Reviews & Analysis

Inborn errors of metabolism account for around a third of all genetic diseases. They can affect many organs, but in most cases they involve the nervous system. This Review focuses on treatable inborn errors of metabolism that can be diagnosed in a neurology department, and proposes guidelines to help neurologists to avoid overlooking treatable metabolic diseases.

Children with sickle cell disease present with a variety of neurological syndromes, including ischemic and hemorrhagic stroke. In this Review, Fenella Kirkham describes the clinical and pathological features of stroke in individuals with sickle cell disease, and considers strategies for prevention and management of stroke in this patient population.

Nanotechnology is often hailed as a revolutionary technology. In this Viewpoint article, Gabriel Silva presents emerging nanotechnology applications directed towards neurological disorders and assesses their potential to provide patients with novel and advanced therapeutic choices.

Stenting is being used increasingly for the treatment of carotid artery stenosis, but it is still unknown whether it is as safe and successful as carotid endarterectomy—the standard treatment for symptomatic patients with more than 50% carotid stenosis. This Review summarizes current knowledge on the effectiveness of both procedures, and provides an updated meta-analysis based on data from randomized trials.

Melatonin has been used successfully to treat insomnia, but has not received regulatory approval by the FDA because it can be sold freely as a food supplement. This has prompted a search by pharmaceutical companies for patentable melatonin receptor ligands, and the melatonin receptor agonist ramelteon has received particular attention. This Review describes the pharmacology and metabolism of ramelteon, assesses evidence from animal models and clinical studies that supports its efficacy in treating insomnia, and discusses its possible mechanism of action.

In recent years, considerable progress has been made towards understanding the mechanisms that underlie autoimmune inflammatory diseases of the PNS, such as Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy. As Meyer zu Hörste et al. discuss in this Review, many promising therapeutic approaches for these conditions have been established in animal models, but attempts to transfer this knowledge to the clinic have met with limited success to date.

In recent years, we have witnessed an alarming worldwide shortage of intravenous immunoglobulin, an agent that is commonly used to treat various autoimmune and systemic inflammatory diseases, many of which affect the nervous system. In this Viewpoint, Bayryet al.explain the reasons for this shortage, and propose some potential solutions to the problem.

Numerous lines of evidence from animal studies indicate that transplants of olfactory ensheathing cells—glial cells derived from the olfactory system—can promote functional recovery in the injured spinal cord. In this Review, Barnett and Riddell analyze this evidence and examine the mechanisms by which repair might be achieved, as well as assessing the prospects for translating this approach into the clinic.

Following the discovery that the brain is strikingly susceptible to oxidative DNA damage, considerable attention has been focused on improving our knowledge of the brain's DNA repair pathways and genomic stability. In this article, Kalluri Subba Rao reviews the current state of knowledge regarding neurological diseases that have an etiological link with DNA repair defects, discussing the relationship between the neurological phenotype and the DNA repair pathway that is compromised.

X-linked adrenoleukodystrophy is a genetic neurodegenerative disorder that is characterized biochemically by abnormal accumulation of very long chain fatty acids in all tissues of the body. In this Review, Moseret al.describe the biochemical, genetic and clinical features of this disorder, and discuss new approaches to its diagnosis and treatment, including newborn screening and the use of Lorenzo's oil.

Ronald Petersen developed the concept of mild cognitive impairment (MCI) in the late 1990s. The concept has since been expanded to include several subtypes, with amnestic MCI being recognized as a risk state for Alzheimer's disease. This Viewpoint highlights the benefits of retaining the MCI classification, both from a research and from a clinical point of view.

Mild cognitive impairment has become a popular concept for classifying the boundaries between normal aging and dementia, but is it a legitimate diagnosis? In this Viewpoint article, Peter Whitehouse argues that the concept of mild cognitive impairment is fundamentally flawed and driven to a large extent by stakeholder interests.

Most human herpesviruses are neurotropic and have the capability to cause serious acute and chronic neurological diseases of the nervous system. In this article, Gilden et al. review current knowledge regarding the clinical features, pathogenesis and treatment of the various neurological complications that can result from herpesvirus infections.

Fabry's disease is an X-linked lysosomal storage disorder, the primary pathology of which is accumulation of glycosphingolipids in cells throughout the body, including the nervous system. Neurological symptoms, which include pain, abnormal sensations and stroke, are evident early in the disease course. In this Review, Møller and Jensen highlight the importance of recognizing these symptoms in order to ensure a rapid diagnosis.

In this Viewpoint article, Alastair Buchan and James Kennedy evaluate emerging options for the treatment of acute ischemic stroke and discuss the difficulties associated with choosing the patients who might benefit most from them.

Primary CNS lymphoma, an extranodal non-Hodgkin's lymphoma that invades the nervous system, accounts for around 3% of all primary brain tumors. In this Review, Hochberg et al. highlight recent advances in our understanding of the pathogenesis of primary CNS lymphoma, and they discuss current approaches to the diagnosis and therapy of this condition.