Volume 9 Issue 1, January 2013

Anaplastic oligodendroglial tumours are chemosensitive tumours—a fact that has been known for almost 25 years. The role and optimal timing of chemotherapy, however, has remained a subject of debate. Long-term results of two phase III trials now show that, in patients with 1p19q-codeleted tumours, early chemotherapy increases overall survival.

Several oral drugs have been developed in recent years for treatment of relapsing–remitting multiple sclerosis. Two large phase III trials have now clearly demonstrated the clinical efficacy and good safety profile of oral dimethyl fumarate (BG12)—an anti-inflammatory and cytoprotective agent—in patients with this disease.

Differential diagnosis of Creutzfeldt–Jakob disease (CJD) versus other—sometimes treatable—neurological disorders is challenging, owing in part to uncertainty about the utility of recommended diagnostic tools. Two recent studies have addressed the reliability of cerebrospinal fluid biomarkers in identification of patients with sporadic CJD among clinically suspected cases.

In 1912, Fritz Heinrich Lewy identified the intracellular inclusions that are characteristic of Parkinson disease (PD). Here, Goedert and colleagues present an overview of Lewy's life, including the events leading up to the discovery of the inclusion bodies that now bear his name. They go on to discuss the central role of Lewy pathology in PD and other neurodegenerative disorders, and the research that has elucidated the mechanisms through which α-synuclein aggregation causes neuronal dysfunction and death.

Drug development efforts for late-onset Alzheimer disease (AD) have met with disappointing results. Krstic and Knuesel argue for a re-evaluation of pathological mechanisms underlying the disease, with a shift of focus away from amyloid-β as the key therapeutic target. Through integration of their own research with the wider literature, they present a model that places inflammation and impairments in axonal functions and integrity at the heart of AD pathology.

Multiple sclerosis (MS) is a disease with both inflammatory and neurodegenerative components. In this Review, the authors discuss the potential roles of epigenetic changes in modulating MS disease progression and mediating the effects of environmental risk factors. They also discuss current knowledge of the pathophysiology of MS, including immune cell differentiation and epigenetic changes in relapsing–remitting and progressive MS.

The eye is an extension of the CNS in terms of its development and anatomy, and in terms of its dialogue with the immune system. Many neurodegenerative disorders of the brain and spinal cord have manifestations in the eye, which are often evident before the emergence of clinical neurological symptoms. London et al. highlight how investigation of the eye represents a noninvasive approach to the detection and diagnosis of neurodegenerative disorders, and discuss how eye research could provide a valuable model to study CNS disorders.

Pathological changes underlying Alzheimer disease (AD) begin more than 10 years before clinical presentation, and the need for early therapeutic intervention is becoming increasingly recognized. Reisa Sperling and colleagues consider challenges to such an approach—including the difficulty of defining preclinical AD, and ethical issues associated with disclosing information on AD biomarker status to healthy individuals—and discuss possible ways to overcome these hurdles.