Reviews & Analysis

Glioblastomas remain one of the most aggressive and lethal tumours, with no effective treatments available. Here, Xandra Breakefield and colleagues examine the ways in which glioblastomas manipulate brain cells and immune cells in their environment to support tumour growth and the opportunities available for new therapies that disrupt these interactions.

In this Review, Ferretti et al. discuss the evidence for sex-related differences in Alzheimer disease symptoms, progression, risk factors and treatment, and consider how understanding sex differences is crucial in developing precision medicine.

This Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed Alzheimer disease with a focus on using spatial navigation as a diagnostic tool. Research gaps and future research priorities are also identified.

Non-rapid eye movement (NREM) sleep parasomnias are thought to derive from incomplete arousal from NREM sleep. Here, the authors present evidence for coexistence of sleep-like and wake-like brain activity in disorders of arousal, including confusional arousals, sleep terrors and sleepwalking.

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.

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.

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.

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.

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.

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.

Complex regional pain syndrome (CRPS) is a persistent pain condition that usually affects a single limb, often following an injury. In this article, the authors review the latest advances in CRPS research, focusing on risk factors for the condition as well as biomarkers for diagnosis, treatment and clinical course prediction.

In this Review, MAGNIMS provides an update on the imaging features that differentiate multiple sclerosis (MS) from its most common imaging mimics and a summary of the red-flag MRI features that indicate a diagnosis other than MS.

The epidemiology, risk factors, causes, treatment and outcomes of intracerebral haemorrhage (ICH) in young adults (aged ∼18–50 years) can differ markedly from those in elderly patients with ICH. Challenges in this setting include high early mortality and long-term mortality as well as long-term disability and ICH recurrence in survivors.

Villemagne and colleagues describe advances in neuroimaging using selected amyloid-β (Aβ) and tau tracers. Aβ and tau neuroimaging can identify proteinopathies in at-risk patients, facilitating the early and accurate diagnosis of neurodegenerative disease. Applications of Aβ and tau neuroimaging in staging and monitoring of disease and treatment selection are also discussed.

Approval of the first disease-modifying therapy for spinal muscular atrophy (SMA), the antisense oligonucleotide nusinersen, represents a major breakthrough in neurodegenerative disease research but also has important medical, ethical and financial implications for SMA and beyond. This Review considers the current and future landscape for SMA therapy and the challenges and opportunities that are emerging.