Parkinson Disease: US Central Zone

Vilensky JA, Mukhamedzyanov RZ, Gilman S. · Department of Anatomy and Cell Biology, Indiana University School of Medicine, Fort Wayne, IN 46805, USA. · Eur Neurol. · Pubmed #18628628 No free full text.

Abstract: Although encephalitis lethargica (EL) appeared in epidemic form in the Soviet Union during the 1920s as it did in most of the world, the Western literature, particularly English, contains little information about the manifestations of the disease there. Here we summarize articles by prominent Russian neurologists who wrote about the disease as they viewed it during the epidemic period. As in the West, Russian clinicians found EL to be remarkably polymorphic, although some signs and symptoms, especially those pertaining to the psychological aspects of the disease, seemed to be more prevalent or were described better and perhaps more frequently by these clinicians. Some Russian clinicians emphasized an increased prevalence of EL among Jews and a relationship with illness and trauma, whereas others found strong evidence for contagion, especially in rural areas.

Thrash B, Uthayathas S, Karuppagounder SS, Suppiramaniam V, Dhanasekaran M. · Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA. · Proc West Pharmacol Soc. · Pubmed #18605226 No free full text.

Abstract: Parkinson's disease is a progressive neurological disorder associated with selective degeneration of nigrostriatal dopaminergic neurons. It is the most common of the neurodegenerative movement disorders, affecting approximately 1% of the population over age 65. Though the exact cause of the neurodegeneration is unknown, it has been shown that environmental factors can contribute to the onset of Parkinson's disease. Parkinsonian symptoms are seen following exposure to the herbicide paraquat, and the fungicide maneb. Furthermore, evidence clearly shows that neurodegeneration develops in environments where workers are co-exposed to paraquat and maneb. These neurotoxins cause a pesticide-induced loss of dopaminergic neurons, inducing a Parkinsonian phenotype. The specific mechanisms by which these environmental neurotoxins affect the nigral dopaminergic neurons are unknown. This gap in mechanistic understanding raises a need for further examination of their cytotoxic effects. Despite advances in pharmacotherapy that have improved quality of life, the mortality rate among Parkinson's disease sufferers remains largely unchanged. There is need for a proactive treatment strategy that could provide neuroprotection or neurorestoration. Since evidence has shown that environmental neurotoxins play an important role in nigral degeneration, there is obviously a need to take a closer look at such toxins since a greater understanding could aid in development of novel pharmacological agents with anti-parkinson and neuroprotective effects. In this review, we intend to examine the role of environmental toxins, namely paraquat and maneb, in the neurotoxicity that leads to dopamine depletion.

Charles PD, Gill CE, Davis TL, Konrad PE, Benabid AL. · Department of Neurology, Vanderbilt University Medical Center, A-0118 MCN, Nashville, TN 37232-2551, USA. · Nat Clin Pract Neurol. · Pubmed #18594505 No free full text.

This publication has no abstract.

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.

Meredith GE, Totterdell S, Potashkin JA, Surmeier DJ. · Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. · Parkinsonism Relat Disord. · Pubmed #18585085 links to  free full text

Abstract: Formidable challenges for Parkinson's disease (PD) research are to understand the processes underlying nigrostriatal degeneration and how to protect dopamine neurons. Fundamental research relies on good animal models that demonstrate the pathological hallmarks and motor deficits of PD. Using a chronic regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p) in mice, dopamine cell loss exceeds 60%, extracellular glutamate is elevated, cytoplasmic inclusions are formed and inflammation is chronic. Nevertheless, isradipine, an L-type calcium-channel blocker, attenuates the degeneration. These data support the validity of the MPTP/p model for unravelling the degenerative processes in PD and testing therapies that slow their progress.

Monahan AJ, Warren M, Carvey PM. · Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA. · Cell Transplant. · Pubmed #18522239 No free full text.

Abstract: Despite decades of research and the development of a large group of animal models, our understanding of the mechanisms responsible for the progressive loss of dopamine neurons in Parkinson's disease (PD) is unknown. So-called neuroprotective studies demonstrate that a vast group of molecules readily attenuate the dopamine (DA) neuron loss produced by DA neurotoxin insult. Despite these successes, these neuroprotective strategies have been surprisingly ineffective in patients. This may reflect the fact that the initial pathogenic event and the subsequent disease progression is a consequence of different mechanisms. As we began to think about this disconnect, we discovered that animals exposed to DA neurotoxins exhibited blood-brain barrier (BBB) dysfunction. If the BBB in PD patients is disrupted, then the barrier that normally segregates peripheral vascular factors from brain parenchyma is no longer present. Immune cells could then enter brain and produce a self-perpetuating (progressive) degenerative process. In this review, we propose that peripheral immunity contributes to the degenerative process of PD and may be responsible for the progressive nature of the disease. This hypothesis is supported by a broad and diverse literature that is just beginning to come together to suggest that PD is, in part, an autoimmune disease. In order to understand this hypothesis, the reader must question the conventional wisdom that the BBB is intact in PD, the brain is an immune privileged area, and that pathogenic insult and disease progression may reflect different mechanisms.

Remple MS, Sarpong Y, Neimat JS. · Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · Expert Rev Neurother. · Pubmed #18505355 No free full text.

Abstract: Despite the continued refinement of medical and surgical therapies, the treatment of Parkinson's disease (PD) remains challenging. Current treatment strategies are largely focused on managing the motor symptoms of the disease, either by dopamine-based medications or, in advanced stages, by the application of deep brain stimulation to more stably alter the function of the basal ganglia. Important advances have been made in the last decade, but unfortunately a number of the motor symptoms of late-stage PD remain poorly treated, and while currently available therapies address the symptoms of the disease, they fail to alter the course of the disease itself. This has spurred basic and clinical exploration on a number of fronts. Several centers have examined novel stimulation targets to treat refractory symptoms of gait difficulty and axial imbalance. Basic and clinical researchers are examining whether the use of deep brain stimulation might slow the progress of the disease and thus be a useful neuroprotective therapy if initiated earlier in the progression of the disease. An expanded understanding of the genetic and cellular events that underlie PD has led some researchers to explore the use of neurotrophic factors or genetic restoration to preserve threatened neuronal populations. Finally, there has been much research on the use of fetal mesencephalic or stem cell populations to restore dopaminergic function. In this report, we will examine each of these potential new surgical therapies and the promise they may hold for the future treatment of PD.

Benarroch EE. · Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. · Neurology. · Pubmed #18490619 No free full text.

This publication has no abstract.

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.

Stover NP, Watts RL. · Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. · Neurotherapeutics. · Pubmed #18394567 No free full text.

Abstract: Spheramine (Bayer Schering Pharma AG, Berlin, Germany) is currently being tested as a new approach for the treatment of Parkinson's disease (PD). It consists of an active component of cultured human retinal pigment epithelial (hRPE) cells, attached to an excipient part of cross-linked porcine gelatin microcarrriers. Spheramine is administered by stereotactic implantation into the striatum of PD patients and the use of immunosuppression is not required. Current pharmacologic therapies of PD are oriented to the administration of dopaminergic medications. Human RPE cells produce levodopa, and this constitutes the rationale to use Spheramine for the treatment of PD. The preclinical development of Spheramine included extensive biologic, pharmacologic, and toxicologic studies in vitro and in animal models of PD. The first clinical trial in humans evaluated the safety and efficacy of Spheramine implanted in the postcommissural putamen contralateral to the most affected side in six patients with advanced PD. This open-label study demonstrated good tolerability and showed sustained motor clinical improvement. A phase II double-blind, randomized, multicenter, placebo-controlled (sham surgery) study is underway to evaluate safety, tolerability, and efficacy of Spheramine implanted bilaterally into the postcommissural putamen of patients with advanced PD. Spheramine represents a treatment approach with the potential of supplying a more continuous delivery of levodopa to the striatum in advanced PD than can be achieved with oral therapy alone.

Newman MB, Bakay RA. · Department of Neurosurgery, Rush University Medical Center, Chicago, Illinois 60612, USA. · Neurotherapeutics. · Pubmed #18394566 No free full text.

Abstract: The loss of dopaminergic neurons of the substantia nigra is the pathological hallmark characteristic of Parkinson's disease (PD). The strategy of replacing these degenerating neurons with other cells that produce dopamine has been the main approach in the cell transplantation field for PD research. The isolation, differentiation, and long-term cultivation of human embryonic stem cells and the therapeutic research discovery made in relation to the beneficial properties of neurotrophic and neural growth factors has advanced the transplantation field beyond dopamine-producing cells. The present review addresses recent advances in human embryonic stem cell experimentation in relation to treating PD, as well as cell transplantation techniques in conjunction with alternative therapeutics.

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.

Miller RL, James-Kracke M, Sun GY, Sun AY. · Department of Medical Pharmacology and Physiology, University of Missouri - Columbia, Columbia, MO, 65212, USA. · Neurochem Res. · Pubmed #18363100 No free full text.

Abstract: Parkinson's disease (PD) is the second most prevalent age-related neurodegenerative disease with physiological manifestations including tremors, bradykinesia, abnormal postural reflexes, rigidity and akinesia and pathological landmarks showing losses of dopaminergic neurons in the substantia nigra. Although the etiology of PD has been intensively pursued for several decades, biochemical mechanisms and genetic and epigenetic factors leading to initiation and progression of the disease remain elusive. Environmental toxins including (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) MPTP, paraquat and rotenone have been shown to increase the risk of PD in humans. Oxidative stress remains the leading theory for explaining progression of PD. Studies with cell and animal models reveal oxidative and inflammatory properties of these toxins and their ability to activate glial cells which subsequently destroy neighboring dopaminergic neurons. This review describes pathological effects of neurotoxins on cells and signaling pathways for production of reactive oxygen species (ROS) that underline the pathophysiology of PD.

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.

Farlow MR, Cummings J. · Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Dement Geriatr Cogn Disord. · Pubmed #18311077 No free full text.

Abstract: BACKGROUND/AIMS: Parkinson's disease dementia (PDD) is common, but its neuropathological basis has been controversial. The aim of this review was to survey the recent literature on the pathology of PDD and compare the pathology of PDD to that of Alzheimer's disease (AD). METHODS: A literature search was performed to identify relevant research published since 2001. RESULTS: There is widespread Lewy body pathology in the neocortex and subcortical regions in PDD, and Lewy neurites in the CA2 region of the hippocampus that correlate with cognitive decline. Genetic forms of PD, which frequently lead to dementia, are associated with deposition of alpha-synuclein; PDD is not related to the apolipoprotein E epsilon 4 genotype. Compared with AD, central cholinergic deficits occur earlier, are greater and more widespread in PDD, but PDD can occur without the abundant senile plaques and neurofibrillary tangles indicative of AD. CONCLUSION: Epidemiological investigations, neuroimaging, as well as genetic and neuropathological studies increasingly support PDD as distinct from AD.

Meredith GE, Sonsalla PK, Chesselet MF. · Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. · Acta Neuropathol. · Pubmed #18273623 links to  free full text

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is not understood. This disease occurs both sporadically and through inheritance of single genes, although the familial types are rare. Over the past decade or so, experimental and clinical data suggest that PD could be a multifactorial, neurodegenerative disease that involves strong interactions between the environment and genetic predisposition. Our understanding of the pathophysiology and motor deficits of the disease relies heavily on fundamental research on animal models and the last few years have seen an explosion of toxin-, inflammation-induced and genetically manipulated models. The insight gained from the use of such models has strongly advanced our understanding of the progression and stages of the disease. The models have also aided the development of novel therapies to improve symptomatic management, and they are critical for the development of neuroprotective strategies. This review critically evaluates these in vivo models and the roles they play in mimicking the progression of PD.

Xie X, Ramkumar V, Toth LA. · Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA. · Comp Med. · Pubmed #18246865 No free full text.

Abstract: This review will examine how dopamine, a monoamine neurotransmitter, and adenosine, a neuromodulator, regulate behavioral activation, primarily as reflected by locomotor activity, in rodents. Complex interactions among 2 major types of adenosine receptors (A1AR and A2AAR) and 2 dopamine receptors (D1R and D2R) occur due to physical interactions that alter their ligand-binding properties and subsequent effects on common postreceptor signaling molecules. The output from these interactions in striatum modulates neurotransmission and subsequently influences spontaneous locomotor activity. Caffeine is a nonselective adenosine receptor antagonist that blocks 2 major types of adenosine receptors, A1AR and A2AAR, in the brain. Pharmacologic manipulation of these receptors with drugs such as caffeine offers potential therapeutic benefit for treatment of Parkinson disease.

Freeman JW, Simmons M, Matos E. · Department of Neurosciences, Sanford School of Medicine of The University of South Dakota, USA. · S D Med. · Pubmed #18232251 No free full text.

This publication has no abstract.

Karamyan VT, Speth RC. · Department of Pharmacology, School of Pharmacy, University of Mississippi, MS 38677, USA. · Life Sci. · Pubmed #18191417 No free full text.

Abstract: Of all the molecules reported to have toxicological effects, BMAA (beta-methylamino alanine) stands out as having the most checkered past. In the late 1960's it was reported to be a toxic component of the cycad flour consumed by Chamorros on Guam which caused the high incidence of amyotrophic lateral sclerosis (ALS) in Guam, that was associated with a Parkinson's disease-like dementia complex (ALS-PDC). However, because ALS-PDC is a slow onset disease, manifesting itself as long as 30 years following exposure to the putative neurotoxin, and only acute toxic effects of BMAA were observed in animal studies, interest in BMAA waned. A seminal study by Spencer et al., in 1987 showing neurological impairments with long-term BMAA-fed monkeys revived the hypothesis that BMAA could cause ALS-PDC. However, the amounts of BMAA used in that study were viewed as being the equivalent of a person consuming their body weight of cycad flour every day. Again, the BMAA hypothesis was discarded. Recently a third iteration of the BMAA hypothesis has been proposed. It is based on the discovery of a novel dietary source of BMAA via biomagnification of BMAA in flying foxes, once consumed in great amounts by Chamorros. Also, reports that BMAA can be incorporated into plant and animal proteins, a heretofore unrecognized dietary source of BMAA, further solidified this new hypothesis. However, once again this hypothesis has its detractors and it remains controversial. This manuscript critically evaluates in vivo studies directed at establishing an animal model of BMAA-induced ALS-PDC and their implications for this hypothesis.

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.

Comella CL. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #18175398 No free full text.

Abstract: Sleep disturbances are one of the most common of the nonmotor complications of Parkinson's disease (PD), and increase in frequency with advancing disease. The causes of sleep disturbance in PD are numerous, and many patients may have several factors that contribute. These disorders can be broadly categorized into those that involve nocturnal sleep and daytime manifestations such as excessive daytime sleepiness. Some sleep disorders, in particular REM sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS) may arise as a primary manifestation of PD, reflecting the anatomic areas affected by the neurodegenerative process. Appropriate diagnosis of the sleep disturbance affecting a PD patient can lead to specific treatments that can consolidate nocturnal sleep and enhance daytime alertness.

Yu H, Neimat JS. · Department of Neurological Surgery, Vanderbilt University, Nashville, Tennessee 37232, USA. · Neurotherapeutics. · Pubmed #18164481 No free full text.

Abstract: It has been understood, for some time, that modulation of deep brain nuclei within the basal ganglia and thalamus can have a therapeutic effect in patients with movement disorders. Because of its reversibility and adjustability, deep brain stimulation (DBS) has largely come to replace traditional ablation procedures. The clinical effects of DBS vary, depending both on the target being stimulated and on the parameters of stimulation. Both aspects are currently the subject of substantial research and discovery. The most common targets for DBS treatment include the subthalamic nucleus for the treatment of advanced Parkinson's disease, the ventral intermediate nucleus of the thalamus for the treatment of medically refractory essential tremor, and the globus pallidus interna for the treatment of both cervical and generalized dystonias and Parkinson's disease. We review the current indications, targets, outcomes, and general procedure of DBS for essential tremor, Parkinson's disease, and dystonia.

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.

Pankratz N, Foroud T. · Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-3002, USA. · Genet Med. · Pubmed #18091429 No free full text.

Abstract: During the past decade five genes have been identified that are important in autosomal dominant and autosomal recessive forms of Parkinson disease. The identification of these genes has increased our understanding of the likely pathogenic mechanisms resulting in disease. However, mutations in these genes likely contribute to disease in fewer than 5% of all cases of Parkinson disease. Thus, researchers have continued to search for genes that may influence disease susceptibility. Molecular diagnostic testing is currently available for four of the genes mutated in Parkinson disease. Evidence for reduced penetrance, possible effects of haploinsufficiency, and the identification of nondisease causing polymorphisms within several of these genes has made genetic counseling challenging. Current recommendations are to limit molecular testing only to those individuals who are symptomatic. Furthermore, because treatment is unaltered by the presence or absence of mutations in these genes, restraint is recommended when considering the value of screening for mutations in a clinical setting.