Parkinson Disease: Texas

Maricich SM, Zoghbi HY. · Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA. · Cell. · Pubmed #16839867 No free full text.

Abstract: Advances in understanding basic developmental and physiological processes often have direct relevance to human disease. They provide insights into pathogenic mechanisms and reveal new pathways that can be exploited in diagnosis and the development of therapeutics.

Narayana S, Jacks A, Robin DA, Poizner H, Zhang W, Franklin C, Liotti M, Vogel D, Fox PT. · Research Imaging Center, Honors College, The University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive MSC 6240, San Antonio, TX 78229-3900, USA. · Am J Speech Lang Pathol. · Pubmed #19029533 No free full text.

Abstract: PURPOSE: To explore the use of noninvasive functional imaging and "virtual" lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson's disease. Here, we report the use of positron emission tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson's disease. METHOD: Perceptual and acoustic speech measures, as well as cerebral blood flow during speech as measured by PET, were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with speech produced with DBS on. RESULTS: Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. "Virtual" lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. CONCLUSIONS: This case report provides evidence that impaired speech production accompanying STN-DBS may result from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities.

Weidong Le, Shen Chen, Jankovic J. · Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Neuroscientist. · Pubmed #19008336 No free full text.

Abstract: Parkinson disease (PD) probably represents a syndrome of different disorders and origins converging into a relatively uniform neurodegenerative process. Although clinical-pathological studies have suggested that the presymptomatic phase of PD may be relatively short, perhaps less than a decade, the authors postulate that the pathogenic mechanisms may begin much earlier, possibly even in the prenatal period. Thus, some patients with PD may be born with a fewer than normal number of dopaminergic (and nondopaminergic) neurons as a result of genetic or other abnormalities sustained during the prenatal or perinatal period; as a result of normal age-related neuronal attrition, they eventually reach the critical threshold (60% or more) of neuronal loss needed for onset of PD to become clinically manifest. The authors review the emerging evidence that genetic disruption of normal development, coupled with subsequent environmental factors (the so called multiple-hit hypothesis), plays an important role in the etiopathogenesis of PD.

Hermanns M. · American Parkinon's Disease Association, East Texas Chapter, USA. · RN. · Pubmed #18942321 No free full text.

This publication has no abstract.

Chitnis S. · Clinical Center for Movement Disorders, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · Neurol Clin. · Pubmed #18774441 No free full text.

Abstract: Parkinsonism is a syndrome characterized by a combination of cardinal features including resting tremor, bradykinesia, rigidity, and loss of postural reflexes. The most common presentation of parkinsonism is the idiopathic variety first described by James Parkinson in 1817 now known as Parkinson's disease (PD). This article focuses on identifying the different subtypes of PD, with the recognition that treatment approaches may differ depending on the initial presenting feature. It also addresses issues related to the recognition and treatment of nonmotor comorbidities of PD, such as autonomic dysfunction and neuropsychiatric problems including depression and dementia.

Dewey RB. · University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · Neurol Clin. · Pubmed #18774440 No free full text.

Abstract: Given the magnitude of the problem of motor fluctuations in patients who have Parkinson's disease treated with levodopa, a significant effort has been expended by physicians, researchers, and pharmaceutical manufacturers over the years to find effective treatments. This article briefly reviews the medical options for managing motor fluctuations that are in common use in the United States or that are expected to be available soon.

Ferrara JM, Stacy M. · Baylor College of Medicine, Houston, TX, USA. · CNS Spectr. · Pubmed #18704024 links to  free full text

Abstract: Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

Ciucci MR, Ma ST, Kane JR, Ahrens AM, Schallert T. · Department of Psychology, University of Texas, 1 University Station A8000, Austin, TX 78712, USA. · Parkinsonism Relat Disord. · Pubmed #18585950 No free full text.

Abstract: Recent evidence in animal models of Parkinson's disease (PD) suggests that exercise and other forms of motor enhancement can be beneficial when applied during the degeneration of dopamine neurons. Behaviours that depend on adequate levels of striatal dopamine may provide particularly favourable targets for therapeutic motor interventions. Task-specific motor enrichment procedures have been used to improve functional and neural outcomes following unilateral infusions of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway in rats. In contrast, forced non-use procedures can exaggerate the degree of degeneration. Limb-use akinesia and ultrasonic vocalization in the 50-kHz range may be useful behavioural indices of nigrostriatal integrity and may model common deficits found in PD. These deficits in movement initiation and fine sensorimotor control are potential targets for early training interventions.

Encarnacion EV, Hauser RA. · Department of Neurology, Texas A&M Health Sciences Center, Scott and White National Parkinson Foundation Plummer Movement Disorders Center, Temple, TX, USA. · Eur Neurol. · Pubmed #18480609 links to  free full text

Abstract: Levodopa is the most effective agent to alleviate motor dysfunction in Parkinson's disease but its long-term use is associated with the development of dyskinesias. Although the pathogenic processes behind the development of levodopa-induced dyskinesias are still being elucidated, it appears that chronic administration of this short-lived agent results in nonphysiologic pulsatile stimulation of striatal neurons and abnormal firing patterns in the basal ganglia. Dyskinesias have been associated with decreased quality of life, and a number of methodologies to evaluate severity of dyskinesias are now available. Strategies to avoid, reduce, or eliminate dyskinesias include providing more continuous dopaminergic stimulation, administering an antidyskinetic agent, and surgery. Several new compounds that may provide an antidyskinetic effect are also under investigation.

Orr JD. · Neurology Associates of Arlington, 2800 E. Broad Street, Mansfield, TX 76063, USA. · Curr Atheroscler Rep. · Pubmed #18366980 No free full text.

Abstract: Overwhelming evidence now shows that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) are safe and effective in primary and secondary prevention of cardiovascular disease. Atherosclerosis, the primary cause of heart disease, is directly and independently related to hypercholesterolemia and inflammation, and statins have multiple and independent effects on these conditions. New evidence for the use of statins in neurologic disease is mounting, and the range of therapeutic applications is formidable. Statins are beginning to show benefits in a wide range of neurologic conditions, from common ischemic stroke to rare congenital neurometabolic storage diseases, from acute brain injury to chronic central nervous system inflammation, and from prevention of neurodegenerative disease to acute neuroprotection. A diverse therapeutic spectrum is explained by shared pathogenetic mechanisms of neurologic disease and the manifold pharmacodynamic effects of statins.

Jankovic J. · Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, Texas 77030-3498, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #18344392 No free full text.

Abstract: OBJECTIVE: Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. METHODS: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included "Parkinson's disease", "diagnosis" and "signs and symptoms". RESULTS: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. CONCLUSIONS: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

Stamey W, Jankovic J. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. · Neurologist. · Pubmed #18332838 No free full text.

Abstract: OBJECTIVES: The primary aim of this article is to critically review the clinical features and comorbidities, epidemiology, pathophysiology, and treatment of impulse control disorder (ICD) associated with Parkinson disease (PD). METHODS: References for this review were identified by searches of PubMed from 1980 until January 2008 with the terms "Parkinson disease," "impulse control," "pathologic gambling,""hypersexuality," "levodopa," and "dopamine agonists." Articles were also identified through searches of the authors' own files. Only papers published in English were reviewed. RESULTS: Pathologic gambling has emerged as one of the most prominent ICDs, although hypersexuality, compulsive shopping and other manifestations of obsessive-compulsive disorder may also dominate PD-related behavioral manifestations. Affected patients may demonstrate a pattern of self-escalation of dopaminergic medication dosing which may lead to a state of dependency. CONCLUSIONS: Patients most commonly affected by ICD, such as pathologic gambling and hypersexuality, are males who develop PD at a younger age, and those with a previous history of mood disorder, alcohol abuse, or obsessive-compulsive disorder. Dopaminergic drugs, particularly dopamine agonists, play an important role in triggering these nonmotor symptoms.

Pan T, Kondo S, Le W, Jankovic J. · Parkinson's Disease Research Laboratory, Baylor College of Medicine, Houston, TX 77030, USA. · Brain. · Pubmed #18187492 links to  free full text

Abstract: The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of alpha-synuclein and the increase of intracellular concentrations of non-mutant alpha-synuclein have been associated with Parkinson's disease phenotype. The demonstration that alpha-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant alpha-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.

Jankovic J. · Parkinson's Disease and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA. · Lancet Neurol. · Pubmed #18093549 No free full text.

This publication has no abstract.

Tansey MG, Frank-Cannon TC, McCoy MK, Lee JK, Martinez TN, McAlpine FE, Ruhn KA, Tran TA. · Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA. · Front Biosci. · Pubmed #17981581 No free full text.

Abstract: The inflammatory response in the brain associated with most chronic neurodegenerative diseases is termed neuroinflammation. Neuropathological and neuroradiological studies indicate that in certain neurodegenerative disorders neuroinflammation may be detectable years before significant loss of neurons occurs. In this review, we discuss the evidence from human studies and experimental models that implicate neuroinflammatory processes in the progressive neurodegeneration of the nigrostriatal pathway, the hallmark of Parkinson's Disease (PD). We discuss the neurotoxic role of microglia-derived inflammatory mediators which are suspected to hasten the death of nigral dopaminergic neurons, in particular the pro-inflammatory cytokine Tumor Necrosis Factor (TNF) and its downstream signaling pathways. We also entertain the possibility that chronic microglia activation links proteinopathies to neurodegeneration. The rationale for current and future use of anti-inflammatory approaches to protect vulnerable neuronal populations in PD is also reviewed.

Goel A, Kunnumakkara AB, Aggarwal BB. · Gastrointestinal Cancer Research Laboratory, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX, United States. · Biochem Pharmacol. · Pubmed #17900536 No free full text.

Abstract: Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

Tansey MG, McCoy MK, Frank-Cannon TC. · Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. · Exp Neurol. · Pubmed #17720159 No free full text.

Abstract: Most acute and chronic neurodegenerative conditions are accompanied by neuroinflammation; yet the exact nature of the inflammatory processes and whether they modify disease progression is not well understood. In this review, we discuss the key epidemiological, clinical, and experimental evidence implicating inflammatory processes in the progressive degeneration of the dopaminergic (DA) nigrostriatal pathway and their potential contribution to the pathophysiology of Parkinson's disease (PD). Given that interplay between genetics and environment are likely to contribute to risk for development of idiopathic PD, recent data showing interactions between products of genes linked to heritable PD that function to protect DA neurons against oxidative or proteolytic stress and inflammation pathways will be discussed. Cellular mechanisms activated or enhanced by inflammatory processes that may contribute to mitochondrial dysfunction, oxidative stress, or apoptosis of dopaminergic (DA) neurons will be reviewed, with special emphasis on tumor necrosis factor (TNF) and interleukin-1-beta (IL-1beta) signaling pathways. Epigenetic factors which have the potential to trigger neuroinflammation, including environmental exposures and age-associated chronic inflammatory conditions, will be discussed as possible 'second-hit' triggers that may affect disease onset or progression of idiopathic PD. If inflammatory processes have an active role in nigrostriatal pathway degeneration, then evidence should exist to indicate that such processes begin in the early stages of disease and that they contribute to neuronal dysfunction and/or hasten neurodegeneration of the nigrostriatal pathway. Therapeutically, if anti-inflammatory interventions can be shown to rescue nigral DA neurons from degeneration and lower PD risk, then timely use of anti-inflammatory therapies should be investigated further in well-designed clinical trials for their ability to prevent or delay the progressive loss of nigral DA neurons in genetically susceptible populations.

Santamaria AB, Cushing CA, Antonini JM, Finley BL, Mowat FS. · ENVIRON International Corporation, Houston, Texas 77042, USA. · J Toxicol Environ Health B Crit Rev. · Pubmed #17710609 No free full text.

Abstract: Recent studies report that exposure to manganese (Mn), an essential component of welding electrodes and some steels, results in neurotoxicity and/or Parkinson's disease (PD) in welders. This "state-of-the-science" review presents a critical analysis of the published studies that were conducted on a variety of Mn-exposed occupational cohorts during the last 100 yr, as well as the regulatory history of Mn and welding fumes. Welders often perform a variety of different tasks with varying degrees of duration and ventilation, and hence, to accurately assess Mn exposures that occurred in occupational settings, some specific information on the historical work patterns of welders is desirable. This review includes a discussion of the types of exposures that occur during the welding process--for which limited information relating airborne Mn levels with specific welding activities exists--and the human health studies evaluating neurological effects in welders and other Mn-exposed cohorts, including miners, millers, and battery workers. Findings and implications of studies specifically conducted to evaluate neurobehavioral effects and the prevalence of PD in welders are also discussed. Existing exposure data indicate that, in general, Mn exposures in welders are less than those associated with the reports of clinical neurotoxicity (e.g., "manganism") in miners and smelter workers. It was also found that although manganism was observed in highly exposed workers, the scant exposure-response data available for welders do not support a conclusion that welding is associated with clinical neurotoxicity. The available data might support the development of reasonable "worst-case" exposure estimates for most welding activities, and suggest that exposure simulation studies would significantly refine such estimates. Our review ends with a discussion of the data gaps and areas for future research.

Jankovic J, Stacy M. · Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas 77030, USA. · CNS Drugs. · Pubmed #17630819 No free full text.

Abstract: Parkinson's disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition; however, with continued treatment and as the disease progresses, up to 80% of patients experience 'wearing-off' symptoms, dyskinesias and other motor complications. These levodopa-associated problems may become disabling and profoundly affect quality of life. Medications commonly used to manage these symptoms include monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, the NMDA receptor antagonist amantadine and dopamine receptor agonists.Agents that block MAO-B, such as rasagiline and selegiline, are used as both initial and adjunctive therapy in patients with Parkinson's disease. These medications increase concentrations of dopamine in the brain by blocking its reuptake from the synaptic cleft, a mechanism that can slow motor decline, increase 'on' time and improve symptoms of Parkinson's disease. Adverse events with these agents can include confusion, hallucination and orthostatic hypotension. MAO-B inhibition may elicit drug-drug interactions if administered with TCAs, SSRIs or SNRIs. Conventional oral selegiline is associated with potentially harmful plasma concentrations of three major amphetamine metabolites, although metabolite concentrations are significantly lower with a new orally disintegrating tablet (ODT) selegiline formulation. Selegiline ODT is also absorbed more efficiently and shows less pharmacokinetic variability than conventional oral selegiline.COMT mediates peripheral catabolism of levodopa. Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Given adjunctively with levodopa, COMT inhibitors can decrease 'off' time and increase 'on' time, as well as lower the daily levodopa dose. Although more potent than entacapone, tolcapone requires monitoring for hepatotoxicity.Amantadine is a noncompetitive NMDA receptor antagonist shown to lower dyskinesia scores and improve motor complications in patients with Parkinson's disease when given adjunctively with levodopa.Dopamine agonists, also used as initial and adjunctive therapy in Parkinson's disease, improve motor response and decrease 'off' time purportedly through direct stimulation of dopamine receptors. Current dopamine agonists include bromocriptine, pergolide, cabergoline, lisuride, apomorphine, pramipexole, ropinirole and rotigotine. Although effective, this class of medications can be associated with cardiovascular and psychiatric adverse effects that can limit their utility.All medications used to manage levodopa-associated motor complications in patients with Parkinson's disease have had differing degrees of success. Although head-to-head comparisons of drugs within classes are rare, some differences have emerged related to effects on motor fluctuations, dyskinesias and on/off times, as well as to adverse effects. When choosing a drug to treat levodopa-induced complications, it is important to consider the risks and benefits of the different classes and of the specific agents within each class, given the different efficacy and safety profiles of each.

Kenney C, Jankovic J. · Parkinson's disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, Texas 77030, USA. · Expert Opin Pharmacother. · Pubmed #17563266 No free full text.

Abstract: Dopamine agonists are effective in delaying levodopa-induced dyskinesia in early Parkinson's disease (PD) and reducing motor fluctuations in advanced PD. Rotigotine, a novel dopamine receptor agonist, improves motor function in both early and advanced PD using a transdermal route of administration. A smaller, but convincing body of data, supports its ability to ameliorate the symptoms of restless legs syndrome as well. The side-effect profile mimics other dopamine agonists, with the addition of application-site reactions, most of which are mild-to-moderate. Advantages over existing dopamine agonists include once-daily administration, absence of food interactions, maintenance of stable plasma levels and utility in patients with swallowing difficulties.

Sheffield JK, Jankovic J. · Department of Neurology, Baylor College of Medicine, Parkinson's Disease Center & Movement Disorders Clinic, 6550 Fannin, Suite 1801, Houston, TX 77030, USA. · Expert Rev Neurother. · Pubmed #17563247 No free full text.

Abstract: Botulinum toxins are an effective treatment modality for a growing number of neurologic conditions. Although there has been varied interest and success in their use, they have been studied for a variety of conditions associated with Parkinson's disease. Conditions reviewed in this paper include hand and jaw tremor, dystonia, blepharospasm and apraxia of eyelid opening, bruxism, camptocormia, freezing of gait, sialorrhea and constipation. We will make comments when applicable on our unique experience with botulinum toxin in these conditions. Other conditions associated with Parkinson's disease, which will not be reviewed here, but may benefit from botulinum toxin treatment include anterocollis (also known as dropped head syndrome), hyperhidrosis, seborrhea and overactive bladder.

Deng H, Le W, Jankovic J. · Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. · Brain. · Pubmed #17353225 links to  free full text

Abstract: Essential tremor (ET), the cause of which remains poorly understood, is one of the most common neurological disorders. While environmental agents have been proposed to play a role, genetic factors are believed to contribute to its onset. Thus far, three gene loci (ETM1 on 3q13, ETM2 on 2p24.1 and a locus on 6p23) have been identified in patients and families with the disorder. In addition, a Ser9Gly variant in the dopamine D3 receptor gene on 3q13 has been suggested to be a risk factor. Moreover, genetically deficient animal models express a phenotype that overlaps with some clinical characteristics of the human form of the illness. Further analyses of these genetic abnormalities may lead to the identification of causative mutations and a better understanding of the molecular mechanisms in this common movement disorder.

Rao SS, Hofmann LA, Shakil A. · University of Texas Southwestern Medical School at Dallas Family Medicine Residency Program, Dallas, Texas 75390, USA. · Am Fam Physician. · Pubmed #17186710 links to  free full text

Abstract: Parkinson's disease is a common neurodegenerative disorder that can cause significant disability and decreased quality of life. The cardinal physical signs of the disease are distal resting tremor, rigidity, bradykinesia, and asymmetric onset. Levodopa is the primary treatment for Parkinson's disease; however, its long-term use is limited by motor complications and drug-induced dyskinesia. Dopamine agonists are options for initial treatment and have been shown to delay the onset of motor complications. However, dopamine agonists are inferior to levodopa in controlling motor symptoms. After levodopa-related motor complications develop in advanced Parkinson's disease, it is beneficial to initiate adjuvant therapy with dopamine agonists, catechol O-methyltransferase inhibitors, or monoamine oxidase-B inhibitors. Deep brain stimulation of the subthalamic nucleus has been shown to ameliorate symptoms in patients with advanced disease. Depression, dementia, and psychosis are common psychiatric problems associated with Parkinson's disease. Psychosis is usually drug induced and can be managed initially by reducing antiparkinsonian medications. The judicious use of psychoactive agents may be necessary. Consultation with a subspecialist is often required.

Kishida KT, Klann E. · Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA. · Antioxid Redox Signal. · Pubmed #17115936 No free full text.

Abstract: Increasing evidence suggests that reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, act as necessary signaling molecules in processes underlying cognition. Moreover, ROS have been shown to be necessary in molecular process underlying signal transduction, synaptic plasticity, and memory formation. Research from several laboratories suggests that NADPH oxidase is an important source of superoxide in the brain. Evidence is presented here to show that ROS are in fact important signaling molecules involved in synaptic plasticity and memory formation. Moreover, evidence that the NADPH oxidase complex is a key regulator of ROS generation in synaptic plasticity and memory formation is discussed. Understanding redox signaling in the brain, including the sources and molecular targets of ROS, are important for a full understanding of the signaling pathways that underlie synaptic plasticity and memory. Knowledge of ROS function in the brain also is critical for understanding aging and neurodegenerative diseases of the brain given that several of these disorders, including Alzheimer's disease and Parkinson disease, may be exacerbated by the unregulated generation of ROS.

Sohrabji F, Lewis DK. · Department of Neuroscience and Experimental Therapeutics, TAMU Health Science Center, College Station, TX 77843-1114, USA. · Front Neuroendocrinol. · Pubmed #17069877 links to  free full text

Abstract: Since its' discovery over 20 years ago, BDNF has been shown to play a key role in neuronal survival, in promoting neuronal regeneration following injury, regulating transmitter systems and attenuating neural-immune responses. Estrogen's actions in the young and mature brain, and its role in neurodegenerative diseases in many cases overlaps with those observed for BDNF. Reduced estrogen and BDNF are observed in patients with Parkinson's disease and Alzheimer's disease, while high estrogen levels are a risk factor for development of multiple sclerosis. Estrogen receptors, which transduce the actions of estrogen, colocalize to cells that express BDNF and its receptor trkB, and estrogen further regulates the expression of this neurotrophin system. This review describes the distribution of BDNF and trkB expressing cells in the forebrain, and the roles of estrogen and the BDNF-trkB neurotrophin system in Parkinson's disease, Alzheimer's disease and multiple sclerosis.