Reviews & Analysis

Two new studies provide strong evidence for the link between mutations in the C9orf72 gene and familial frontotemporal dementia or amyotrophic lateral sclerosis. One of the papers presents some unique associations between clinical features and C9orf72 mutation, and raises questions regarding the specificity of some previously reported pathological findings.

The success of clinical trials in Huntington disease (HD) will depend to a large degree on the quality of the outcome measures. Using data from the TRACK-HD study, a recent publication proposes a battery of assessments that could be used as outcomes in future clinical trials in patients with early HD.

Pain is a frequent complication that is experienced by elderly individuals, including those with dementia. Corbett et al. highlight how pain might represent an unmet need in patients with cognitive impairment and review the best available evidence for tools and interventions to assess and treat pain in the context of dementia.

Promising results on newborn testing for Duchenne muscular dystrophy indicate that widespread screening could become routinely available. Nevertheless, newborn testing raises ethical, social and scientific concerns that need careful consideration to maximize benefit for patients, their families and health-care providers.

The higher incidence of multiple sclerosis (MS) in women than in men is widely acknowledged in the literature. The role of sex-related factors is, therefore, an important avenue for further investigation and for the development of novel therapeutic strategies for MS. In this Review, Voskuhl and Gold examine the effects of sex-related factors on MS susceptibility, activity and progression, and identify important areas for future research.

Recent analysis of treatment patterns and survival of newly diagnosed patients with glioblastoma in community settings in the USA has shown that the medical community rapidly adjusted to the new standard of treatment—the so-called 'Stupp regimen'. The findings are encouraging, but further research is needed to improve patient survival.

Diagnosis of dystonia—a syndrome of abnormal, involuntary movements—is difficult, given that many different underlying etiologies exist. Bertram and Williams review studies that investigated etiology in patients with various dystonic syndromes. On the basis of these data, the authors present an eight-question diagnostic approach that should enable both specialists and general neurologists to determine the appropriate diagnostic test for patients with a possible dystonic syndrome.

Recent guidelines, based on evidence of detrimental pharmacokinetic interactions between antiepileptic drugs (AEDs) and antiretroviral drugs, provide a new framework for the selection of AED medication for HIV-infected individuals. However, AED use, antiretroviral therapy and HIV infection all have overlapping nonpharmacokinetic outcomes, which the guidelines do not address.

Down syndrome (DS) is associated with early onset of neuropathology that is indistinguishable from Alzheimer disease (AD), and is typically followed by cognitive decline two decades later. A recent study has reported that the AD drug memantine failed to improve cognitive performance and function in middle-aged patients with DS.

The hippocampus is a dynamic structure that can change in size throughout life. Hippocampal atrophy, which is associated with cognitive decline and late-life dementia, can be exacerbated by a number of medical conditions. In this Review, Fotuhi and colleagues examine the modifiable factors that can affect hippocampal size, and discuss lifestyle and therapeutic interventions that might prevent or even reverse hippocampal atrophy.

Antiplatelet drugs are the treatment of choice for preventing recurrence of noncardioembolic ischaemic stroke, but numerous updates to clinical guidelines, most recently in 2011 in the USA, have made selection of the appropriate antiplatelet agent difficult. In their Review, Craig Williams and colleagues provide an overview of the evolving guidelines in the context of results from the many large clinical trials in this field.

Tourette syndrome is a complex neurobehavioural disorder that is believed to have a strong genetic component, but the exact aetiopathology of the disorder remains unclear. Denget al. provide an update on the genetics of Tourette syndrome, highlighting investigations into chromosomal aberrations and genetic mutations in patients with the disorder, and discussing how these studies have improved our understanding of the aetiology of Tourette syndrome.

An accepted classification system exists for ischaemic stroke in adults; however, this system is of limited use for categorizing strokes in children, as the aetiology of paediatric stroke is often different from that in adults. A new anatomically based classification system provides standardized criteria specifically for paediatric stroke.

MRI-based diagnostic criteria for multiple sclerosis (MS) have been devised for use in adult populations, but diagnosis of MS in children remains a challenge. To address this issue, a new study attempts to identify MRI characteristics that predict development of MS in children with acute demyelinating syndromes.

Therapeutic hypothermia is widely recognized to have neuroprotective effects in various clinical settings, from cardiac arrest to traumatic brain injury; however, the practical application of this therapy is not without risk. Choi et al. highlight current methods and protocols of targeted temperature management, and discuss the practical considerations for hypothermia as a therapy for patients with acute brain injury.

Self-projection allows an individual to remember the past, simulate the future and imagine the viewpoints of others, and seems to be mediated by key frontal and temporal lobe regions of the so-called default network of the brain. Irish and colleagues discuss pathological changes to the default network and self-projective functions in patients with frontotemporal dementia (FTD), focusing on behavioral variant FTD and semantic dementia.

Chronic migraine is a severely disabling condition that is poorly recognized and undertreated by clinicians. Much debate has existed over the nomenclature and diagnostic criteria for this condition and, until 2007, there had been a paucity of clinical trial data for preventive therapies. In this Review, Diener and colleagues discuss the evolution of terminology and definitions used for chronic migraine, as well as the epidemiology, pathophysiology and treatment of this condition.

Predicting response to therapy in individual patients with epilepsy is not straightforward. An exploration of long-term surgical outcomes in an epilepsy cohort has identified seven patterns of remission and relapse, and the probability of each outcome has been calculated. The study provides new predictors of postoperative outcomes in epilepsy.

Intensive glucose management, if begun early, diminishes the long-term complications of diabetes. Whether the cognitive domain also benefits from such therapy is not clear, and has remained subject to investigation. Do the new results from the ACCORD-MIND study settle the issue?

Genetically determined epilepsy with encephalopathy can develop early in life, often with prenatal onset, which makes diagnosis difficult. New molecular screening studies have identified causative mutations in patients with early-onset epilepsy with encephalopathy. What can we learn from the results of genetic screening in patients with this disorder?