Publications on epilepsy in 2018 have shed light on the aetiology and management of the condition and raised new questions. Translation from mechanisms to clinical practice, driven by cooperation among multiple fields, will be crucial to further advances.
Key Advances in Neurology
The Key Advances in Neurology collection offers a unique series of specially commissioned ‘Year in Review’ articles that highlight the key discoveries made each year. In these articles, leading experts in the field describe their pick of the top 3–5 key advances of the year, outlining their clinical impact and implications for current and future research.
The past year saw progress in acute treatment of ischaemic stroke, but large inequalities in stroke services were revealed, warranting strategical initiatives to improve treatment access. Reclassification of stroke as a disease of the nervous system in the WHO International Classification of Diseases 11th revision is likely to help such initiatives.
In 2018, the distinguishing pathological features of white matter lesions in patients with progressive multiple sclerosis (MS) were refined, and serological and MRI biomarkers of clinical worsening and evolution to progressive MS were identified. We also saw therapeutic advances in progressive MS with the emergence of new neuroprotective strategies and putative markers of neurodegeneration.
In the past few years the scientific community has witnessed a prodigious surge in research activity, publication of data and progress in understanding the mechanistic components of migraine. This renaissance is the result of efforts initiated decades ago that are finally being translated into benefits for individuals affected by this disease.
2018 saw the failure of several large clinical trials that were based on the premise that reduction of amyloid-β levels is an effective treatment for symptomatic Alzheimer disease. Yet, over the same time period, good news also emerged about the diagnostic value of tau PET imaging.
In 2018, developments in Parkinson disease (PD) research yielded improved diagnostic criteria and provided evidence for the effects of some treatments, both old and new. These developments enrich the treatment options available for PD and are likely to change important guideline recommendations.
In 2017, dramatic advances have been made in the treatment of motor neuron diseases. New therapies have been approved for spinal muscular atrophy and amyotrophic lateral sclerosis, and a host of other therapies that are currently under development are showing promising results.
2017 saw the publication of new classifications for epilepsy and seizure types, which emphasize the importance of understanding the underlying disease mechanisms. This aetiology-based approach is already beginning to inform developments in therapies and trial design in the epilepsies.
The past year saw advances in endovascular treatment for acute stroke, speech therapy for aphasia after stroke, and cardiac disease management to prevent stroke. These treatments were characterized by more intensive or more extensive effects than standard care, necessitating thoughtful translation of the clinical trial findings into routine clinical practice.
200 years after James Parkinson's An Essay on the Shaking Palsy, 2017 has seen important advances that are driving a shift towards a broader and more holistic understanding of Parkinson disease aetiology and progression. This shift might finally pave the way to entirely novel and more effective prevention and management strategies.
In 2017, extensive research into multiple sclerosis (MS) resulted in improved diagnostic criteria, development of biomarkers that enable monitoring of disease evolution and treatment response over time, and identification of novel genetic markers of disease susceptibility. In addition, 2017 saw the first successful clinical trials of remyelination strategies and treatments for progressive MS.
In 2016, the literature on neurological infections was, understandably, dominated by Zika virus. However, we should not overlook important publications on the treatment of cryptococcal and bacterial meningitis.
Brain tumours encompass a heterogeneous collection of neoplasms, traditionally classified by histopathological criteria. In 2016, the WHO published an updated classification that, for the first time, defines brain tumour types according to integrated histological and molecular parameters. Furthermore, clinical trial results were reported that inform therapeutic decision-making in diffuse gliomas.
In 2016, new highly active treatment options for relapsing–remitting multiple sclerosis (MS) emerged. At the same time, large clinical trials in progressive MS highlighted the limitations of immune-directed therapies, and called for new strategies to treat disease progression in MS.
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.
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.
The past 2 years have seen major breakthroughs in endovascular treatment for acute ischaemic stroke. As highlighted in 2016, we now need to refine the logistics for delivery of this treatment, including patient selection. We should not forget, however, that it is better to prevent strokes in the first place.
Current related Reviews
New technological advances in genomics have enabled the rapid discovery of hundreds of gene mutations linked to epilepsy. This Review considers the prospects for precision medicine in genetic epilepsies, the use of conventional and novel experimental models to unpick the complex pathogenic mechanisms of these diseases and the opportunities and challenges that face basic and clinical researchers.
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.
In this Review, Khalil et al. consider how technological advances have enabled the detection of neurofilament proteins in the blood, and discuss how these proteins consequently have the potential to be easily measured biomarkers of neuroaxonal injury in various neurological conditions.
In clinical trials, outcome measures might determine whether a drug is worthy of further development; in the clinic, they might guide important treatment decisions. Here, Tur and colleagues help clinicians and researchers navigate the maze of options for clinical, neuroimaging, patient-reported and composite outcome measures in multiple sclerosis.
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.
Potential disease-modifying therapies for Alzheimer disease have mostly targeted brain accumulation of amyloid-β, but this approach has yet to provide substantial clinical benefits. The authors consider the reasons for this failure and suggest alternative strategies, including modification of risk factors.
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.
Deep brain stimulation is used to treat a variety of neurological conditions, including Parkinson disease, dystonia and intractable pain, but the mechanisms underlying its therapeutic effects remain unclear. Drawing on clinical and experimental data, the authors examine hypotheses that have been proposed to explain the effects of DBS, and present the case for a change in terminology to 'deep brain neuromodulation'.
In this Perspectives article, Espay and colleagues argue that that the adoption of precision medicine in Parkinson disease will require a revision of biomarker development efforts, with the ultimate goal of testing putative disease-modifying interventions in well-defined disease subgroups.