Parkinson Disease: US Mid-Atlantic

Price A, Filoteo JV, Maddox WT. · Department of Psychology, Elizabethtown College, Elizabethtown, PA 17022, United States. · Neuropsychologia. · Pubmed #19428385 links to  free full text

Abstract: Measures of explicit rule-based category learning are commonly used in neuropsychological evaluation of individuals with Parkinson's disease (PD) and the pattern of PD performance on these measures tends to be highly varied. We review the neuropsychological literature to clarify the manner in which PD affects the component processes of rule-based category learning and work to identify and resolve discrepancies within this literature. In particular, we address the manner in which PD and its common treatments affect the processes of rule generation, maintenance, shifting and selection. We then integrate the neuropsychological research with relevant neuroimaging and computational modeling evidence to clarify the neurobiological impact of PD on each process. Current evidence indicates that neurochemical changes associated with PD primarily disrupt rule shifting, and may disturb feedback-mediated learning processes that guide rule selection. Although surgical and pharmacological therapies remediate this deficit, it appears that the same treatments may contribute to impaired rule generation, maintenance and selection processes. These data emphasize the importance of distinguishing between the impact of PD and its common treatments when considering the neuropsychological profile of the disease.

Dadabhai A, Friedenberg FK. · Temple University Hospital, Temple University School of Medicine, Gastroenterology Section, Parkinson Pavilion, 8th Floor, 3401 North Broad Street, PA 19140, Philadelphia, USA. · Expert Opin Drug Saf. · Pubmed #19236223 No free full text.

Abstract: Rabeprazole is a proton pump inhibitor that can be used in the treatment of acid-peptic-related disorders (gastroesophageal reflux disease [GERD], duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and Helicobacter pylori. Pharmacodynamic data has demonstrated that rabeprazole, with a high pKa of approximately 5.0, can be activated at a higher pH than other proton pump inhibitors. This possibly results in faster onset of action. Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less influenced by genetic polymorphisms of the CYP2C19, which others proton pump inhibitors are dependent on. In a 2-week, placebo-controlled trial, rabeprazole was both rapid and effective in relieving heartburn on day 1 of therapy and improved other GERD-related symptoms including regurgitation, belching, bloating, early satiety and nausea. For oesophageal reflux disease without erosions both 10 and 20 mg of rabeprazole are equivalent and better than placebo at 2 and 4 weeks. An on-demand approach to non-erosive reflux disease with 10 mg of rabeprazole has also been documented as superior to placebo. Some success in the treatment of extra-oesophageal manifestations of GERD, such as asthma and chronic laryngitis, has also been achieved with rabeprazole. Overall, rabeprazole with very few side effects is a safe and efficacious medication for acid suppression therapy.

Gupta A, Dawson VL, Dawson TM. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Ann Neurol. · Pubmed #19127586 No free full text.

Abstract: Currently, there is no proven neuroprotective or neurorestorative therapy for Parkinson's disease (PD). Several advances in the genetics of PD have created an opportunity to develop mechanistic-based therapies that hold particular promise for identifying agents that slow and even halt the progression of PD, as well as restore function. Here we review many of the advances in the last decade regarding the identification of new targets for the treatment of PD based on understanding the molecular mechanisms of how mutations in genes linked to PD cause neurodegeneration.

Albuquerque EX, Pereira EF, Alkondon M, Rogers SW. · Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD, USA. · Physiol Rev. · Pubmed #19126755 links to  free full text

Abstract: The classical studies of nicotine by Langley at the turn of the 20th century introduced the concept of a "receptive substance," from which the idea of a "receptor" came to light. Subsequent studies aided by the Torpedo electric organ, a rich source of muscle-type nicotinic receptors (nAChRs), and the discovery of alpha-bungarotoxin, a snake toxin that binds pseudo-irreversibly to the muscle nAChR, resulted in the muscle nAChR being the best characterized ligand-gated ion channel hitherto. With the advancement of functional and genetic studies in the late 1980s, the existence of nAChRs in the mammalian brain was confirmed and the realization that the numerous nAChR subtypes contribute to the psychoactive properties of nicotine and other drugs of abuse and to the neuropathology of various diseases, including Alzheimer's, Parkinson's, and schizophrenia, has since emerged. This review provides a comprehensive overview of these findings and the more recent revelations of the impact that the rich diversity in function and expression of this receptor family has on neuronal and nonneuronal cells throughout the body. Despite these numerous developments, our understanding of the contributions of specific neuronal nAChR subtypes to the many facets of physiology throughout the body remains in its infancy.

McGuckin J, Parkinson K. · Vascular Access Centers, Philadelphia Vascular Institute, Philadelphia, PA, USA. · Tech Vasc Interv Radiol. · Pubmed #19100949 No free full text.

Abstract: Minimally-invasive medicine has continually progressed from its beginning in the 1960's. Evolution of technology and techniques have led to treatment of new disease states in minimally-invasive therapies. Now the venue of those therapies is shifting outpatient procedures from the hospital and into outpatient centers.

Robottom BJ, Mullins RJ, Shulman LM. · Department of Neurology, University of Maryland School of Medicine, 22 South Greene Street N4W46, Baltimore, MD 21201, USA. · Expert Rev Neurother. · Pubmed #19086876 No free full text.

Abstract: Pregnancy in Parkinson's disease (PD) is an uncommon occurrence. Available reports suggest that there may be a worsening of PD symptom severity related to pregnancy. In this special report, medical literature on pregnancy in PD will be reviewed with regard to disease progression and the safety of antiparkinsonian medications. A case report of pregnancy in a woman with PD will be described. It is speculated that the symptoms of PD may be affected by changing hormone levels.

Mattson MP. · Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. · Ann N Y Acad Sci. · Pubmed #19076369 links to  free full text

Abstract: Glutamate's role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis, and neuron survival in the developing and adult mammalian nervous system. Cell-surface glutamate receptors are coupled to Ca(2+) influx and release from endoplasmic reticulum stores, which causes rapid (kinase- and protease-mediated) and delayed (transcription-dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain-derived neurotrophic factor (BDNF), which, in turn, modifies neuronal glutamate sensitivity, Ca(2+) homeostasis, and plasticity. Neurotrophic factors may modify glutamate signaling directly, by changing the expression of glutamate receptor subunits and Ca(2+)-regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy-regulating proteins, and antiapoptotic Bcl-2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer's disease to psychiatric disorders. By enhancing neurotrophic factor signaling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signaling and protect against neurological disorders.

Richter JE. · Department of Medicine, Temple University School of Medicine, 3401, North Broad Street, 801 Parkinson Pavilion, Philadelphia, PA 19140, USA. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072391 No free full text.

Abstract: Achalasia cannot be cured. Instead, our goal is to relieve symptoms of dysphagia and regurgitation, improve esophageal emptying and prevent the development of megaesophagus. The most definitive therapies are pneumatic dilation and surgical myotomy. The overall success of grade pneumatic dilation is 78%, with women and older patients performing best. Laparoscopic myotomy has an overall success rate of 85%, but can be complicated by the sequelae of severe acid reflux disease. Young patients, especially men, are the best candidates for surgical myotomy. There are no prospective, randomized studies comparing these two procedures. Botulinum toxin injections into the esophagus and smooth muscle relaxants are reserved for older patients or those with major comorbid illnesses. Some patients with end-stage achalasia will require esophagectomy.

Bras J, Singleton A, Cookson MR, Hardy J. · Molecular Genetics Unit, National Institutes on Aging, Bethesda, MD, USA. · FEBS J. · Pubmed #19021754 No free full text.

Abstract: Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis.

González-Fernández M, Daniels SK. · Department of Physical Medicine and Rehabilitation, Johns Hopkins University, School of Medicine, 600 North Wolfe Street, Phipps 174, Baltimore, MD 21287, USA. · Phys Med Rehabil Clin N Am. · Pubmed #18940646 No free full text.

Abstract: Dysphagia is a common problem in neurologic disease. The authors describe rates of dysphagia in selected neurologic diseases, and the evaluation and treatment of dysphagia in this population. Applicable physiology and aspects of neural control are reviewed. The decision-making process to determine oral feeding versus alternative means of alimentation is examined.

Maguire-Zeiss KA. · Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC 20057, United States. · Pharmacol Res. · Pubmed #18840530 No free full text.

Abstract: Parkinson's disease is a progressive age-related neurodegenerative disease with invariant loss of substantia nigra dopamine neurons and striatal projections. This disorder is well known for the associated motoric symptoms including resting tremor and the inability to initiate movement. However, it is now apparent that Parkinson's disease is a multisystem disorder with patients exhibiting symptoms derived from peripheral nervous system and extra-nigral dysfunctions in addition to the prototypical nigrostriatal damage. Although the etiology for sporadic Parkinson's disease is unknown, information gleaned from both familial forms of the disease and animal models places misfolded alpha-synuclein at the forefront. The disease is currently without a cure and most therapies target the motoric symptoms relying on increasing dopamine tone. In this review, the role of alpha-synuclein in disease pathogenesis and as a potential therapeutic target focusing on toxic conformers of this protein is considered. The addition of protofibrillar/oligomer-directed neurotherapeutics to the existing armamentarium may extend the symptom-free stage of Parkinson's disease as well as alleviate pathogenesis.

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.

Grace AA. · Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Mov Disord. · Pubmed #18781673 No free full text.

Abstract: Dopamine (DA) neurons exist in two activity states; either spontaneously firing or quiescent and nonfiring. When faced with a behavioral demand, the quiescent DA neurons can be activated to facilitate normal motor output. Levodopa appears to increase DA output by activating these nonfiring neurons; as a consequence, DA release is increased, but behavioral demand can now overwhelm the system, potentially leading to the inactivation and on/off phenomena. Levodopa administered in a pulsatile manner may also lead to the induction of synaptic plasticity within the DA systems. In the ventral mesolimbic system, this could lead to the loss of behavioral flexibility, impulsive behavior, and cognitive impairment, whereas in the dorsal nigrostriatal system, this may underlie Levodopa-induced dyskinesia. Continuous administration of Levodopa may circumvent this sensitization process, enabling a therapeutic response without limbic and motor side effects.

Vosler PS, Brennan CS, Chen J. · Department of Neurology, University of Pittsburgh School of Medicine, S-507, Biomedical Science Tower, Pittsburgh, PA 15213, USA. · Mol Neurobiol. · Pubmed #18686046 No free full text.

Abstract: Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic neuronal function. However, alterations in calcium homeostasis lead to persistent, pathologic activation of calpain in a number of neurodegenerative diseases. Pathologic activation of calpain results in the cleavage of a number of neuronal substrates that negatively affect neuronal structure and function, leading to inhibition of essential neuronal survival mechanisms. In this review, we examine the mechanistic underpinnings of calcium dysregulation resulting in calpain activation in the acute neurodegenerative diseases such as cerebral ischemia and in the chronic neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, prion-related encephalopathy, and amylotrophic lateral sclerosis. The premise of this paper is that analysis of the signaling and transcriptional consequences of calpain-mediated cleavage of its various substrates for any neurodegenerative disease can be extrapolated to all of the neurodegenerative diseases vulnerable to calcium dysregulation.

Hallett M. · Human Motor Control Section, NINDS, NIH, Bethesda, Maryland 20892-1428, USA. · Mov Disord. · Pubmed #18668625 No free full text.

Abstract: Freezing of gait appears to result from a number of fundamental problems in patients with Parkinson disease. Automaticity is impaired, putting more stress on voluntary mechanisms. Internal drivers of movement are impaired, likely because of deficient basal ganglia function. Deficiency of internal forces to initiate movement is a major factor in freezing. This deficiency gives a greater influence to external or sensory factors. The sensory factors can both help or hinder freezing. Analogous to the problem with set-shifting, there is also some difficulty in regulation of internal versus external factors and in regulation of different external factors.

Weiner WJ. · Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA. · Rev Neurol Dis. · Pubmed #18660741 No free full text.

This publication has no abstract.

Weiner WJ. · Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA. · Rev Neurol Dis. · Pubmed #18660736 No free full text.

Abstract: The diagnosis of Parkinson's disease remains a clinical diagnosis with no confirmatory laboratory or imaging studies available. The classic diagnostic criteria include 2 of 3 cardinal motor features of parkinsonism (resting tremor, cogwheel rigidity, and bradykinesia) on examination. Interest in a "premotor diagnosis" of Parkinson's disease is based on the hope that neuroprotective therapy could be initiated earlier and affect disease course. However, there is no proven method to diagnose Parkinson's disease prior to the onset of motor signs and there is no proven neuroprotective treatment. Once the diagnosis is made, the neurologist must decide, with the patient, whether to institute treatment at the time of diagnosis or whether to institute treatment when functional disability evolves. There are multiple possible initial pharmacologic choices for the initial treatment of Parkinson's disease, including monoamine oxidase type B inhibitors, dopamine receptor agonists, and levodopa/carbidopa.

Harvey BK, Wang Y, Hoffer BJ. · Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore 21224, MD, USA. · Acta Neurochir Suppl. · Pubmed #18642640 links to  free full text

Abstract: In the case of Parkinson's disease (PD), classical animal models have utilized dopaminergic neurotoxins such as 6-hydroxydopamine (6OHDA) and 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP). More recently, human genetic linkage studies have identified several genes in familial forms of PD. Transgenic models have been made that explore the function of PD-linked genes (e.g. alpha-synuclein, DJ-1, LRRK2, Parkin, UCH-L1, PINK1). Recent evidence suggests mitochondrial dysfunction may play a major role in PD. Manipulation of mitochondrial respiratory genes (e.g. mitochondrial transcription factor A or TFAM) also elicits a PD phenotype in mice. Transgenic mice (MitoPark) were developed that have TFAM selectively knocked out in dopaminergic neurons. The nigral dopamine neurons of MitoPark mice show respiratory chain dysfunction, accompanied by the development of intraneuronal inclusions and eventual cell death. In early adulthood, the MitoPark mice show a slowly progressing loss of motor function that accompanies these cellular changes. The MitoPark mouse enables further study of the role of mitochondrial dysfunction in DA neurons as an important mechanism in the development of PD. Transgenic technology has allowed new insights into mechanisms of neurodegeneration for a number of neurological disorders. This paper will summarize recent studies on several transgenic models of PD.

Moore DJ. · Institute for Cell Engineering and Department of Neurology, Johns Hopkins University School of Medicine, Broadway Research Building, 733 North Broadway, Baltimore, MD 21205, USA. · Parkinsonism Relat Disord. · Pubmed #18602856 No free full text.

Abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are an important cause of late-onset, familial and sporadic Parkinson's disease. LRRK2 is a large unique protein containing both GTPase and kinase enzymatic domains together with multiple protein-protein interaction domains. LRRK2 initially appears to function as a GTPase-regulated protein kinase. The majority of pathogenic mutations lead to enhanced kinase activity of LRRK2. Disease-associated mutations in LRRK2 also promote the formation of cytoplasmic inclusions and induce neuronal toxicity in cultured cells in a kinase-dependent manner. These and other important aspects of LRRK2 biology and pathophysiology are discussed in detail in this review.

Howland RH. · University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA. · J Psychosoc Nurs Ment Health Serv. · Pubmed #18595454 No free full text.

Abstract: Placebo and nocebo effects are interesting and complex phenomena. In this article, I discuss some findings about the psychological and neurobiological processes that may underlie these effects on the basis of studies of pain, Parkinson's disease, and depression. From a psychological perspective, expectancy and conditioning theories have been used to explain placebo and nocebo effects. These psychological processes may be translated into physiological effects through overlapping brain circuits that are important for cognitive information processing, analgesia, and reward expectations. These brain circuits may represent a fundamentally important common underlying pathway that mediates placebo and nocebo effects in many conditions. Understanding these effects is important for designing clinical treatment studies and interpreting their results and is highly relevant for clinical practices.

Sonsalla PK, Zeevalk GD, German DC. · Department of Neurology, Robert Wood Johnson Medical School/UMDNJ, 675 Hoes Lane, Piscataway, NJ 08854, USA. · Parkinsonism Relat Disord. · Pubmed #18583172 links to  free full text

Abstract: Animal models of Parkinson's disease (PD) that more closely exhibit the chronic neuropathology seen in the human condition are needed in order to reveal processes involved with progressive neurodegeneration and for testing potential interventions for retarding dopamine (DA) neuronal loss. Here we describe the recently developed chronic rat model of PD in which 1-methyl-4-phenylpyridinium ion (MPP(+)) is infused chronically into the lateral cerebral ventricle. We review features of this model that include loss of nigral DA neurons, swollen and abnormal mitochondria, striatal inclusion-like bodies and microgliosis. Advantages as well as limitations of the model are addressed.

McCall S, Vilensky JA, Gilman S, Taubenberger JK. · Department of Clinical Pathology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA. · J Neurovirol. · Pubmed #18569452 No free full text.

Abstract: Since encephalitis lethargica's (EL) prevalence in the 1920s, epidemiologic and clinical debate has persisted over whether EL was caused by, potentiated by, or merely coincident with the Spanish influenza pandemic. Epidemiologic analyses generally suggest that the disorders were coincidental. Beginning in the 1970s, modern experiments on archival brain samples mainly failed to confirm a direct relationship between influenza and EL. These experimental studies have technical limitations, e.g., the appropriateness of antibodies, polymerase chain reaction (PCR) primers and controls, and the extreme paucity and age of available material. These factors render the case against influenza less decisive than currently perceived. Nevertheless, there is little direct evidence supporting influenza in the etiology of EL. Almost 100 years after the EL epidemic, its etiology remains enigmatic, raising the possibility of a recurrence of EL in a future influenza pandemic.

Weiner WJ. · Department of Neurology, Maryland Parkinson's Disease and Movement Disorders Center, University of Maryland School of Medicine, 22 S Greene St, N4W46, Baltimore, MD 21201, USA. · Arch Neurol. · Pubmed #18541790 links to  free full text

Abstract: The term Parkinson disease defines a specific clinical condition characterized by a typical history and characteristic signs. This review examines the historical evolution of the concept of Parkinson disease and how the misunderstanding of Parkinson disease may be hindering clinical research trials. It is proposed that this syndrome be called Parkinson diseases or parkinsonism type 1 through infinity.

Wick JY, Zanni GR. · National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA. · Consult Pharm. · Pubmed #18540790 No free full text.

Abstract: Essential tremor (ET), traditionally considered benign, is a serious neurologic condition with life-altering repercussions. Its involuntary, rhythmic oscillations involve alternating, irregular, or simultaneous contractions of agonist and antagonist muscles. It is the most common of the 20 known tremor disorders and often confused with Parkinson's disease. Numerous drugs can aggravate ET, and alcohol consumption may alleviate it. Its etiology is unknown. Proven drug treatments are currently limited to propranolol and primidone. This article reviews ET with examples from history to demonstrate points.

Rothman JR, Jaffe WI. · Department of Urology, Temple University, 3401 North Broad Street, 3rd Floor, Parkinson Pavilion, Suite 350, Philadelphia, PA 19140, USA. · Curr Urol Rep. · Pubmed #18519014 No free full text.

Abstract: Prostatitis accounts for almost 2 million office visits to urologists and primary care physicians. The label "prostatitis" refers to a diverse constellation of symptoms and disease processes. The diagnosis and treatment of this disorder present numerous challenges for the physician, including a lack of abnormal findings on physical examination, laboratory tests, and radiographic images. In this article, we offer a review of the current literature and recommendations for the evaluation and diagnosis of the patient presenting with prostatitis.