Review Articles

Currently, idiopathic Parkinson's disease can only be diagnosed definitively by the demonstration of intracellular Lewy body inclusions on histological specimens of brain tissue—an approach that is impractical in living individuals. In this Review, David Brooks discusses recent advances in noninvasive imaging approaches that are providing important insights into the structural, pathophysiological and pharmacological changes associated with Parkinson's disease, and could have major implications for the future diagnosis and management of this condition.

Neuromyelitis optica (NMO) is a rare neuroinflammatory disorder that predominantly affects the optic nerves and spinal cord. NMO was originally considered to be a subtype of multiple sclerosis, but the recent discovery of NMO-specific serum autoantibodies has caused it to be reclassified as a distinct disease. In this article, Jariuset al. review clinical, serological and pathological findings in NMO, and discuss the evidence supporting an antibody-mediated mechanism in its pathogenesis.

Although there have been substantial innovations in antiepileptic drug therapy over the past 15 years, the proportion of patients with medically refractory epilepsy has remained largely unchanged, highlighting the need for new therapeutic strategies. In this article, Stacey and Litt review recent progress in the development of implantable devices designed to detect, predict and extinguish seizures, and consider the challenges that lie ahead, including improvements in seizure prediction and personalized control.

Over the past century, the pathophysiology of ischemia in the borderzones between the large cerebral arteries has been the topic of considerable debate. Two seemingly mutually exclusive mechanisms—hemodynamic failure and microembolism—have been proposed to explain this phenomenon. As Förster et al. discuss in this article, a new model of borderzone infarction, incorporating both hypoperfusion and microembolism, is now emerging.

Duchenne muscular dystrophy is an X-linked recessively inherited disorder of skeletal and cardiac muscle that is caused by mutations in the dystrophin gene. In this article, Lim and Rando describe new mutation-specific therapeutic strategies that use nonviral agents to target nonsense point mutations or frameshift deletions at the dystrophin locus, with the ultimate aim of developing 'personalized' gene therapy for Duchenne muscular dystrophy.

Autism spectrum disorders (ASDs) are characterized by qualitative impairments in the development of social and communication skills, often accompanied by stereotyped and restricted patterns of interests and behaviors. ASDs are usually diagnosed between the ages of 3 and 6 years, but, as Rebecca Landa discusses in this Review, there is increasing evidence that a diagnosis can be made in the second year of life in some children. She argues that early diagnosis and intervention are likely to lead to improved outcomes in children with ASDs.

Inflammatory responses to CNS infections can cause severe disability or even death, and pharmacological treatments that dampen inflammation might, therefore, be beneficial adjunctive treatments in such cases. In this article, Fitch and van de Beek review the available evidence that steroids, administered in conjunction with appropriate antimicrobial therapy, can improve outcomes in patients with bacterial meningitis, tuberculous meningitis or herpes simplex virus encephalitis.

To devise therapeutic strategies for the rehabilitation of patients with hemiparetic stroke, it is important to understand the mechanisms that underlie the neuroplasticity induced by skills training and exercise programs. In this Review, Dobkin considers how basic neurobiological mechanisms might be exploited to enhance motor recovery after stroke, and to enable patients to participate more fully in activities of daily life.

Oxidative stress seems to be a common factor in the pathogenesis of inherited ataxias, prompting attempts to treat these conditions with antioxidants. In this Review, Massimo Pandolfo discusses the rationale for antioxidant treatment in inherited ataxias, and describes the results of the clinical trials conducted to date, focusing particularly on the use of coenzyme Q analogs to treat Friedreich ataxia.

Axon degeneration is a major contributor to disability in multiple sclerosis, and sodium channels have been shown to have a crucial role in this process. In this article, Waxman reviews the development of the concept of sodium channel blockers as neuroprotectants in multiple sclerosis, and discusses recent attempts to translate this approach from the laboratory to the clinic.

The role of statins in primary stroke prevention is well established, but, until recently, their benefits with regard to secondary prevention of vascular events in patients who had already experienced a stroke or transient ischemic attack were less certain. In this article, Sanossian and Ovbiagele review the findings of the Stroke Prevention through Aggressive Cholesterol Levels (SPARCL) trial, which showed that an intensive statin regimen can protect against secondary stroke and other major vascular events. They also outline current guidelines for the use of statins in patients with stroke.

It is becoming increasingly clear that the female population carries a larger stroke burden than the male population, partly because of increased life expectancy, and partly because most deaths from stroke occur in women. In this article, Cheryl Bushnell reviews our current knowledge regarding sex-related differences in stroke characteristics and risk factors, including the influence of endogenous and exogenous estrogens. She also describes a new initiative designed to advance the study of stroke in women.

Arterial dissections are one of the most common forms of vascular lesion to affect the cervical carotid and vertebral arteries, second only to atherosclerosis. Arterial dissections are often caused by sudden or unusual stretching of arteries in the neck or head, and can occur as a complication of chiropractic and other neck manipulations. In this article, Louis Caplan reviews the underlying causes and clinical features of dissections of brain-supplying arteries and outlines the current recommendations for treatment of these lesions.

A range of impulse control disorders (ICDs), including pathological gambling, compulsive shopping and impulsive aggression, has been recognized in patients with Parkinson's disease (PD). This Review provides the neurologist with an understanding of the clinical and biological features of ICDs and the nature of their relationship with PD. The authors also offer guidance on the management of PD patients with an ICD.

Despite advances in treatment approaches for patients with high-grade glioma, the overall prognosis remains poor. In this article, Castellino and Durden highlight the important role of angiogenesis in the pathogenesis of brain tumors, and discuss the development of new therapies that target angiogenesis in high-grade glioma by regulating the activity of the PI3K–Akt–PTEN signaling node.

It is estimated that around one-third of patients with new-onset epilepsy will eventually develop medically intractable seizures. Many patients with intractable epilepsy are likely to benefit from surgery, which, by controlling the seizures, can substantially improve quality of life and reduce the costs of medical care. In this article, Kuzniecky and Devinsky review the current surgical management of epilepsy, including identification of candidates, localization of the seizure focus, and surgical techniques.

The extent to which white matter lesions affect brain function in elderly individuals has important implications for the development of drugs to treat cognitive impairment and dementia. In this article, Frisoni et al. argue that white matter lesions can contribute to cognitive impairment in elderly individuals, although their effects are minor when compared with those of other causes of cognitive deterioration, such as Alzheimer's disease.

Migraine is a common disabling brain disorder that—considering its clinical and economic impact—is understudied and in need of additional management options. In this Review, Peter Goadsby outlines new pharmaceutical and device-based approaches to migraine treatment by describing their potential mechanisms of action and the clinical data that are currently available.

Surgery is becoming a viable treatment option for an increasing proportion of patients with low-grade gliomas, but there is a lack of class I evidence to support its efficacy. In this Review, Pouratianet al. critically analyze the utility of surgery in low-grade glioma. They highlight recent technological advances that have made this approach safer and more accessible, and consider the challenges involved in designing trials to assess the extent to which aggressive resection improves prognosis.

Prematurely born infants are at high risk of brain injury, but although structural and volumetric alterations often persist into later life, there is strong evidence of recovery from cognitive impairments associated with preterm birth. In this Review, Ment and Constable discuss how functional MRI techniques are providing important insights into the adaptive mechanisms of the developing preterm brain, including the engagement of alternative neural networks for language and memory.