associated with endemic and epidemic infections have increased in recent decades, and the need for standard treatment guidelines is compelling. A new study presents data from a worldwide prospective observational registry, providing insights into current treatment practices and laying the foundations for future clinical trials.

A new report presents post-mortem neuropathological follow-up of patients 4 months to 15 years after they received active amyloid-β (Aβ) immunization during its first trial in Alzheimer disease. The study documents effects on plaque clearance, tau pathology, plasma anti-Aβ antibody titres and final cognitive status; variability was seen between patients.

A new study has found that levels of primary fatty amides in plasma correlate with amyloid-β pathology and other Alzheimer disease (AD)-related phenomena. In addition to identifying potential plasma biomarkers for AD, the findings suggest new avenues for investigation into the early stages of AD.

A new trial has demonstrated the benefits of intravenous thrombolysis, guided by perfusion imaging, 4.5–9.0 h after stroke onset and in individuals with wake-up stroke. In addition to extending the time window for thrombolysis after acute ischaemic stroke, these findings could aid the refinement of imaging and thrombolytic protocols.

The Global Burden of Disease, Injuries and Risk Factors 2016 study has shown that neurological diseases have the highest burden and that this burden is increasing. Stroke is the biggest contributor, highlighting a need to improve resources globally for stroke prevention, management and rehabilitation.

Patients present to general practitioners with a variety of symptoms that eventually turn out to be caused by early Parkinson disease. Now, methods to calculate Parkinson disease risk in general practitioner settings are becoming available.

A new study has demonstrated recovery of brain circulation and some cellular function in a decapitated pig model. Although these results are exciting and thought-provoking, they do not challenge the concept or practical implications of brain death, as no evidence of global electrical activity or functional recovery of the brain was presented.

A new study suggests that patients with relapsing–remitting multiple sclerosis can experience long-term increases in disability in the absence of disease relapses. Monitoring this ‘silent progression’ will require a paradigm shift in the way disease progression is evaluated.

In a new study of 1,102 patients, a multi-item prognostic tool has been developed and validated for use in acute stroke. Using a mix of clinical variables (age and stroke severity), a process variable (administration of thrombolysis) and a biomarker (plasma copeptin), the authors were able to predict 3-month disability.

Previous open-label trials testing glial cell line-derived neurotrophic factor (GDNF) family ligands in Parkinson disease have shown promising clinical effects. However, in placebo-controlled trials, the treatments have failed. A new randomized placebo-controlled trial of intraputamenal delivery of GDNF designed to resolve this conundrum has again failed to do just that.

Studies in melanoma and lung cancer indicate that shifting use of immune checkpoint inhibition from palliative stages to the neoadjuvant setting improves response rates and patient outcomes. Three studies now show that neoadjuvant programmed cell death 1 (PD1) inhibition modulates the immune tumour microenvironment — but does this effect translate into a real patient benefit?

A new study has identified novel genes involved in sporadic frontotemporal lobar degeneration with neuronal inclusions of TAR DNA-binding protein 43. These findings might enable the elucidation of pathogenic mechanisms of the disease and have implications for the identification of potential therapeutic targets.