Reviews & Analysis

Recent data show that MRI at term-equivalent age can predict neurodevelopmental outcomes in infants born far before term. So should cranial MRI screening replace cranial ultrasound in preterm babies? The authors of this Viewpoint weigh up the options.

In this Review, Sacktor et al. summarize our current understanding of HIV-associated cognitive impairment in resource-limited settings, focusing specifically on the countries of sub-Saharan Africa. They also consider the potential impact of HIV-1 clade diversity on HIV-associated neurological disease.

Charcot–Marie–Tooth disease is the most common inherited disease of the PNS. This Review summarizes our current understanding of the genetic and molecular mechanisms that underlie the demyelinating forms of Charcot–Marie–Tooth disease. The authors also discuss how knowledge of these mechanisms is guiding the development of strategies to diagnose and treat these conditions in the clinic.

The emerging field of neuroprosthetics is focused on the development of therapeutic interventions that restore lost neural function by stimulating sensory or motor pathways, or by harnessing activity recorded from remnant neural pathways to control an external device. As Richard Normann discusses in this Review, penetrating microelectrode arrays are providing unprecedented selective access to the neurons of the CNS and PNS, and are likely to form the basis for new therapies for disorders of the nervous system.

The rostral ventrolateral medulla has a major role in the regulation of sympathetic and cardiovascular activities. It has been suggested that neurovascular compression of this area might be causally linked to essential hypertension. In this Viewpoint, the authors highlight the pertinent issues and the clinical relevance of this important debate.

Last year's Nobel Prize in Physiology or Medicine was won by Andrew Fire and Craig Mello for their discovery of RNA interference, an evolutionarily conserved cellular pathway that regulates endogenous gene expression. In this Review, Gonzalez and Paulson discuss how RNA interference is being exploited experimentally to suppress the expression of dominantly acting genes that cause incurable neurodegenerative disorders, and highlight the questions that need to be answered before human clinical trials of this technology can commence.

Alzheimer's disease is characterized pathologically by the deposition in the brain of amyloid-β peptides generated through proteolysis of amyloid precursor protein (APP). In this article, Cheng et al. review evidence that amyloidogenic processing of APP takes place predominantly in cholesterol-rich membrane microdomains known as lipid rafts. They also discuss potential new therapeutic strategies based on the targeting of APP processing in lipid rafts.

The use of brain stimulation for the treatment of neurological diseases such as chronic pain, Parkinson's disease, stroke and epilepsy has attracted growing attention. In this article, Fregni and Pascual-Leone review the recent literature regarding the use of two noninvasive brain stimulation techniques: repetitive transcranial magnetic stimulation and transcranial direct current stimulation. The authors discuss the underlying principles and present examples illustrating the therapeutic potential of these two techniques.

Restless legs syndrome has become increasingly prominent in the clinical literature in recent years, but the prevalence of this condition is still unknown. In this Viewpoint, Claudia Trenkwalder highlights the debate regarding whether restless legs syndrome is overdiagnosed or underdiagnosed, and she considers possible explanations for the differences in opinion within the neurology field.

A recent study has shown that brain research is poorly funded compared with research in fields such as cancer and heart disease. In this Viewpoint, Jes Olesen discusses possible reasons for this discrepancy, and describes how the European Brain Council is bringing together basic neuroscientists, clinical neurologists and patient organizations to promote brain research and to facilitate the translation of new advances into real benefits for patients.

Baló's concentric sclerosis (BCS) is a demyelinating disorder characterized by white matter lesions consisting of rings of demyelination alternating with rings of relatively intact myelin. In this Review, Mowryet al.discuss how advanced neuroimaging techniques have contributed to our understanding of the pathogenesis of BCS, as well as enabling clinicians to distinguish BCS from other demyelinating disorders such as multiple sclerosis. The authors explore these themes further in a Case Study in this issue.

Diabetic neuropathy—the most common neuropathy in industrialized countries—encompasses a broad range of clinical manifestations. In this Review, Gérard Said discusses the clinical, pathological and therapeutic aspects of various forms of diabetic neuropathy, including length-dependent diabetic polyneuropathy and focal diabetic neuropathies. The author also addresses the diagnosis of nondiabetic neuropathies in patients with diabetes.

Around a third of patients with epilepsy have refractory epilepsy; that is, they continue to have seizures despite trying a range of antiepileptic drugs. Recent basic research has explored the underlying causes of refractory epilepsy, and in this article Sanjay Sisodiya discusses the two main hypotheses that have emerged from these studies. He also considers how knowledge of the molecular basis of refractoriness might guide the development of new therapies.

In this Viewpoint, Williamsonet al. highlight the distinction between genetic research and clinical testing in Alzheimer's disease. They consider how neurologists can bridge the gap between scientific advances and patient management, helping patients and their families to navigate this complex territory.

Despite encouraging preclinical results, clinical trials of neuroprotective agents for Parkinson's disease have failed to show consistent clinical benefit. In this Viewpoint article, Karl Kieburtz and Bernard Ravina analyze the reasons behind this lack of success and draw conclusions on how to move forward.

Cerebral vasospasm is the classic cause of delayed neurological deterioration after subarachnoid hemorrhage (SAH). Surprisingly, however, patient outcome after SAH was not improved in recent trials of the endothelin antagonist clazosentan, which prevents vasospasm. In light of this result, Macdonald et al. highlight the need for reconsideration of the pathophysiology of SAH.