Reviews & Analysis

The clinical role of acetylcholinesterase inhibitors in the treatment of Alzheimer's disease remains unresolved. This Viewpoint examines the evidence from clinical trials and argues for a conservative approach to the use of these drugs in patients with dementia.

A number of epidemiological studies have provided evidence for a link between type 2 diabetes and Alzheimer's disease. In this review, Mary Haan weighs up this evidence, considers some potential biological mechanisms that might underlie the link, and discusses how targeting the risk factors for type 2 diabetes might also help in reducing the incidence of Alzheimer's disease.

The postgenomic era has seen important advances in the ability to perform large-scale analysis, using microarrays, of the genome at the level of gene sequence, gene copy number and messenger RNA transcript expression. In this review, Coppola and Geschwind discuss how microarray technology is being used to study of the genetics and pathogenesis of neurological disorders, and how it might be used in the future for patient diagnosis and classification into treatment groups.

Parkinson disease has traditionally been perceived as a non-hereditary condition, but in recent years, the identification of heritable forms of the disease linked to mutations in single genes has challenged this view. This review highlights recent progress in establishing the neurogenetic basis of Parkinson disease, and considers scenarios in which genetic testing for this condition might be warranted.

Procedures for handling incidental findings in brain imaging research vary widely. Through considering the principles that govern how incidental findings should be dealt with, the author highlights concepts and strategies to help guide researchers and practitioners through the choices they must make.

Neuropathic pain is caused by damage to the parts of the nervous system that normally signal pain. Attempts to classify neuropathic pain patients on the basis of disease etiology or lesion topography have met with limited success, and in this review Ralf Baron presents an alternative system based on molecular mechanisms. He discusses how this approach might lead to the development of more rational treatments for neuropathic pain.

Even in cases of well-controlled type 1 diabetes, cerebral glucose levels are frequently abnormal, and this is thought to have an impact on brain development and function. This article reviews the emerging literature that documents pathophysiological CNS changes and neurocognitive deficits in adults and children with type 1 diabetes, and discusses the implications for the clinical management of these patients.

Skeletal system metastases are the third most common type of metastases in patients with cancer, and metastatic epidural spinal cord compression (MESCC) is estimated to occur in 5–10% of all cancer patients. In this review, Withamet al. discuss current strategies for the clinical management of MESCC, including radiotherapeutic and surgical approaches, and they also consider some emerging treatment options.

In this issue, Ralf Baron has described the molecular mechanisms that underlie neuropathic pain, but how close are we to translating these mechanisms into viable treatment strategies in the clinic? In this accompanying review, Nanna Finnerup and Troels Jensen address this question through a critical evaluation of the mechanism-based approach to neuropathic pain classification.

This Viewpoint examines the management options for arteriovenous malformations and the grading scales that can be used to guide treatment decisions. The authors consider the natural history of unruptured arteriovenous malformations and evaluate the risks associated with available treatments.

High levels of plasma homocysteine have been linked with stroke, and it has been proposed that stroke risk might be reduced by lowering homocysteine levels using folicacid based multivitamin treatment. There is insufficient evidence, however, to indicate that homocysteine is a modifiable risk factor for stroke, and, given the costs and potential risks of vitamin therapy, it cannot currently be recommended as a standard approach.

The Charcot–Marie–Tooth (CMT) neuropathies fall into two main groups: the demyelinating (CMT1) forms, in which nerve conduction velocities are reduced, and the axonal (CMT2) forms, in which nerve conduction velocities are preserved but conduction amplitudes are decreased. In this article, Züchner and Vance review recent advances in our understanding of the genetic and molecular mechanisms that underlie CMT2.

Interferons are naturally occurring proteins with antiviral, antiproliferative, antineoplastic and immunomodulatory actions. This article reviews the findings of a series of clinical trials conducted between 1987 and 1997, which showed that interferon-β has beneficial effects on relapses and short-term disability in patients with multiple sclerosis.

Currently, there is considerable scientific interest in modes of imaging that rely on the metabolic characteristics of tissues. Metabolic imaging is emerging as a promising diagnostic tool for the evaluation of cerebral gliomas, although it remains to be seen whether treatment decisions based on this approach will produce significant improvements in outcome.

It is estimated that epilepsy affects up to 1% of the world's population, and although many patients derive considerable benefits from antiepileptic drugs or resective surgery, new therapeutic approaches are still needed. In this Viewpoint, William Theodore assesses the potential of techniques that involve direct or indirect electrical stimulation of the epileptic focus.

Despite advances in surgery, radiotherapy and chemotherapy, the median survival for patients with glioblastoma—the most common primary brain tumor in adults—has changed little in 40 years. A recent trial, however, has shown that administration of the DNA methylating agent temozolamide during and after radiotherapy can prolong survival in patients with newly diagnosed glioblastomas.

Statins are best known for their cholesterol-lowering effects, but they also have immunomodulatory properties that might be exploited to treat neuroinflammatory disorders, such as multiple sclerosis. This review describes the molecular and cellular mechanisms that are thought to underlie the immunomodulatory effects, and discusses the results of initial clinical trials of statins in patients with multiple sclerosis.