Volume 9 Issue 11, November 2013

A recent study has examined potential predictive markers of Alzheimer disease (AD) and stroke. The results challenge some current assumptions, suggesting that stroke might often follow a decade of deterioration in brain structure and function, and that cognitive and MRI markers of AD differ in older and younger individuals.

Patients with epilepsy have a higher mortality rate than the general population. A recent population-based study has found that external causes of death, such as suicide and accidental deaths of various types, account for 16% of the deaths in these patients, and that psychiatric comorbidity contributes significantly to their occurrence.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) study protocol currently precludes disclosure of test results to participants. A survey among ADNI investigators, however, demonstrates that most want this policy changed, in light of the approval of ¹⁸F-florbetapir as a PET amyloid ligand. Should we tell the study participants if they want to know?

Gene therapy approaches for glioblastoma multiforme (GBM) have been under investigation in clinical trials since the 1990s, but the results to date have been disappointing. A recently published phase III trial of adenovirus-based gene therapy for GBM has demonstrated modest—but possibly clinically relevant—improvements in patient survival.

An evidence-based guideline update on vagus nerve stimulation for treatment of epilepsy supports consideration of its use in children, in patients with Lennox–Gastaut syndrome, and to improve mood in adults. Its efficacy may also increase over prolonged treatment. These conclusions are tentative, however, highlighting our knowledge gaps.

Identification of the key factors involved in glioblastoma oncogenesis is a necessary precursor to the development of efficient and personalized, targeted therapy. Combining data from high-throughput genetic screening, bioinformatic analysis and functional studies, a multicentre research collaboration has identified new driving mutations in glioblastoma, including novel tumour suppressor and fusion oncogenes.

New research indicates that next-generation sequencing (NGS) can improve the diagnostic yield in a highly selected group of patients with ataxia, following comprehensive exclusion work-up of other causes. However, routine practical application of NGS will depend on refinement of current technologies to facilitate data interpretation, and cost-effectiveness analysis in different patient groups.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons that results in relentlessly progressive paralysis and, ultimately, death. Considerable progress has been made in elucidating the genetic causes of ALS, but the contribution of environmental factors has been more difficult to determine. Al-Chalabi and Hardiman outline the current state of knowledge regarding the environmental and genetic epidemiology of ALS, and propose a disease model in which environmental risks and time act on a pre-existing genetic load.

Parkinson disease (PD) pathogenesis involves dysfunction and eventual death of midbrain dopaminergic neurons. Emerging evidence points to a role for the transcription factor NURR1 in this process. In this Review, the authors describe findings from animal and human studies that support this concept, outline possible underlying mechanisms involving oxidative stress and interaction with α-synuclein, and highlight the potential of NURR1 as a therapeutic target.

Cortical spreading depression (CSD) is a wave of activity that propagates across the brain surface, and has long been presumed to be the physiological substrate of the migraine aura. Despite substantial evidence from animal models, however, the relationship between CSD and migraine in humans remains uncertain. Charles and Baca review our current understanding of the role of CSD in migraine, and highlight the unresolved issues in this field of investigation.

Intravenous thrombolytic therapy is the only approved treatment for acute ischaemic stroke, but the majority of patients do not benefit from, or are ineligible to receive, such treatment. Angiographically guided recanalization of the occluded vessel through use of a stent retrieval device offers the potential to effectively restore blood flow in patients with ischaemic stroke, and has shown promise in early-stage trials. Jansen and Rohr review advances in such neurothrombectomy techniques and summarize completed and ongoing trials. The authors outline important considerations when selecting patients for this intervention.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischaemic stroke, although its use for patients with mild forms of this condition remains controversial. Here, Guerrero and Savitz outline the potential risks and benefits of rtPA in this patient population, and explain why they believe patients with mild ischaemic stroke should receive this treatment.