Reviews & Analysis

Tackling intertumoural and intratumoural heterogeneity is one of the most important challenges in the study and treatment of glioblastoma. A new anatomical transcriptional atlas of human glioblastoma associates established anatomical features with distinct molecular subclasses and provides open access to these well-annotated data for drug target validation and data-mining projects.

Free haemoglobin released from red blood cells after intracranial bleeding can lead to neurotoxicity and exacerbate injury. In this Review, the authors consider the biology behind haemoglobin toxicity and the clinical potential of targeting haemoglobin scavenging systems to aid recovery.

In this Review, the authors discuss all aspects of immune-mediated disorders of the CNS in children, from the clinical features and treatment to pathological mechanisms and biomarkers, and outline priorities for collaborative research to develop precision medicine for these disorders.

New research is increasingly challenging old notions of an immunologically isolated CNS. In this Perspectives article, Jun Chen and colleagues highlight discoveries on the beneficial roles of regulatory immune cells in brain repair and regeneration, and discuss their promise as therapies for neurological disorders.

Following on from a recent European Academy of Neurology guideline on pharmacological treatment of multiple sclerosis (MS), the American Academy of Neurology has issued an updated practice guideline on disease-modifying therapies (DMTs) for MS. The guideline provides 30 general recommendations for initiating, switching and stopping DMTs, and indicates future research directions.

Interest in tau-targeting strategies for Alzheimer disease is increasing, in part because of the failure of various amyloid-β-targeting treatments in clinical trials. Congdon and Sigurdsson review the current status of tau-targeting therapies, including anti-tau drugs and immunotherapies.

The WHO’s revised classification system for CNS tumours now incorporates genetic features, including the mutation status of isocitrate dehydrogenase (IDH) genes. A new article proposes that mutational status of CDKN2A and CDKN2B should also be included to facilitate grading of IDH-mutated gliomas with both prognostic and clinical relevance.

Cerebral small vessel disease (SVD) is associated with highly heterogeneous clinical symptoms. This Review considers how new advances in structural and functional neuroimaging have revealed ways in which focal lesions can affect remote brain regions and lead to global dysfunction, resulting in the variable presentation of SVD.

Frontotemporal lobar degeneration (FTLD) is a highly heterogeneous group of neurodegenerative diseases. This Review considers the phenotypic and genotypic differences among those with the most common form of FTLD—characterized by TDP43 pathology—with a view to improve patient care and facilitate current efforts to identify effective therapies for these individuals.

In this Review, Almad and Maragakis look at the technological advances that are transforming our understanding of astrocytes and explain how these techniques can be used to study neurological diseases in which astrocytes are important.

In a recent study, individuals with brain amyloid-β accumulation but no cognitive impairment were classified as being at risk of Alzheimer disease, yet amyloid-β is widely considered to be a pathological biomarker of Alzheimer disease rather than a risk factor — it cannot be both.

Japanese encephalitis remains the most commonly diagnosed epidemic encephalitis in the world despite the availability of vaccines, and new therapeutic strategies are sorely needed. Here, Turtle and Solomon summarize the epidemiology, clinical features, prevention and treatment of Japanese encephalitis and discuss the emerging challenges and opportunities for tackling the disease in humans.

An incomplete grasp of how the G₄C₂ repeat expansion in C9orf72 leads to amyotrophic lateral sclerosis and frontotemporal dementia has hindered progress in treatment development. Now, a study has combined unbiased genetic screens and CRISPR–Cas9 gene editing to validate known molecular pathways and identify novel therapeutic targets involved in G₄C₂ repeat pathogenesis.

Treatments that target calcitonin gene-related peptide (CGRP) and its receptor are proving effective for migraine treatment. In this Review, Edvinsson et al. trace the translation of CGRP biology into successful therapies and consider exactly where these drugs act.

Despite advances in the treatment of ischaemic stroke, functional outcomes are still suboptimal in many patients. Baron discusses approaches to further limit the spread of brain ischaemia by ‘freezing’ the penumbra — that is, the at-risk but not yet infarcted tissue.

Globally, access to neurological care remains limited for many people. However, technologies such as smart phones are now facilitating unprecedented access to remote care and specialist expertise. Here, Dorsey and colleagues discuss evidence of the benefits and risks of teleneurology for chronic disorders, including Parkinson disease, epilepsy and multiple sclerosis, as well as future trends and barriers to adoption.

New research has found that anaesthesia and surgery are associated with increased blood levels of two markers of neuronal injury — neurofilament light (NFL) and tau. The findings highlight the neurotoxic effects of anaesthesia and surgery and indicate that tau and NFL could present useful biomarkers for postoperative neurocognitive disorders.

Autoantibodies against the N-methyl-d-aspartate receptor (NMDAR) are known to cause encephalitis; however, a new study has identified anti-NMDAR antibodies in the absence of encephalitis in various mammalian species. These chronically produced natural antibodies might function in physiological target protein modulation and contribute to the symptoms of non-immune diseases.

Delayed treatment of status epilepticus is known to increase seizure duration, but new research shows that a delay of more than 10 minutes from seizure onset increases morbidity and risk of death. The findings emphasize the importance of time and suggest that status epilepticus should be treated as a medical emergency.

In this Review, Ahmed et al. look at the changes in physiological function that occur in neurodegenerative syndromes, consider the similarities and differences in these changes across conditions, and discuss the clinical utility of detecting these changes.