Reviews & Analysis

Migraine affects up to 25% of women of reproductive age. Suboptimally treated migraine during pregnancy can negatively affect both mother and fetus, but few data exist on the safety of many commonly used pharmacotherapies for migraine. This Review summarizes current evidence on the safety of the most common antimigraine drugs during pregnancy and breastfeeding, and provides treatment recommendations for clinical practice.

Sports-related concussion is increasingly recognized as a potential danger to paediatric populations, but its short-term and long-term consequences remain poorly understood. This Expert Consensus Document is the result of a 1-day meeting convened by Safe Kids Worldwide, the Alzheimer's Drug Discovery Foundation, and the Andrews Institute for Orthopaedics and Sports Medicine, with the aim of highlighting knowledge gaps and areas of critically needed research in youth sports-related concussion.

The randomized controlled trial represents the gold standard in clinical trial design, but large phase III studies are difficult and expensive to conduct in neurological diseases. In this Perspectives article, Koch and colleagues argue that the futility trial, a phase II design first developed in the oncology field, should be used more widely by neurologists. The authors describe how futility trials could be employed in Parkinson disease, stroke, multiple sclerosis and other conditions.

Research into Friedreich ataxia has been hampered by low availability of study participants. Now, a European consortium has released baseline data from a continuing study of 592 patients with Friedreich ataxia, providing information on clinical features and progression. Such large cooperative studies might herald the final battle against this disabling disease.

A recent study has found that one in six people who are independent at 3 months after stroke deteriorate and need assistance by 12 months. Older women with comorbidities, and patients not given appropriate secondary stroke prevention were most at risk. Anticipation and prevention of deterioration could help reduce the later burden of stroke.

Stroke has a heavy socioeconomic burden. A subset of patients with transient or nondisabling cerebral ischaemic events will experience recurrent stroke, leading to permanent deficits. Two new studies tackle the challenge of identifying the patients most at risk for recurrent stroke via examination of radiological and serum biomarkers.

Type 2 diabetes mellitus (T2DM) has been linked with cognitive impairment and dementia. A new cross-sectional study reports that T2DM is also associated with dementia in Parkinson disease, and another study describes the long-term clinical course of diabetes-associated cognitive dysfunction; however, the mechanisms through which T2DM affects the brain are not completely understood.

White matter hyperintensities (WMHs) are frequently seen on brain MRI in older people, and are thought to result from chronic ischaemia associated with cerebral small vessel disease. Prins and Scheltens provide a timely Review on WMHs, including their relationship with cognitive decline and dementia. The authors also discuss how WMHs might provide a therapeutic target to prevent the onset and progression of dementia.

Age related hearing impairment (ARHI, also known as presbycusis) is an important frailty marker, and could be a reversible risk factor for dementia and Alzheimer disease. Poor verbal communication and depletion of cognitive reserve might causally link ARHI to cognitive decline and frailty; hearing aids and cognitive training might, thus, provide a strategy to delay or prevent cognitive deterioration. In this Review, Panza and colleagues discuss the interplay between cognitive impairment, ARHI and frailty in older age.

The past 20 years have seen remarkable progress in research into multiple sclerosis (MS), resulting in a veritable armamentarium of treatment options. Ransohoff and colleagues reflect on three major eras of drug development to date. The authors also offer guidance on how best to select between various therapeutics, and look to the future of MS research.

Neuroinflammation during critical phases of brain development can increase the risk of neurological and neuropsychiatric disorders, even in adulthood. In this Review, Hagberg et al. review the mechanisms through which inflammation can exacerbate perinatal brain injury, and outline how understanding the interplay between inflammation and brain injury can aid the identification of new strategies to alleviate neurological and neuropsychiatric morbidity.

Approximately 60% of people diagnosed with childhood-onset epilepsy are known to be in 5-year remission and off medication, or in complete remission. A new report confirms and consolidates these findings and gives further evidence of the long-term stability of remission in epilepsy. A future risk of relapse is suggested, which might be an overestimate.

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.

Mounting evidence suggests that autoantibodies contribute to the pathogenesis of demyelination in the PNS and CNS, and that such autoantibodies might impair saltatory conduction mediated by the node of Ranvier. In this Review, the authors provide a detailed description of the molecular anatomy of the node of Ranvier, discuss nodal, paranodal and juxtaparanodal proteins as likely autoantigens, and examine the role of autoantibodies in the pathogenesis of demyelinating disease.

Perihaematomal oedema (PHO) is an important pathophysiological marker of secondary injury following intracerebral haemorrhage. In this Review, the authors consider PHO in a novel framework and highlight the clinical relevance of the condition, both as a therapeutic target and as a surrogate marker for novel interventions that target secondary injury.

In this Review, Mead and Reilly present a new form of prion disease, characterized by systemic amyloidosis, diarrhoea, neuropathic pain and postural hypotension. So-called PrP systemic amyloidosis is caused by mutations in the prion protein gene that result in a premature stop codon, and all mutations identified to date are autosomal dominant. The authors recommend a standardized and conservative approach to the diagnosis and treatment of patients with PrP systemic amyloidosis.

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.

Deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus internus can substantially improve appendicular motor symptoms of Parkinson disease (PD); however, the effect of DBS on axial motor signs—such as gait impairment, postural instability and postural abnormalities—is less clear. In this practically oriented Review, Fasanoet al. discuss the most important considerations to establish the reasons for gait problems in patients receiving DBS, and suggest how to manage axial disability in these patients.

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.