Review Articles in 2012

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.

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.

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.

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.

In recent years, the central roles of neuronal and axonal damage, as well as axon–glial and axon–myelin interactions, in the pathogenesis and progression of multiple sclerosis (MS) have become increasingly apparent. Franklin et al. review advances in our understanding of the molecular mechanisms underlying these MS-related events, and discuss approaches towards axonal neuroprotection and repair, particularly through the regenerative process remyelination.

In this Review, von Geldern and Mowry discuss the potential effects of vitamin D and other dietary components on the disease course of multiple sclerosis (MS). Numerous studies have looked at the effects of nutrition on relapse rate and/or disease progression in this condition, and here the authors provide an overview of and a biological rationale for nutritional therapy in MS.

Over the past few decades, considerable progress has been made in understanding the mechanisms underlying the relapsing–remitting stage of multiple sclerosis (MS), but the disease processes that drive progressive MS remain largely unresolved. In this Review, Lassmann and colleagues explore the current state of knowledge on the pathophysiology of progressive MS, and present a pathogenetic concept for this phase of the disease that involves oxidative stress and mitochondrial injury.

Despite widespread damage associated with multiple sclerosis (MS) pathology, recovery of function can occur, driven by adaptive plasticity in brain networks. Tomassini et al. review the mechanisms underlying functional recovery in MS, and discuss interventions that might promote this process. Methodological considerations for imaging neuroplasticity using functional MRI are also highlighted.

Sepsis-associated encephalopathy (SAE) is a clinical syndrome that is associated with diffuse brain dysfunction and is secondary to infection in the body. Severity of SAE ranges from mild delirium to deep coma, and mortality reaches almost 70% in severe cases. In this Review, Gofton and Young provide an overview of the epidemiology and clinical presentation of SAE. They discuss current evidence relating to the pathophysiology and prognosis of SAE, and present a diagnostic approach and management strategy for patients with the disease.

This Review discusses the concept of pharmacoresistant epilepsy and describes the identification and management of this frequently misdiagnosed condition, focusing on the underutilized role of surgical treatment. Wiebe and Jette present robust evidence of the safety and efficacy of epilepsy surgery in patients with confirmed pharmacoresistant epilepsy, and suggest that epilepsy surgery should be considered promptly for these individuals.

Cranial radiation therapy (CRT) is commonly used to treat brain tumours but, in paediatric patients, this therapeutic strategy can lead to subsequent neurocognitive impairment. Padovani et al. discuss both the mechanisms underlying the effect of CRT on cognitive function and factors that can affect outcome. New approaches to correct or avoid CRT-induced neurotoxicity are also considered.

Treatments for the hereditary optic neuropathies, including Leber hereditary optic neuropathy and dominant optic atrophy, are limited. In this Review, Nancy Newman summarizes the natural history of hereditary optic neuropathies, and the role of mitochondrial dysfunction in their pathogenesis. She highlights recent advances in the treatment of these disorders, and indicates how insights into the hereditary optic neuropathies could have therapeutic implications for other disorders of presumed mitochondrial dysfunction.

Around half of all stroke survivors exhibit spatial neglect—a failure to report, respond to or orientate to contralesional stimuli. Current therapeutic approaches for spatial neglect focus largely on visual perceptual processing, but many patients respond poorly to such approaches because their main impairments lie in spatial motor 'aiming' function. Here, Barrett et al. highlight a promising alternative approach—prism adaptation treatment—that specifically targets spatial motor deficits.

Gene expression profiling (GEP) has advanced considerably in the past 5 years, and has been used to study differential gene expression associated with various neurological disorders. In their Review, Shaw and colleagues review recent GEP studies in amyotrophic lateral sclerosis, Parkinson disease and Alzheimer disease. The findings have highlighted involvement of shared and distinct pathways across diseases, and point to possible biomarkers and therapeutic targets that could improve future diagnosis and treatment.

EEG source imaging (ESI) is a technique designed to predict the source of a given field potential obtained using EEG. Kaiboriboonet al.describe the principles and technical aspects underlying ESI in epilepsy. They discuss the practicalities and pitfalls of ESI in the clinical setting, specifically for epileptic source localization and identification of the eloquent cortex—two important considerations when planning resective surgery in patients with refractory epilepsy.