Review Articles in 2021

In this Review, Wiendl et al. consider how the study of rare but paradigmatic neuroimmunological diseases, including Susac syndrome, Rasmussen encephalitis and narcolepsy type 1, is providing fundamental insights into disease mechanisms that can be applied to more complex, heterogeneous neuroimmunological diseases such as multiple sclerosis.

Despite the declining incidence of variant Creutzfeldt–Jakob disease, prion diseases remain a threat to public health. In this Review, Suvankar Pal and colleagues provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance is still vital.

The failure to identify disease-modifying therapies for amyotrophic lateral sclerosis (ALS) could relate to the prevailing motor neuron-centric view of this neurodegenerative disorder. This Review considers the evidence for involvement of non-neuronal cells — in particular, microglia, astrocytes and oligodendrocytes — in ALS pathogenesis.

In this Review, Berg et al. summarize current understanding of prodromal Parkinson disease and consider the prodrome in the context of the clinical and pathological heterogeneity of the disease. They explore the possibility that prodromal Parkinson disease can be classified into subtypes.

In this Review, Wei and Goadsby discuss the pathophysiology of cluster headache, the treatments available and their mechanisms, and the insights being provided by results from trials of emerging treatments, which indicate mechanistic differences between episodic and chronic cluster headache.

In this Review, the authors provide an overview of the evidence for daily, multi-day and yearly cycles in epileptic brain activity. They also discuss advances in our understanding of the mechanisms underlying these cycles and the potential clinical applications of this knowledge.

Microglia are the first immune cells to encounter a developing primary brain tumour and have both tumour-supporting and antitumour effects. Here, Keane et al. consider the emerging evidence indicating that tumour-associated macrophages and microglia influence tumour initiation and progression as well as responses to therapy.

Impairments in prospective memory — that is, memory for future intentions, such as remembering to take medications — are observed in many neurological disorders. Henry reviews the manifestations and neural bases of prospective memory deficits and provides algorithms to guide evaluation and treatment.

The incidence and severity of Guillain–Barré syndrome (GBS) are increased in low-income and middle-income countries (LMIC) by distinct geographic, economic and environmental factors. Here, Papri and colleagues highlight the most important challenges and knowledge gaps relating to GBS in LMIC.

In this Review, the authors discuss the unique challenges involved in performing genetic testing for primary mitochondrial diseases and consider the value of advanced approaches such as long-read sequencing, RNA sequencing and the interpretation of transfer RNA variants.

Biomarkers of epileptogenesis would enable identification of individuals who are risk of developing epilepsy after an insult or as a result of a genetic defect. In this article, Simonato et al. review progress towards such biomarkers and set out a five-phase roadmap to facilitate their development.

Intraventricular haemorrhage (IVH) is a complication of preterm birth associated with neurodevelopmental sequelae. Here, Ballabh and de Vries review the mechanisms underlying IVH-induced white matter injury, focusing on its effects on oligodendrocyte progenitor cells, and discuss promising novel treatments for IVH-induced white matter injury.

In this Review, Chard and colleagues consider the effects that multiple sclerosis pathology has on brain networks and discuss the ways in which knowledge of brain network changes could inform the targeting of treatments for the condition.