Reviews & Analysis

Hypertension is highly prevalent, particularly in individuals over 60 years of age, and constitutes a major risk factor for stroke and dementia. Antihypertensive therapy in elderly individuals has, however, been limited owing to concerns over adverse effects of such therapies. In this Perspectives article, Sörös et al. emphasize that treatment of hypertension can markedly reduce stroke and dementia risk, and argue that antihypertensive therapy should be considered in all patients, irrespective of age.

Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of misfolded prion protein. The time from infection to onset of disease symptoms can be decades, and the public health risk from infective prions is considerable. In this Review the authors discuss current research into passive and active immunization strategies against prion diseases, and the potential for effective therapy.

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.

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.

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.

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.

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.

Idiopathic intracranial hypertension (IIH) is a rare disorder that is most prevalent in obese populations and can occur at any age. This Review provides an update on the aetiology, pathophysiology and treatment of IIH. The authors discuss challenges to making a diagnosis, potential disease mechanisms, and treatment options for patients.

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.

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.

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.

Controversy exists over the best treatment option in elderly patients with glioblastoma. A recent study in glioblastoma patients who were over 60 years of age found improved survival rates with temozolomide chemotherapy compared with radiotherapy, and confirmed the validity of MGMT methylation status for prediction of benefit from temozolomide treatment.

Three recent phase III trials have shown that adjunctive treatment with perampanel—a first-in-class, noncompetitive AMPA antagonist—decreases seizure frequency in patients with refractory focal epilepsy. Although the introduction of perampanel offers more treatment choice for epilepsy, whether it brings urgently needed clinical benefit over existing drugs remains to be addressed.

Nearly 40% of ischaemic strokes remain cryptogenic when no clear aetiology is identified after a thorough initial investigation. Two recent articles in Stroke described extended arrhythmia monitoring modalities to reveal paroxysmal atrial fibrillation in patients with ischaemic stroke, with implications for decisions regarding anticoagulation.

Owing to recent advances in brain–machine interfaces and electrical stimulation of the spinal cord, restoration motor function in patients with spinal cord injury (SCI) has become a reality. Jackson and Zimmerman review the mechanisms underlying closed-loop interfaces—in which electrical stimulation is driven by neural output—as prostheses, and propose that such devices enhance neural plasticity, thereby providing long-term therapeutic benefits to patients with SCI.

New EFNS–ENS guidelines provide a broad and comprehensive overview of the literature and key recommendations regarding treatment and diagnosis across a vast range of conditions associated with dementia, with the exception of Alzheimer disease, which was deliberately excluded. Although excellent, the breadth and brevity of the guidelines lead to some important omissions.

In a recent trial investigating the effectiveness of speech and language therapy versus a control intervention in poststroke aphasia, patient outcome improved equally in both groups. However, flaws in the study relating to design of the control intervention, inadequate therapy 'dose', and the interpretation of null results should be highlighted.

The neurovascular unit is a key concept in stroke medicine that for many years has been defined as the endothelial cells, neurons and glia surrounding cerebral capillaries. In this Perspectives article, the authors expand this concept to encompass more-distant circulation, smooth muscle cells and perivascular innervation. This 'neural vascular network' in turn points to new strategies for stroke therapy.

Strong evidence supports the importance of genetic factors in the development of multiple sclerosis (MS), but environmental factors also have a major role. Ascherio et al. review the evidence for such factors, with a focus on three main aspects: infection with Epstein–Barr virus, vitamin D nutrition, and cigarette smoking. They discuss how these processes might influence the initiation of MS, the potential for therapeutic approaches that target these risk factors, and how lifestyle modification could aid in MS prevention.

Increasing evidence supports a role for B cells and antibodies in the pathogenesis of multiple sclerosis (MS). Here, Meinl and colleagues discuss the proinflammatory contribution of B-cell signalling in MS, and consider potential targets of autoantibodies. The B-cell response to various MS therapies is also summarized.