News & Views in 2021

Rare neurological complications can occur after COVID-19 vaccination, but recent studies show that such complications are much more common after SARS-CoV-2 infection. Novel approaches to risk–benefit analysis such as Bayesian network models can integrate the latest global evidence with local factors to inform decision-making and support the global vaccination effort.

A recent clinical trial found no effect of chronic intranasal oxytocin on social behaviour in children with autism spectrum disorders. The result is not surprising, as oxytocin facilitates social learning but does not directly cause prosocial behaviour. In future trials, oxytocin should be paired with behavioural therapy to enhance learning and improve social behaviour.

A new study found methylphenidate to be effective in treating apathy in individuals with Alzheimer disease. At a time when the recent aducanumab approval is focusing attention on the promise of disease-modifying therapies, the new findings highlight the importance of developing better symptomatic treatment options for individuals with psychiatric disorders of Alzheimer disease.

The neurological deficits caused by COVID-19, which were first reported in the early months of 2020, continue to intrigue neurologists and health-care professionals worldwide. As two new studies highlight, these manifestations are frequent and are expected to increase the burden of morbidity and mortality in the acute and chronic phases of COVID-19.

Detailed immunological analysis in a new study provides insight into the mechanisms of immune responses after SARS-CoV-2 vaccination in people who are receiving B cell-depleting therapy for multiple sclerosis. The findings have implications for clinical practice, but more questions about SARS-CoV-2 vaccination and immunosuppression remain.

Two-thirds of patients with Alzheimer disease (AD) are women, and sex differences in AD pathology have been observed, yet little is known about the role of sex chromosomes in AD. New research suggests that X-linked gene expression modifies AD risk in a sex-specific manner. This knowledge could aid the development of precision medicine approaches for AD.

Results of a new study have shown the enormous potential of smartphone-collected, real-world data for the differentiation of patients with Parkinson disease from controls. This study spearheads a new phase for the evaluation of symptoms associated with Parkinson disease that is patient-centred, digital, objective, continuous and relevant to everyday life.

More than 90% of people with Down syndrome develop Alzheimer disease but receive little or no treatment for their dementia. Novel biomarkers of ageing and dementia bring new hope to this medically vulnerable population and can also help researchers understand dementia in other populations.

A randomized, placebo-controlled trial has found the neonatal Fc receptor modulator efgartigimod to be an effective therapy for generalized myasthenia gravis. If a pending FDA application is approved, the treatment will be the first recombinant antibody-based therapy for selective IgG depletion, adding to a growing spectrum of treatment options for myasthenia gravis.

During Parkinson disease progression, the accumulation of α-synuclein pathology is paralleled by changes in structural and functional connectivity in the brain. Two new studies pinpoint specific alterations in the brain connectome in the early stages of Parkinson disease and suggest future avenues of research to develop connectome-based biomarkers.

Results of a new study have identified an association between risk of incident Parkinson disease and exposure to NO₂, which is released into the atmosphere as a result of burning fuels. Parkinson disease has a long prodromal phase, so these findings suggest an opportunity to apply early prevention strategies.

An international consortium analysis has shown that stroke location strongly predicts post-stroke cognitive impairment, but the effect could be confounded by the characteristics of the infarct and of different patients. Taking pre-stroke cognition and risk factors into consideration might put information about infarct location into a more appropriate context.

Results of two recent studies by Messoud Ashina and colleagues demonstrate that infusion of two different potassium channel openers can trigger migraine in humans; one of the compounds also triggered aura in patients diagnosed with migraine with aura. The findings highlight the importance of human experimental models in migraine research.

In patients with progressive multiple sclerosis, the presence of active inflammation is associated with improved efficacy of anti-inflammatory therapies. However, the frequency of active inflammation in this patient population is unknown, and is the subject of a new study.

The numeric clinical staging scheme in the 2018 NIA–AA research framework reflects the concept that symptoms of Alzheimer disease sit on a continuum rather than falling into distinct clinical categories. A recent study operationalized these clinical stages to evaluate their utility but found limitations in their application.

Chronic traumatic encephalopathy (CTE) is presumed to be associated with a clinical condition termed traumatic encephalopathy syndrome (TES). A new set of research diagnostic criteria for TES might be an improvement over previous guidelines, but many questions surrounding the putative link between head impacts, CTE neuropathology and neurobehavioural symptoms remain unanswered.

Biomarkers that predict conversion from isolated REM sleep behaviour disorder to Parkinson disease are urgently needed. A new study finds that detection of misfolded α-synuclein in the cerebrospinal fluid is a good marker of conversion risk, but an inability to predict the timeline of progression might limit its utility.

Apolipoprotein E (APOE) is the most abundant apolipoprotein in the brain, where it is primarily expressed and secreted by astrocytes and microglia. APOE seems to exert immunomodulatory effects in an isoform-dependent way, and a new study indicates that the APOE isoform dictates the glycosylation state and secretion of this apolipoprotein.

A recent report in Nature Cancer proposes that glioblastoma can be stratified into four functional subgroups on the basis of pathway inference from single-cell or bulk gene expression data. The analysis disclosed a pathway-based subgroup of glioblastoma that depends on oxidative phosphorylation and could potentially be targeted with mitochondrial metabolism inhibitors.

A recent study reports an improvement in migraine symptoms during a COVID-19 lockdown in the Netherlands. The findings suggest that lifestyle changes can substantially alter the course of migraine, opening the door for greater use of behavioural interventions alongside existing pharmacological therapies.