Review Articles in 2010

The adipocyte-derived hormone leptin provides a link between metabolic status and the immune system, and has been implicated in the pathogenesis of autoimmune disorders such as multiple sclerosis (MS). Matarese et al. review clinical and molecular evidence for an association between leptin and MS disease activity, and consider the prospects for metabolic and nutritional interventions in the treatment of this condition.

Neuromyelitis optica is a CNS inflammatory disorder that predominantly affects the optic nerves and spinal cord. Jarius and Wildemann review the latest experimental and clinical evidence that supports a direct role for antibodies to aquaporin-4—the most abundant water channel in the brain—in the immunopathogenesis of this condition. The authors also evaluate the range of diagnostic tests that are currently available for the detection of these antibodies.

Many individuals who survive traumatic brain injury (TBI) experience long-term complications. The prevention and management of such complications, however, remain challenging goals for clinicians. Here, Shlosberg and colleague examine the role of blood–brain barrier (BBB) breakdown in the pathophysiology of TBI, particularly in the development of delayed TBI-related conditions. The authors also discuss novel BBB-targeted therapeutic strategies that might be explored to counter or prevent long-term complications in patients.

Only moderately effective therapies are currently available for the treatment of multiple sclerosis (MS). New treatments for MS that have neuroprotective properties as well as anti-inflammatory effects are needed. Fingolimod could be one such potential treatment. In this article, Aktas et al. examine the underlying biological actions of this prospective new therapy, review the data from phase II and phase III oral fingolimod clinical trials and provide an update on the emerging field of sphingosine-1-phosphate receptor-mediated therapies for MS.

Stem cell therapy has the potential to provide a valuable treatment approach for spinal cord injury, but no consensus yet exists regarding which type of stem cell is likely to be most effective in the clinical setting. In this article, Sahni and Kessler review the various stem cell strategies that have been tested in animal models for the treatment of spinal cord injury, and discuss ongoing clinical trials and future prospects for stem cell therapy in humans.

Restless legs syndrome (RLS) is a somatosensory network disorder, a key feature of which is an overwhelming urge to move the legs. In this article, Trenkwalder and Paulus review the state of knowledge regarding the pathophysiology of RLS, including the proposed roles of the dopamine and iron systems, and discuss current approaches to the diagnosis and treatment of this condition.

The success of future preventative treatments for dementia might rely on early and accurate identification of individuals who have a high risk of developing this condition. Here, Stephan et al. examine models of dementia risk prediction that have been tested in population-based samples. The authors discuss the predictive utility of both mild cognitive impairment criteria, and population screening models that combine cognitive deficits with other known dementia risk factors.

The brains of preterm infants are highly vulnerable to injury caused by hypoxic–ischemic events and inflammation, which can have deleterious consequences both acutely and later in life. In this article, Deng reviews evidence regarding the neurobiology of injury to immature white matter, including the roles of activated microglia and astrogliosis, and discusses potential therapies for this condition.

The development of interventions to slow or prevent the progression of Parkinson disease (PD) will depend on a clearer understanding of the etiology and pathophysiology of the disease. Schapira and Tolosa describe the biochemical events and pathways that are thought to comprise the molecular prodrome of PD and consider how these events might relate to the pathological changes and clinical features that characterize the early phase of PD.

Stem cell-based therapies have the potential to revolutionize the treatment of multiple sclerosis (MS). In this Review, Martino et al. provide an overview of the current knowledge relating to the potential use of transplanted mesenchymal stem cells and neural stem/precursor cells in the treatment of MS.

Treatments for myelin disorders, such as multiple sclerosis, are largely confined to anti-inflammatory drugs, which often show limited effectiveness in only subgroups of patients. Combination therapies that target both inflammation and other processes, such as remyelination, might be of benefit in such disorders. In this article, Taveggia et al. provide an overview of the signaling pathways that regulate myelination and highlight how targeting such pathways might promote remyelination.

Since the introduction of electroconvulsive therapy in the 1930s, considerable progress has been made in the development and refinement of brain stimulation techniques to treat psychiatric illness. The ultimate goal is to achieve clinical efficacy while minimizing cognitive adverse effects, and Hoy and Fitzgerald consider the extent to which various noninvasive and invasive brain stimulation techniques fulfill these requirements.

Most cases of stroke occur in the elderly, and stroke morbidity and mortality rates rise with increasing age. In this Review, Chen and colleagues examine the relationship between age and ischemic stroke, including discussion of the age-related changes that make elderly people particularly vulnerable to stroke and the factors that might be responsible for the poor outcomes observed in this patient group.

TAR DNA-binding protein 43 (TDP-43) inclusions are the main histopathological feature of amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar degeneration (FTLD). In this article, Chen-Plotkinet al. examine the TDP-43 pathology found in these and other neurodegenerative diseases. They also argue for ALS and FTLD with TDP-43 inclusions to be considered as two ends of a continuum of disease that is characterized by TDP-43-mediated neurodegeneration.

Microglia rapidly adopt an activated phenotype in response to brain injury and disease, which suggests that they could act as diagnostic markers of neurodegenerative disease onset or progression. In this article, Perry et al. review the relationship between activated microglia and neurodegenerative diseases and discuss the interactions between microglial phenotype, systemic inflammation and neurodegenerative disease progression.

Blindness in adults is frequently caused by acquired optic neuropathies, which can have vascular, inflammatory, toxic, nutritional, compressive, infiltrative or traumatic etiologies. Diagnosis of these neuropathies depends on accurate and precise examination of optic nerve head morphology. O' Neill et al. describe the morphological features of the optic nerve head in the various acquired optic neuropathies and explore the roles of new imaging modalities in the assessment of these disease entities.

Aphasia is a disorder caused by damage to the brain regions that support the ability to comprehend and produce speech, and is a common occurrence after stroke. At present, clinicians cannot reliably predict the extent to which a patient with stroke is likely to recover from aphasia. In this article, Priceet al. introduce PLORAS (Predicting Language Outcome and Recovery After Stroke), a new data-led system that is designed to predict language outcome on the basis of lesion site.

Epidemiological data indicate that genetic and environmental factors interact to determine an individual's risk of developing multiple sclerosis (MS). Handel et al. examine the key periods of life during which the environment might contribute to MS susceptibility, focusing on three putative MS risk factors: sun exposure (and its relationship with vitamin D levels), Epstein–Barr virus infection, and smoking.

The early detection of Alzheimer disease might be critical to the effectiveness of disease-modifying drugs, when such therapies become available. In this Review, Blennowet al. examine the use of cerebrospinal fluid and plasma biomarkers in the early diagnosis of this neurodegenerative disorder. The authors also explore roles for cerebrospinal fluid biomarkers in Alzheimer disease clinical trials.

Individuals with acute ischemic stroke are frequently shown to have hyperglycemia when admitted to hospital and elevated levels of blood glucose are associated with a poor prognosis. Tight glycemic control (TGC) might be an effective treatment for hyperglycemia in patients with acute ischemic stroke; however, successful and safe provision of TGC is a challenging task. This Review examines the evidence linking hyperglycemia to unfavorable prognoses in patients with acute stroke, provides a systematic review of the literature concerning TGC treatment after stroke and proposes directions on how to treat hyperglycemia in patients with stroke.