Reviews & Analysis

Verhaart and Aartsma-Rus discuss important advances in the treatment of Duchenne muscular dystrophy. Gene-addition, exon-skipping, stop codon readthrough and genome-editing approaches aim to restore expression of partially functional dystrophin, whereas treatments that target disrupted pathophysiological pathways can improve muscle function.

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.

The latest revision of the McDonald criteria for the diagnosis of multiple sclerosis (MS), released in 2017, was designed to facilitate early diagnosis of MS. Here, a panel of world-renowned MS specialists share their personal experiences of the new criteria.

In the future, robotic devices that augment human care provision could transform dementia services and support. In this Perspectives article, Moyle discusses upcoming challenges in dementia care and suggests guidelines for the development and integration of smart assistive technologies.

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.

Vaughn et al. review the challenges facing elderly patients with multiple sclerosis (MS). They describe the complex, evolving relationship between ageing and MS pathophysiology, highlight the lack of evidence for the safety and efficacy of disease-modifying therapies in elderly patients, and discuss treatment discontinuation and wellness strategies.

In this Review, the authors discuss findings that are transforming our understanding of neuropsychiatric diseases and the role of inflammation in these disorders. They suggest new diagnostic and therapeutic criteria for the emerging field of neuroimmunopsychiatry.

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.

Personalized multiple sclerosis therapy depends on evidence-based prognostication, an initial treatment choice and evaluation of early treatment responses to identify the need to switch therapy. In this Review, Rotstein and Montalban discuss the factors that need to be taken into account to make personalized treatment decisions.

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?

Here, Bouthour et al. argue that the success of closed-loop deep brain stimulation based on electrophysiological biomarkers in patients with Parkinson disease could inspire novel treatments for other neuropsychiatric disorders in which symptoms are driven by pathological activity in motor, cognitive and limbic brain networks.

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.

Organic acidurias (OADs) are inherited neurometabolic diseases usually caused by deficiencies in enzymes involved in amino acid catabolism. Wajner reviews the main features of the OADs, focusing particularly on the cerebral manifestations, and highlights recent advances regarding pathophysiology and treatment.

In this Review, Nedelsky and Taylor review the evidence that disturbances in phase transition dynamics and the material properties of ribonucleoprotein granules underlie the pathogenesis of many neurodegenerative diseases, including forms of amyotrophic lateral sclerosis and frontotemporal dementia, among others.

Conventional therapies for Parkinson disease (PD) include dopamine replacement and therapies targeting symptomatic relief, but these approaches fail to modify the underlying disease. This Review explores the novel PD treatment strategies currently being investigated, including pharmaceuticals, cell therapies, immunotherapies, gene therapies and new technologies.

A new study, using a mouse model of multiple sclerosis, applied single-cell RNA sequencing to determine how immune cells in the CNS respond during inflammation. In addition to highlighting novel subtypes of cells that evolve over the course of disease, the findings have important implications for developing targeted therapies for inflammatory demyelinating diseases.

The risk of Alzheimer disease is substantially influenced by genetic factors. A new genome-wide association study of more than 600,000 individuals identifies nine novel Alzheimer disease risk genes, raising the total count of independent risk loci to 29.

The opioid crisis constitutes a public health challenge at the intersection of two interrelated medical problems — opioid addiction and chronic pain. In this Perspectives article, Volkow and Koroschetz discuss how neurologists are uniquely positioned to help address the opioid crisis.

Parkinson disease is a clinicopathological construct at a crossroads. A new study reinforces the prognostic value of subtypes, but its findings challenge the relevance of pathology to the clinical expression of disease as data-driven Parkinson disease subtypes did not match up with severity or distribution of Lewy or Alzheimer pathologies.