Reviews & Analysis

Over the past two decades, trials of citicoline for treatment of acute stroke have produced conflicting results. A recent large clinical trial of citicoline in acute stroke suggests a lack of efficacy of this therapy, seemingly signalling the end to the citicoline saga.

An evidence-based update to the 2004 guidelines for the treatment of infantile spasms has recently been published. Important new recommendations include use of low-dose adrenocorticotropic hormone (ACTH) over high-dose ACTH or vigabatrin. A paucity of data, however, leaves several key questions unanswered.

EEG source imaging (ESI) is a technique designed to predict the source of a given field potential obtained using EEG. Kaiboriboonet al.describe the principles and technical aspects underlying ESI in epilepsy. They discuss the practicalities and pitfalls of ESI in the clinical setting, specifically for epileptic source localization and identification of the eloquent cortex—two important considerations when planning resective surgery in patients with refractory epilepsy.

Restrictions to thrombolytic therapy for stroke—recommended only up to 4.5 h after onset and in those under 80 years of age—limit its use. Results from a recent trial support expansion of both the inclusion criteria and the time window for thrombolytic therapy, but further research is needed.

Next-generation sequencing approaches are becoming increasingly affordable for use in the clinical setting, and have the potential to provide valuable insights into the genetic underpinnings of complex neurological diseases. In this Review, Foo et al. discuss how whole-genome and whole-exome sequencing data can be deciphered, and consider how such data might be used for diagnosis and risk prediction in the neurology clinic.

Cerebral malaria is a potential, severe outcome of Plasmodium falciparum infection, but the molecular basis of this complication has been unclear. Three recent studies have identified specific var genes encoding the malaria parasite ligand that binds to human brain endothelial cells, pointing to therapeutic targets for cerebral malaria.

Recent studies suggest that advances in medical therapy have reduced the risk of stroke in patients with major cerebral artery disease, but does this trend apply to those with misery perfusion? A new study indicates that these patients remain at very high risk, highlighting the unmet need for a preventative treatment.

Multiple sclerosis (MS) is an inflammatory disorder of the CNS, with downstream effects on body structures and function, and patient activities, as outlined in the International Classification of Functioning, Disability and Health (ICF) model of MS. Focusing on the ICF outcomes, Motl and Pilutti review evidence regarding the benefits of exercise training in patients with MS, highlighting the mechanistic pathways that may mediate these effects, and discussing issues and future research in this field.

Variant forms of Alzheimer disease (AD) exist that are associated with amyloid deposition in the brain but have disparate clinical features. In this Review, the authors argue that selective vulnerability of a core functional network could explain the clinical heterogeneity of disease symptoms in atypical AD and other neurodegenerative disorders.

Cognitive difficulty in patients with epilepsy is often thought to result from poor control of the disorder. A recent study, however, supports previous observations that cognitive impairment is common at initial presentation. Should methods for establishment of cognitive impairment be considered as part of routine evaluation in patients with epilepsy?

Advanced-stage Parkinson disease (PD) is characterized by motor complications caused by dopaminergic therapy and has long been recognized. With the introduction of deep brain stimulation, however, patients are increasingly progressing to later stages of disease, which feature nonmotor symptoms such as dementia, and treatment-resistant motor symptoms including falls. Coelho and Ferreira discuss disease progression from the advanced stage onwards, and propose a functional definition of late-stage PD.

Subarachnoid haemorrhage (SAH) is a type of stroke that is associated with substantial morbidity, requiring neurosurgical and intensive medical management. Recent guidelines for the management of SAH highlight current knowledge and issues that remain to be resolved, and are essential reading for physicians who treat individuals with this condition.

Immunotherapy targeting amyloid-β showed promise for treatment of Alzheimer disease (AD) in preclinical studies, but trials in humans have yielded disappointing results. In their Perspectives article, Liu and colleagues discuss adverse effects of amyloid-targeted therapies, which have limited treatment efficacy, and propose strategies to optimize the design of future therapeutic antibodies for AD.

Carotid endarterectomy reduces the risk of stroke in patients with symptomatic carotid artery stenosis, but the optimum time to perform surgery has been uncertain. A large study has shown that surgery within 2 days of stroke or transient ischaemic attack has an unacceptable complication rate, but is safe thereafter.

Given the national deficit in available organs for transplantation, substantial motivation exists to enhance procurement in the area of donation after cardiac death. This article reviews a new predictive tool that aims to identify donors dying within the viable time frame while reducing the human and resource implications of unsuccessful attempts.

Over the past decade, numerous studies have identified the causative genes and pathological proteins in most cases of frontotemporal dementia (FTD). Most recently, abnormal repeat expansion in theC9orf72 gene was identified as a major cause of the disorder. Rademakers et al. discuss how these discoveries have improved our understanding of the molecular basis of FTD, and highlight how these findings will translate into improved patient care.

In April 2012, the American Academy of Neurology and the American Headache Society issued new guidelines on preventive treatment for episodic migraine. Although the guidelines provide valuable information regarding drug efficacy, they do not address the equally important issue of adverse events.

Two recent studies have carefully characterized amyloid-related brain insulin resistance in animal models of, and patients with, Alzheimer disease (AD). The researchers show that exendin-4, a glucagon-like peptide 1 receptor agonist, ameliorates pathology and symptoms in a mouse model of AD, suggesting a novel therapeutic approach to this disease.

A new concept in stroke emergency care is to bring specialized units and neuroimaging facilities to the patient in order to reduce time to treatment. But does this strategy have an effect on stroke outcome, and is the cost of these units worth the time saved?

Autoantibodies that target neuronal proteins are becoming increasingly recognised. Lancaster and Delmau provide an overview of antibodies with intracellular neuronal targets, together with more-recently characterized antibodies against cell-surface and synaptic antigens, such as neurotransmitter receptors. The authors describe the pathogenic mechanisms of these antibodies and the associated disorders, and provide guidelines for rigorous antibody testing in patients with suspected neuronal autoantibodies.