Hot Topics at the Podium
Every year, one of the most interesting sessions at the meeting of the American Academy of Neurology is the “Hot Topics” plenary. For this session, the Science Committee selects 4 researchers whose work bridges the laboratory, clinical, and public health spheres, and has a major impact on how we study, diagnose, conceptualize, or treat neurologic conditions. The variety of topics discussed by the speakers only highlights the richness of the field of neurology.
Chronic Traumatic Encephalopathy
Traumatic brain injury is among the major contributors to the global neurologic burden of disease. Some patients with mild to moderate brain injury recover, others develop chronic stable symptoms (postconcussion syndrome), and still others have the progressive behavioral and cognitive changes of chronic traumatic encephalopathy (CTE) that lead to dementia. Recent research has shed some light on the pathologic substrate of these phenotypic manifestations, but as Dennis Dickson, MD, Professor of Laboratory Medicine & Pathology at the Mayo Clinic in Jacksonville, Florida, reminded us in his talk, this field of research is still in its infancy.
The prevalence of CTE is unknown, but according to data from the Mayo brain bank, Dr. Dickson estimates that it could be as high as 20% in male athletes involved in contact sports. CTE is a chronic and progressive disorder characterized neuropathologically by the accumulation of hyperphosphorylated tau. In the earliest stages of the disease, tau deposits are found in the deep layers of the sulci of the frontal neocortex, but as clinical and pathologic severity increase, neurofibrillary tangles involve other brain areas, including the insula, temporal lobe, amygdala, hippocampus, and subcortical structures.
The clinical manifestations of CTE are variable, but Ann McKee and her group at Boston University have identified 2 phenotypes: The first is characterized by early behavioral and mood changes, and the second by prominent cognitive impairment that progresses to dementia. It is unclear what factors determine the phenotype in each individual.
The lack of definitive neuropsychological, clinical, and neuropathologic criteria hampers developments in the field. Several groups are working to develop serum, cerebrospinal fluid, and imaging biomarkers to study CTE in vivo. Techniques under study include diffusion tensor imaging to evaluate changes in the white matter, functional MRI to assess changes in neuronal networks, and tau PET to identify molecular markers that will allow localization and identification of the spread of the pathology and differentiation of CTE from other tauopathies.
In 2010, researchers at Boston University reported an intriguing association between CTE and amyotrophic lateral sclerosis (ALS). Using samples from the Mayo brain bank, Dr. Dickson found that 5 of 61 patients with ALS also had changes suggestive of stage II CTE in the brain. This is an intriguing association and could represent more than a coincidental link. Could trauma precipitate the pathologic changes in some patients with clinical ALS? Prospective studies to explore this possibility are ongoing.
Movement, Microglia, and the Stroke Epidemic
Functional Imaging in Movement Disorders
The role of imaging biomarkers to study neurodegenerative and movement disorders was the focus of the talk by David Eidelberg, MD, Investigator and Head of the Susan and Leonard Feinstein Center for Neurosciences at North Shore-LIJ Health System. His research focuses on the use of functional imaging and spatial covariance analysis to detect abnormal functional networks in neurologic diseases.
Using fludeoxyglucose PET, Dr. Eidelberg and his colleagues looked for specific patterns of glucose utilization associated with specific neurologic conditions. In a study of 167 patients, for example, they found that metabolic brain imaging could accurately discriminate patients with Parkinson disease, multiple system atrophy, and progressive supranuclear palsy 3 years before a definitive clinical diagnosis was made. The findings have been replicated by other investigators.
These results suggest that functional imaging and spatial covariance analysis can identify patients with specific parkinsonian syndromes early, leading to timely discussions about prognosis and treatment. These findings also have implications for optimizing clinical trial design, because functional imaging can ensure that trials enroll patients with the target disease, even in the early stages, and can be used to understand the factors that affect the placebo response.
Microglial Signatures in Health and Disease
Microglia are myeloid cells that are important for normal central nervous system (CNS) function. They are also involved in several disease states in which immune processes play a role, such as ALS, multiple sclerosis, and even Alzheimer disease. Differentiating microglia from peripheral monocytes or other CNS cells (oligodendrocytes, astrocytes, and neurons) is necessary to study how these cells contribute to pathologic processes.
Oleg Butovsky, PhD, from Brigham and Women’s Hospital and Harvard Medical School gave an excellent talk about his work using gene and microRNA array analyses and quantitative proteomic analyses to identify a genetic and molecular microglial signature that is dependent on transforming growth factor-beta signaling in rodents and humans. These findings are an important step in developing transgenic animal models that allow the study of the role of microglia in disease states.
Dr. Butovsky has developed mouse models to study microglia integrity and activity in ALS and experimental autoimmune encephalomyelitis. These models will lead to identification of therapeutic targets, and monoclonal antibodies that target microglia.
The Worldwide Stroke Epidemic
According to Jerome Chin, MD, PhD, MPH, lecturer in global health at the University of California, Berkeley, vascular disease is the major threat to the long-term survival of humans as a species, even more so than global warming and nuclear war. Almost one quarter of deaths worldwide are the result of ischemic heart disease and stroke, and the problem is getting worse because the stroke and heart attack rates are highest in low- and middle-income countries, where most of the world population resides.
Several factors are to blame: poor access to care; an aging world population; urbanization (more than one half of the world’s population now lives in cities) that leads to a sedentary lifestyle and access to processed foods; increasing obesity rates; and a high prevalence of smoking (in China, 45% of men smoke, and in Russia, 55% do). Moreover, between 25% and 50% of adults worldwide have hypertension, and most are untreated.
Dr. Chin reminded us that governments need policies and actions to stem the stroke epidemic. Public health measures that promote healthy diets and physical activity, and access to high-quality and affordable primary care, are a cornerstone of such policies. Many countries, however, do not have sufficient resources to address these issues alone.
The international medical community can help translate advances in prevention science into public action, collaborating with governments and civil societies. Dr. Chin described a successful example of an organization that engages international physicians and local communities: the Alliance for Stroke Awareness and Prevention Project in Uganda. Over the past few years, this organization has screened more than 50,000 people for hypertension and worked with the local health system to promote treatment. The organization is expanding into India and other countries.
Via Medscape – http://www.medscape.com/viewarticle/826277_2