Reviews & Analysis

Analysis of two recombinant tissue plasminogen activator (rtPA) trials by means of the disability-adjusted life year metric has provided readily understandable data on the benefits of rtPA therapy in acute ischemic stroke. Approximately one-third of patients treated with rtPA could gain more than 4 years of healthy life, which is twice that previously estimated.

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.

Activated microglia are a feature of many neurodegenerative disorders, including amyotrophic lateral sclerosis and Alzheimer disease. Conflicting results exist, however, for the effectiveness of anti-inflammatory drugs in such conditions. In this article, Schwartz and Shechter propose a model that describes the complexities of the immune response in neurodegenerative diseases and offer an explanation for why such drugs have so far yielded inconsistent data in this setting.

The burden of cerebrovascular disease is thought to be greater than current official estimates. A new systematic review shows that a history of stroke is associated with an increased risk of incident dementia in the elderly. The findings also highlight the confusion in the classification of dementia and the need for more recognition of vascular-related cognitive disorders.

Classification of glioblastomas into various molecular entities is required for the successful application of targeted therapeutics and personalized cancer therapy. Analyses of gene expression, genomic mutations and DNA copy number identified four molecular subtypes among histopathologically indistinguishable glioblastomas. This classification suggests the existence of distinct paths of tumor cell origin and variation in therapeutic sensitivity.

Two genome-wide association studies have independently identified genetic risk factors for Parkinson disease (PD). One study, conducted in individuals of European ancestry, provides further evidence for an association between PD risk and the genes SNCA and MAPT. The other study, conducted in a Japanese series, identified two novel loci that are associated with PD risk.

The dramatic increase in survival of extremely premature infants has been associated with a growing population of individuals with neurodevelopmental disabilities. To date, clinical trials of neuroprotective agents in preterm infants have been limited, but new data suggest that erythropoietin might have important neuroprotective effects in these vulnerable infants.

The role of hyperlipidemia as a risk factor for stroke is unclear. A new retrospective study has examined the relationship between a history of hyperlipidemia and MRI-defined white matter hyperintensities in patients with acute ischemic stroke. The results indicate that hyperlipidemia might have a protective role against cerebral small-vessel disease.

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.

Behavioral variant frontotemporal dementia (bvFTD) is characterized by a decline in social skills, emotions, personal conduct and self-awareness, that is indicative of frontal lobe degeneration. Facundo Manes and colleagues report on a case of a patient presenting with pathological gambling who went on to develop the typical syndrome of bvFTD. The authors discuss the importance of recognizing symptoms of bvFTD and raise issues about the legal implications of the diagnosis.

Evidence suggests that both anxiety and depression might have pathophysiological links with Parkinson disease (PD), as these mood disorders are more prevalent in individuals with PD than in patients with other chronic conditions. A new study reports that depression and anxiety are associated with different patterns of PD-related factors, suggesting divergence between the underlying mechanisms.

Surgical revascularization has been accepted as an effective therapeutic option to improve cerebral hemodynamics, reduce further cerebrovascular events and improve long-term outcomes in pediatric moyamoya disease. A large clinical study now provides us with additional meaningful information on the benefits of surgical revascularization for patients with this condition.

The neural mechanisms of many symptoms associated with migraine have yet to be elucidated. New research suggests that a non-image-forming retinal pathway and signals from the dura mater contribute to photophobia in patients with migraine. More research is needed to understand the mechanisms behind other migraine-associated symptoms such as nausea and osmophobia.

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.