Parkinson Disease: Georgia

Thurman DJ, Stevens JA, Rao JK, Anonymous00002. · National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA. · Neurology. · Pubmed #18250292 No free full text.

Abstract: OBJECTIVE: To develop a practice parameter for screening methods and assessments of risk for falls pertaining to patients likely to be seen in neurology practices. METHODS: Relevant literature was systematically reviewed and strength of evidence classified based on the American Academy of Neurology's criteria (Level A: established; Level B: probable; Level C: possible). RESULTS: An increased risk of falls is established among persons with diagnoses of stroke, dementia, and disorders of gait and balance (Level A) and probable among patients with Parkinson disease, peripheral neuropathy, lower extremity weakness or sensory loss, and substantial vision loss (Level B). A history of falling in the past year strongly predicts the likelihood of future falls (Level A). Screening measures have been developed to further assess risks of falls, including functional assessments that may be useful (Levels B and C). Several of these assess overlapping neurologic functions--i.e., gait, mobility, and balance--and there is insufficient evidence to assess whether they offer benefit beyond that provided by a standard neurologic examination. CONCLUSIONS: Patients with neurologic or general conditions associated with an increased risk of falling should be asked about recent falls and further examined for the presence of specific neurologic deficits that predict falls, which include gait and balance disorders; deficits of lower extremity strength, sensation, and coordination; and cognitive impairments. If substantial risks of falls are identified, appropriate interventions that are described in other evidence-based guidelines may be considered.

Parkinson AJ. · Arctic Investigations Program, National Center for Preparedness, Detection, and Control of Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK 99508, USA. · Emerg Infect Dis. · Pubmed #18258069 links to  free full text

Abstract: On 3 occasions over the past 125 years, scientists from around the world have worked together to organize scientific and exploration activities in polar regions (www.ipy.org). The first International Polar Year (IPY) in 1881-1884 marked the first major coordinated international scientific initiative to collect standardized meteorological and geophysical data in polar regions. Fifteen expeditions led by 12 nations amassed a large amount of data, but the scientific value was diminished by disjointed publication efforts and lack of long-term institutional commitment; lessons were learned and corrected in subsequent polar years. The second IPY began in 1932. Forty-four nations led expeditions in the Arctic and Antarctic, resulting in greater understanding of the aurora, magnetism, and meteorology. Air and marine navigation, radio operations, and weather forecasting were greatly improved as a result. The third IPY, in 1957-58, was renamed the International Geophysical Year and capitalized on technologic advances developed during World War II. Technologic and scientific momentum was redirected toward research, particularly to studies of the upper atmosphere, a legacy that continues to the present day. Notable achievements included launching the first satellite, measurement of atmospheric greenhouse gases, delineating the system of mid-ocean ridges, and confirming the theory of plate tectonics.

Hess JJ, Malilay JN, Parkinson AJ. · National Center for Environmental Health, CDC, Atlanta, Georgia 30341-3717, USA. · Am J Prev Med. · Pubmed #18929973 No free full text.

Abstract: Climate change-related risks are place-specific and path-dependent. Accordingly, location is an important determinant of hazardous exposure, and certain places will bear more risk than others. This article reviews the major environmental exposures associated with risky places in the U.S., including coastal regions, islands, the desert Southwest, vectorborne and zoonotic disease border regions, cities, and the U.S. Arctic (Alaska), with emphasis on exposures and vulnerable populations of concern. In addition to these hotspots, this study considers the ways in which the concept of place--the sense of human relationship with particular environments--will play a key role in motivating, developing, and deploying an effective public health response. In considering the importance of place, we highlight the concepts of community resilience and risk management, key aspects of a robust response to climate change in public health and other sectors.

Smith Y, Raju D, Nanda B, Pare JF, Galvan A, Wichmann T. · Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA. · Brain Res Bull. · Pubmed #18805468 links to  free full text

Abstract: Although we have gained significant knowledge in the anatomy and microcircuitry of the thalamostriatal system over the last decades, the exact function(s) of these complex networks remain(s) poorly understood. It is now clear that the thalamostriatal system is not a unique entity, but consists of multiple neural systems that originate from a wide variety of thalamic nuclei and terminate in functionally segregated striatal territories. The primary source of thalamostriatal projections is the caudal intralaminar nuclear group which, in primates, comprises the centromedian and parafascicular nuclei (CM/Pf). These two nuclei provide massive, functionally organized glutamatergic inputs to the whole striatal complex. There are several anatomical and physiological features that distinguish this system from other thalamostriatal projections. Although all glutamatergic thalamostriatal neurons express vGluT2 and release glutamate as neurotransmitter, CM/Pf neurons target preferentially the dendritic shafts of striatal projection neurons, whereas all other thalamic inputs are almost exclusively confined to the head of dendritic spines. This anatomic arrangement suggests that transmission of input from sources other than CM/Pf to the striatal neurons is likely regulated by dopaminergic afferents in the same manner as cortical inputs, while the CM/Pf axo-dendritic synapses do not display any particular relationships with dopaminergic terminals. A better understanding of the role of these systems in the functional circuitry of the basal ganglia relies on future research of the physiology and pathophysiology of these networks in normal and pathological basal ganglia conditions. Although much remains to be known about the role of these systems, recent electrophysiological studies from awake monkeys have provided convincing evidence that the CM/Pf-striatal system is the entrance for attention-related stimuli to the basal ganglia circuits. However, the processing and transmission of this information likely involves intrinsic GABAergic and cholinergic striatal networks, thereby setting the stage for complex physiological responses of striatal output neurons to CM/Pf activation. Finally, another exciting development that will surely generate significant interest towards the thalamostriatal systems in years to come is the possibility that CM/Pf may be a potential surgical target for movement disorders, most particularly Tourette syndrome and Parkinson's disease. Although the available clinical evidence is encouraging, these procedures remain empirical at this stage because of the limited understanding of the thalamostriatal systems.

Miller DB, O'Callaghan JP. · Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. · Metabolism. · Pubmed #18803966 No free full text.

Abstract: How early-life events "set the stage" for adult disease has emerged as a research focus. Historically, the epidemiology of disease risk factors has centered on adult life, with little scrutiny of early-life events. Here we review the concept that events in early life may contribute to late-life neurodegenerative disease development, with a focus on Parkinson disease (PD) and Alzheimer disease (AD). Suspect events in early life include infections, stress, poor nutrition, and environmental factors such as chemical and pesticide exposure. Adiposity appears to contribute to both PD and AD; and because early-life events contribute to the development of obesity, linkages may exist between early determinants of obesity and the subsequent development of these neurologic diseases. Many now suggest a life-course approach for determining the relative contributions of genetic and environmental factors in any chronic disease. This requires determining when during the life course that a given exposure has its greatest effect and how exposures may accumulate over the life span. The data for PD and AD suggest that a number of insults occurring early in life may lead or contribute to these diseases. More definitive knowledge of the key risk factors involved will be needed to implement intervention and preventative strategies early in life to dampen or prevent any adverse late-life outcomes.

Smith Y, Villalba R. · Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, Georgia, USA. · Mov Disord. · Pubmed #18781680 No free full text.

Abstract: Degeneration of the nigrostriatal dopaminergic system is the characteristic neuropathological feature of Parkinson's disease and therapy is primarily based on a dopamine replacement strategy. Dopamine has long been recognized to be a key neuromodulator of basal ganglia function, essential for normal motor activity. The recent years have witnessed significant advances in our knowledge of dopamine function in the basal ganglia. Although the striatum remains the main functional target of dopamine, it is now appreciated that there is dopaminergic innervation of the pallidum, subthalamic nucleus, and substantia nigra. A new dopaminergic- thalamic system has also been uncovered, setting the stage for a direct dopamine action on thalamocortical activity. The differential distribution of D1 and D2 receptors on neurons in the direct and indirect striato-pallidal pathways has been re-emphasized, and cholinergic interneurons are recognized as an intermediary mediator of dopamine-mediated communication between the two pathways. The importance and specificity of dopamine in regulating morphological changes in striatal projection neurons provides further evidence for the complex and multifarious mechanisms through which dopamine mediates its functional effects in the basal ganglia. In this review, the role of basal ganglia dopamine and its functional relevance in normal and pathological conditions will be discussed.

Sethi K. · Medical College of Georgia, Augusta, Georgia, USA. · Mov Disord. · Pubmed #18781679 No free full text.

Abstract: Levodopa has been the mainstay of symptomatic therapy for Parkinson Disease (PD) for 40 years providing benefit to virtually all patients. Levodopa therapy results in improved activities of daily living, enhanced quality of life, and improved mortality. However, the long-term use of levodopa is associated with the development of motor fluctuations and dyskinesia. In addition, levodopa therapy has further limitations. It has little or no effect on certain motor features (e.g. gait and balance dysfunction) and a non-motor symptom complex (autonomic dysfunction, pain syndromes, sleep disorders, mood disturbances, dementia). Further, multiple case reports illustrate the potential of levodopa and other dopaminergic agents to cause or reveal a series of impulse control disorders. This review highlights the levodopa unresponsive symptoms in PD.

Factor SA. · Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30329, USA. · Mov Disord. · Pubmed #18668624 No free full text.

Abstract: Freezing of gait (FOG), commonly seen in advanced Parkinson's disease (PD), has been classified as its fifth cardinal feature. However, its presence frequently leads to a misdiagnosis of PD. FOG is actually more common in atypical parkinsonism (AP): including vascular Parkinsonism (VP), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), and higher level gait disorders (HLGDs). VP is the result of multiple small vessel infarcts (lacunar state or Binswanger's disease), particularly involving the frontal, parietal, and basal ganglia regions. Approximately 50% have FOG (often referred to as lower body parkinsonism). FOG is also common in neurodegenerative forms of AP, present in 45-57%. Of these, FOG is present in 53% of PSP, 54% MSA, 54% DLB, 25% CBD, and 40% HLGD. It is generally seen in the late stages. There are two syndromes closely associated with AP that are dominated by FOG; pure akinesia (PA) and primary progressive freezing gait (PPFG). PA is characterized by akinesia of gait (including FOG), writing, and speech. Tremor, rigidity, dementia, and response to levodopa are notably absent. PPFG is defined by early FOG (often the initial feature) that progresses to include postural instability. It is accompanied by bradykinesia, rigidity, postural tremor, dementia, and levodopa unresponsiveness. Both syndromes are heterogeneous but PSP seems to be the most common cause. CBD and DLB can also present as PPFG. FOG is a common feature of AP and although typically occurring late in disease may also be an early symptom.

Mehta SH, Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, 1429 Harper Street, HF-1121, Augusta, GA 30912, USA. · Curr Neurol Neurosci Rep. · Pubmed #18590613 No free full text.

Abstract: Parkinson's disease is a progressive, widespread, neurodegenerative disease in which the involvement of the dopaminergic neurons of the substantia nigra results in significant dopamine depletion in the striatum. Newer imaging modalities reviewed here, using various radioligands, positron emission tomography, and single-photon emission computed tomography, have made it possible to assess the in vivo presynaptic and postsynaptic dopaminergic function. This is not only important from a diagnostic standpoint; these tests are being increasingly studied as surrogate markers to assess disease progression and responses to various interventions, including drugs. A brief comment on their role as a putative biomarker of the disease is also included. Because Parkinson's disease involves multiple neurotransmitter systems, neuroimaging of neurotransmitter systems other than dopamine is also discussed. Lastly, the evidence supporting the use of transcranial ultrasonography and substantia nigra hyperechogenicity in the diagnosis of Parkinson's disease is presented, along with some controversies that surround this technique.

Jones DC, Miller GW. · Neuroscience Division, Yerkes National Primate Research Center of Emory University, 954 Gatewood Rd NE, Atlanta, GA 30329, USA. · Biochem Pharmacol. · Pubmed #18555207 No free full text.

Abstract: Humans are routinely exposed to a vast array of environmental neurotoxicants, including pesticides, endocrine disrupters, and heavy metals. The long-term consequences of exposure have become a major human health concern as research has indicated strong associations between neurotoxicants and a variety of dopamine-related neurological disorders. Developmental exposure to pesticides including paraquat, organochlorines, and rotenone produce alterations in the dopaminergic system and has been linked to neurodegenerative disorders, including Parkinson's disease. Endocrine disrupters such as Bisphenol A, mimic estrogenic activity and impact various dopaminergic processes to enhance mesolimbic dopamine activity resulting in hyperactivity, attention deficits, and a heightened sensitivity to drugs of abuse. A second class of endocrine disrupters, the polychlorinated biphenyls, may act directly on dopaminergic processes to disrupt the dopamine system and produce Parkinson-like symptoms. Exposure to the heavy metal lead enhances dopaminergic activity and has been associated with attention deficits, Alzheimer's disease, and increased drug sensitivity. Manganese exposure, in contrast, results in dopamine deficiencies and Parkinson-like symptoms. Therefore, this commentary will discuss the effects and consequences that exposure to these three classes of environmental neurotoxicants have on the dopamine system and related behaviors and disorders. Finally, the recent hypothesis that exposure to environmental compounds which have effects on dopaminergic neurotransmission, including 2,4-dichlorophenoxyacetic acid, Bisphenol A, and multiple heavy metals, may potentiate drug-induced behaviors and increase the brain's vulnerability to drug addiction will be discussed.

Caudle WM, Colebrooke RE, Emson PC, Miller GW. · Center for Neurodegenerative Disease, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. · Trends Neurosci. · Pubmed #18471904 No free full text.

Abstract: Dopamine is a potentially toxic neurotransmitter that has long been speculated to contribute to the pathogenesis of Parkinson's disease (PD). Recent work has demonstrated the importance of proper storage of dopamine in vesicles to maintain dopamine homeostasis, thus protecting neurons from the detrimental effects of dopamine accumulation and breakdown in the cytosol. These studies suggest that factors which affect dopamine storage might increase the susceptibility of dopamine neurons to further environmental or genetic insults, exacerbating the neuronal degeneration that characterizes PD. This review seeks to revisit the pathogenicity of cytosolic dopamine and further address the critical role of neurotransmitter storage in dopamine-mediated neurotoxicity.

Galvan A, Wichmann T. · Department of Neurology, School of Medicine and Division of Sensorimotor Systems, Yerkes National Primate Center, Emory University, Atlanta, GA 30329, United States. · Clin Neurophysiol. · Pubmed #18467168 links to  free full text

Abstract: The motor signs of Parkinson's disease are thought to result in large part from a reduction of the level of dopamine in the basal ganglia. Over the last few years, many of the functional and anatomical consequences of dopamine loss in these structures have been identified, both in the basal ganglia and in related areas in thalamus and cortex. This knowledge has contributed significantly to our understanding of the link between the degeneration of dopamine neurons in the midbrain and the development of parkinsonism. This review discusses the evidence that implicates electrophysiologic changes (including altered discharge rates, increased incidence of burst firing, interneuronal synchrony, oscillatory activity, and altered sensorimotor processing) in basal ganglia, thalamus, and cortex, in parkinsonism. From these studies, parkinsonism emerges as a complex network disorder, in which abnormal activity in groups of neurons in the basal ganglia strongly affects the excitability, oscillatory activity, synchrony and sensory responses of areas of the cerebral cortex that are involved in the planning and execution of movement, as well as in executive, limbic or sensory functions. Detailed knowledge of these changes will help us to develop more effective and specific symptomatic treatments for patients with Parkinson's disease.

Hatcher JM, Pennell KD, Miller GW. · Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. · Trends Pharmacol Sci. · Pubmed #18453001 No free full text.

Abstract: Environmental factors have been shown to contribute to the incidence of Parkinson's disease (PD). Pesticides, which represent one of the primary classes of environmental agents associated with PD, share the common feature of being intentionally released into the environment to control or eliminate pests. Pesticides consist of multiple classes and subclasses of insecticides, herbicides, rodenticides, fungicides, fumigants and others and exhibit a vast array of chemically diverse structures. In this review we examine the evidence regarding the ability of each of the major pesticide subclasses to increase the incidence of PD. We propose that, from a toxicological perspective, it would be beneficial to identify specific subclasses, common structural features and the propensity for widespread human exposure when considering the potential role in PD, rather than using the overly broad term of 'pesticides' to describe this diverse group of chemicals. Furthermore, these chemicals and their environmentally relevant combinations should be evaluated for their ability to promote or accelerate PD and not merely for being singular causative agents.

Papa SM. · Department of Neurology, Emory University School of Medicine, 6000 WMRC, 101 Woodruff Circle, Atlanta, Georgia, 30322, USA. · Exp Neurol. · Pubmed #18433745 No free full text.

This publication has no abstract.

Gross RE. · Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30022, USA. · Neurotherapeutics. · Pubmed #18394570 No free full text.

Abstract: Fifteen years after its resurrection, pallidotomy for Parkinson's disease (PD) and dystonia has once again been supplanted, this time by deep brain stimulation (DBS). Did this occur because pallidotomy was not effective or safe, or because DBS was found to be more effective and safer? This review focuses on the evidence-and its quality-supporting the effectiveness and safety of pallidotomy for PD and dystonia, and the comparative effectiveness and safety of DBS of the subthalamic nucleus (STN) and globus pallidus pars interna (GPi). Discussed first are the determinants of "level 1" recommendations, including the confounding effects on interpretation of randomized clinical trials (RCTs) that fail to control for patient bias (i.e., placebo effects). Although several RCTs have been performed comparing unilateral pallidotomy to medical therapy, GPi DBS, or STN DBS for PD, none controlled for patient bias. Comparison of these trials to estimate the placebo effect, and examination of retrospective case series, suggests that the true effectiveness of unilateral pallidotomy is 20% to 30% reduction of 'off' total motor UPDRS scores, which is similar to the effects of unilateral GPi DBS or STN DBS, but less than bilateral STN DBS. At experienced centers, safety of unilateral pallidotomy appears equivalent to unilateral DBS, but bilateral DBS is likely safer than bilateral pallidotomy. Whereas there have been no RCTs of pallidotomy for dystonia, two double-blind, sham-controlled RCTs of bilateral GPi DBS were performed. Nevertheless, limited uncontrolled series suggest that bilateral pallidotomy is similar to GPi DBS in effectiveness and safety for dystonia. Thus, pallidotomy was not rejected because of lack of effectiveness or safety, and it remains a viable alternative in situations where DBS is not available or not feasible.

Factor SA. · Department of Neurology, Emory University School of Medicine, 1841 Clifton Road NE, Atlanta, Georgia 30329, USA. · Neurotherapeutics. · Pubmed #18394561 No free full text.

Abstract: Symptomatic medical therapies for Parkinson's disease (PD) have been disease modifying and have led to improvement in daily function, quality of life, and survival. For 40 years, these therapies have been primarily dopaminergic, and currently include the dopamine (DA) precursor levodopa (LD), DA agonists, catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors. The roles of all these classes of agents have evolved, with significant changes occurring since the early 2000s. This article reviews the current literature for each of these classes of drugs, with a focus on efficacy and place in the therapeutic scheme. Levodopa is no longer considered to be toxic and, thus, its early use is not only appropriate but recommended. Ergot agonists are no longer in use, and new agents administered in patch form or subcutaneous injections have been approved. The COMT inhibitor tolcapone, with its significant efficacy, has been reintroduced, and two new MAO inhibitors have been approved. Selected safety issues are discussed, including the incidence of melanoma in relation to LD; pathological gambling and DA agonists; hepatic toxicity of tolcapone; and the tyramine or so-called cheese reaction with MAO B inhibitors. The article closes with a discussion of future directions and new drugs under development.

Mehta SH, Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. · CNS Spectr. · Pubmed #18323761 links to  free full text

Abstract: Sleep dysfunction is common among patients with Parkinson's disease and occurs in approximately two thirds of patients. The problems range from nocturnal issues such as difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime problems such as excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in Parkinson's disease. Dopamine plays an important role in maintaining wakefulness. To improve sleep in Parkinson's disease, it is important to achieve the critical balance of adequate dopaminergic therapy and control of symptoms. Increased dopaminergic agents can cause dyskinesias and painful dystonia, and undertreatment can cause nighttime akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs commonly used in Parkinson's disease can also affect sleep. In patients with advanced Parkinson's disease, deep brain stimulation of the subthalamic nucleus has a favorable impact on sleep quality and sleep architecture.

Parkinson AJ. · Arctic Investigations Program, Centers for Disease Control & Prevention, USA. · Alaska Med. · Pubmed #18323371 No free full text.

Abstract: Life expectancy in Arctic populations has greatly improved over the last 50 years. Much of this improvement can be attributed to health research that has resulted in a reduction in morbidity and mortality from infectious diseases, such as tuberculosis, and the vaccine-preventable diseases of childhood. However, despite these improvements in health indicators of Arctic residents, life expectancy and infant mortality remain higher in indigenous Arctic residents in the US Arctic, northern Canada, and Greenland when compared to Arctic residents of Nordic countries. The International Polar Year (IPY) represents a unique opportunity to focus world attention on Arctic human health and to further stimulate Circumpolar cooperation on emerging Arctic human health concerns. The Arctic Human Health Initiative (AHHI) is an Arctic Council IPY initiative that aims to build and expand on existing Arctic Council and International Union for Circumpolar Health (IUCH) human health research activities. The human health legacy of the IPY will be increased visibility of the human health concerns of Arctic communities, revitalization of cooperative Arctic human health research focused on those concerns, the development of health policies based on research findings, and the subsequent implementation of appropriate interventions, prevention and control measures at the community level.

Esper CD, Weiner WJ, Factor SA. · Department of Neurology Emory University School of Medicine, Atlanta, GA, USA. · Rev Neurol Dis. · Pubmed #18195676 No free full text.

Abstract: Since progressive supranuclear palsy (PSP) was first reported as a separate clinicopathological entity in 1964, hundreds of other cases have been recorded, and PSP is now one of the most common atypical Parkinson-plus disorders. Diagnostic criteria have been developed by the National Institute of Neurological Disorders and Stroke and the Society for PSP, Inc. Because there is no biological marker for PSP, definitive diagnosis depends on neuropathological examination. Characteristics of PSP include gait disturbances, supranuclear ophthalmoplegia, axial limb rigidity, and frontal lobe dysfunction. Although there are no treatments that alter the natural history of disease in PSP and no drugs that provide significant symptomatic benefits, several supportive measures are available.

Hess DC, Borlongan CV. · Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. · Cell Prolif. · Pubmed #18181951 No free full text.

Abstract: Cells of the central nervous system were once thought to be incapable of regeneration. This dogma has been challenged in the last decade with studies showing new, migrating stem cells in the brain in many rodent injury models and findings of new neurones in the human hippocampus in adults. Moreover, there are reports of bone marrow-derived cells developing neuronal and vascular phenotypes and aiding in repair of injured brain. These findings have fuelled excitement and interest in regenerative medicine for neurological diseases, arguably the most difficult diseases to treat. There are numerous proposed regenerative approaches to neurological diseases. These include cell therapy approaches in which cells are delivered intracerebrally or are infused by an intravenous or intra-arterial route; stem cell mobilization approaches in which endogenous stem and progenitor cells are mobilized by cytokines such as granulocyte colony stimulatory factor (GCSF) or chemokines such as SDF-1; trophic and growth factor support, such as delivering brain-derived neurotrophic factor (BDNF) or glial-derived neurotrophic factor (GDNF) into the brain to support injured neurones; these approaches may be used together to maximize recovery. While initially, it was thought that cell therapy might work by a 'cell replacement' mechanism, a large body of evidence is emerging that cell therapy works by providing trophic or 'chaperone' support to the injured tissue and brain. Angiogenesis and neurogenesis are coupled in the brain. Increasing angiogenesis with adult stem cell approaches in rodent models of stroke leads to preservation of neurones and improved functional outcome. A number of stem and progenitor cell types has been proposed as therapy for neurological disease ranging from neural stem cells to bone marrow derived stem cells to embryonic stem cells. Any cell therapy approach to neurological disease will have to be scalable and easily commercialized if it will have the necessary impact on public health. Currently, bone marrow-derived cell populations such as the marrow stromal cell, multipotential progenitor cells, umbilical cord stem cells and neural stem cells meet these criteria the best. Of great clinical significance, initial evidence suggests these cell types may be delivered by an allogeneic approach, so strict tissue matching may not be necessary. The most immediate impact on patients will be achieved by making use of the trophic support capability of cell therapy and not by a cell replacement mechanism.

Kessler A, Rezak M. · Department of Neurology, Emory Univeristy School of Medicine, Atlanta, Georgia, USA. · Dis Mon. · Pubmed #17586329 No free full text.

This publication has no abstract.

Rommelfanger KS, Weinshenker D. · Department of Human Genetics, Emory University, Atlanta, GA 30322, United States. · Biochem Pharmacol. · Pubmed #17416354 No free full text.

Abstract: Parkinson's disease (PD) affects approximately 1% of the world's aging population. Despite its prevalence and rigorous research in both humans and animal models, the etiology remains unknown. PD is most often characterized by the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), and models of PD generally attempt to mimic this deficit. However, PD is a true multisystem disorder marked by a profound but less appreciated loss of cells in the locus coeruleus (LC), which contains the major group of noradrenergic neurons in the brain. Historic and more recent experiments exploring the role of norepinephrine (NE) in PD will be analyzed in this review. First, we examine the evidence that NE is neuroprotective and that LC degeneration sensitizes DA neurons to damage. The second part of this review focuses on the potential contribution of NE loss to the behavioral symptoms associated with PD. We propose that LC loss represents a crucial turning point in PD progression and that pharmacotherapies aimed at restoring NE have important therapeutic potential.

DeLong MR, Wichmann T. · Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA. · Arch Neurol. · Pubmed #17210805 links to  free full text

Abstract: Views of the anatomy and function of the basal ganglia and their role in motor and nonmotor disorders have undergone major revisions during the past decades. The basal ganglia are now appreciated as components of parallel, reentrant cortico-subcortical circuits, which originate from individual cortical areas, traverse the basal ganglia and thalamus, and terminate in their respective areas of origin in the frontal lobe. Further research and clinical experience have resulted in new insights and perspectives on the details of the circuitry and on the role of these structures in Parkinson disease and other basal ganglia disorders. On the basis of anatomical and physiological studies and the striking success of focused surgical interventions, it seems appropriate to view these varied clinical disorders as circuit disorders, resulting from pathologic disturbances in neuronal activity throughout specific cortico-subcortical loops.

Wichmann T, DeLong MR. · Department of Neurology, Emory University, Atlanta, GA 30322, USA. · J Neural Transm Suppl. · Pubmed #17017504 No free full text.

Abstract: In the traditional model of the pathophysiology of parkinsonism, parkinsonian motor signs are viewed as the result of changes in discharge rates in the basal ganglia. However, not all experimental findings can be explained by rate changes alone, and changes in discharge patterns in these nuclei are increasingly emphasized as pathophysiologically important, including changes in burst discharges, in synchrony, and in oscillatory activity. This brief review highlights the pathophysiologic relevance of these rate and pattern changes in the pathophysiology of parkinsonism.

Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia,1429 Harper Street, HF-1121 Augusta, GA 30912, USA. · Expert Rev Neurother. · Pubmed #17009915 No free full text.

Abstract: Dopaminergic therapies, including levodopa and dopamine agonists, are the mainstays of therapy in Parkinson's disease. With the exception of the injectable short-acting dopamine agonist apomorphine, there is no other widely available non-oral dopaminergic therapy. Rotigotine is a lipid-soluble, non-ergot, D3, D2, D1 dopamine receptor agonist that has demonstrated efficacy as an alternative therapeutic option in both early and advanced Parkinson's disease. More importantly, it is uniquely formulated as a transdermal patch delivery system allowing for continuous, once-daily administration and better patient compliance. Preclinical and clinical trials have shown rotigotine to be a well-tolerated and effective treatment for early-stage Parkinson's disease. Rotigotine has also shown promise as adjunctive therapy with levodopa for the treatment of advanced Parkinson's disease.