Year in Review

In the field of movement disorders, areas that have seen important advances in 2016 include the pathogenesis of Parkinson disease involving extra-CNS α-synuclein pathology, treatment of hyperkinetic disorders with novel dopamine-depleting drugs, and MRI-guided ultrasound surgery for the treatment of essential tremor.

Investigational treatments to impede the progression of Alzheimer disease (AD) are being evaluated in clinical trials, and biomarkers to detect and track the disease are being developed and deployed. Recent findings underscore the importance of ongoing clinical trials and biomarker developments in the understanding, treatment and prevention of AD.

The application of imaging biomarkers has provided new insights into the mechanisms of damage in multiple sclerosis (MS) and the risk of MS development and progression. The goal of eliminating all disease activity requires a timely escalation of treatment. This increasing complexity is compounded by the need to treat comorbidities.

Diagnosis and management of epilepsy remain challenging, particularly among women of child-bearing age. In 2015, notable steps were taken in the right direction, with work that provided insight into the diagnosis of epilepsy, management of this condition during pregnancy, and new treatment options.

Tau protein abnormalities are key pathogenic features of Alzheimer disease and other neurodegenerative diseases. In 2015, new studies of the less common tauopathies, including progressive supranuclear palsy, chronic traumatic encephalopathy and frontotemporal lobar degeneration, have identified in vivo biomarkers and mechanisms that initiate tau pathology.

Important advances in Parkinson disease (PD) in 2015 included a revision of its clinical diagnostic criteria and a proposal for research criteria defining prodromal PD. Research published in the past year has also continued to expand our understanding of the roles of Lewy pathology and α-synuclein in the pathobiology of PD.

Gliomas are the most common form of malignant primary brain tumour. In the past year, substantial progress has been made in the classification and treatment of lower-grade gliomas (WHO grades II and III), and the FDA has approved a new therapy for newly diagnosed glioblastomas.

The past year has seen practice-changing findings in stroke research. Strong evidence now supports endovascular thrombectomy as the new gold standard of care in acute ischaemic stroke, and a pragmatic trial raised concerns over early intensive mobilization after stroke. Moreover, new insights were gained into the trajectory of stroke-associated cognitive decline.

Improved neuroimaging and molecular markers of Alzheimer disease (AD) have aided diagnosis of AD in the very early stages, and have facilitated differential diagnosis between AD and other neurodegenerative disorders with dementia. The finding that some older individuals can show amyloid-β pathology while remaining cognitively intact raises important questions regarding prevention strategies.

The past year saw the 40^th anniversary of the Glasgow Coma Scale, which continues to be effective for monitoring patients with traumatic brain injury. Three new clinical trials were completed, but none revealed beneficial interventions. These failures have prompted exploration of more-subtle therapy targets, novel disease classifications and collaborative research paradigms.

Scientific progress in multiple sclerosis (MS) research spanned a number of areas in 2014, including therapeutics, disease classification, risk management, and disease mechanisms. Advances were particularly notable in the field of progressive MS. Altogether, the findings move us one step closer to a better understanding of this complex disease.

In 2014, novel, large-scale collaborative efforts and frameworks resulted in major advances in the epilepsy field, from publication of a new definition of epilepsy to important discoveries regarding aetiology, pathophysiology and management. These collaborative works provide a platform from which further advances are anticipated, and a model for future research.

Genetic revelations in 2014 are testing traditional classification systems for movement disorders, and our approach to clinical diagnostics. Mutations in dystonia-associated genes lead to a spectrum of disorders with different phenotypes, underscoring the need for stringent clinical phenotyping of patients with movement disorders, as well as next-generation sequencing approaches.

The past year has seen some extraordinary activity in clinical amyotrophic lateral sclerosis (ALS) research. Two trials were completed, with negative results, but the discovery of novel ALS-associated genes, and body fluid and imaging biomarkers warrants cautious optimism. Here, we provide a snapshot of some of the main findings in 2014.

In 2013, two discoveries—that alkylating agent chemotherapy prolongs survival when added to radiotherapy for patients with anaplastic oligodendroglial tumours with 1p19q codeletion, and that bevacizumab prolongs progression-free survival in patients with newly diagnosed glioblastoma—have dominated debate in neuro-oncology. These findings could help to define new standards of care in malignant glioma.

Over the past year, we have witnessed major advances in several areas of epilepsy research, including genetics and disease mechanisms, neurodevelopmental effects of antiepileptic drugs, and new therapeutic approaches based on closed-loop neurostimulator systems. The findings have important implications both for clinical practice and for future research.

Genetic research in frontotemporal lobar degeneration (FTLD) is gaining momentum. Following the discovery of a repeat expansion in the gene C9 open reading frame 72 (C9orf72), three major genes and associated disease mechanisms and inclusion body pathologies have emerged, paving the way for personalized medicine in FTLD.

2013 witnessed advances in many aspects of multiple sclerosis (MS) research. Two studies highlighted a potential role for salt as an MS trigger, and one immunomodulatory drug performed well in clinical trials. Moreover, treatment effects of MS drugs were shown to correlate inversely with brain atrophy and disease progression.

Clinical trials in stroke intervention during the past year have yielded contrasting results. Endovascular therapies and procedures to reduce stroke risk caused by patent foramen ovale have failed to demonstrate superiority over standard medical treatments. By contrast, a trial of neuroprotection—traditionally thought to be ineffective in humans—offers hope.

When the motor symptoms of Parkinson disease (PD) manifest, the underlying pathological processes have already caused irreversible damage. Research breakthroughs in 2013 support the importance of diagnosing PD in the prodromal phase, suggest biomarkers that could help in identifying patients at high risk of PD, and improve upon current deep brain stimulation strategies.