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  1. Secondary parkinsonism

    MedlinePlus

    Parkinsonism - secondary; Atypical Parkinson disease ... to be less responsive to medical therapy than Parkinson disease. ... Unlike Parkinson disease, some types of secondary parkinsonism may stabilize or even improve if the underlying cause is treated. ...

  2. Secondary parkinsonism

    MedlinePlus

    Parkinsonism - secondary; Atypical Parkinson disease ... to be less responsive to medical therapy than Parkinson disease. ... Unlike Parkinson disease, some types of secondary parkinsonism may stabilize or even improve if the underlying cause is treated. Brain ...

  3. Parkinson disease

    MedlinePlus

    American Parkinson Disease Association. Parkinson's Disease Handbook: A Guide for Patients and Their Families. Revised 2009. Available at: www.apdaparkinson.org/uploads/files/MP51919AmParkinsonHBK-vaU.pdf . Accessed September 15, ...

  4. Parkinson's Disease

    MedlinePlus

    ... results in reduction of a critical neurotransmitter called dopamine, a chemical responsible for transmitting messages to parts ... that coordinate muscle movement. Parkinson's patients have less dopamine. Studies have shown that the symptoms of Parkinson's ...

  5. Parkinson's Disease

    MedlinePlus

    ... about 5 to 10 percent of people with Parkinson's have "early-onset" disease which begins before the age of 50. Early-onset forms of Parkinson's are often inherited, though not always, and some ...

  6. Unraveling Parkinson's: Three Clues

    MedlinePlus

    ... Bar Home Current Issue Past Issues Unraveling Parkinson's: Three Clues Past Issues / Summer 2006 Table of Contents ... Dream Robber: Living with Parkinson's disease / Unraveling Parkinson's: Three Clues / Parkinson's Disease: The Newest Advances Summer 2006 ...

  7. Parkinson's Disease

    MedlinePlus

    Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...

  8. Parkinson disease

    MedlinePlus

    Nerve cells use a brain chemical called dopamine to help control muscle movement. With Parkinson disease, the brain cells that make dopamine slowly die. Without dopamine, the cells that control movement ...

  9. Parkinson's Disease

    MedlinePlus

    ... cells make and use a brain chemical called dopamine (say: DOH-puh-meen) to send messages to ... coordinate body movements. When someone has Parkinson's disease, dopamine levels are low. So, the body doesn't ...

  10. Hitler's parkinsonism.

    PubMed

    Boettcher, Lillian B; Bonney, Phillip A; Smitherman, Adam D; Sughrue, Michael E

    2015-07-01

    Of the multitude of medical and psychiatric conditions ascribed to Hitler both in his lifetime and since his suicide in April 1945, few are more substantiated than parkinsonism. While the timeline of the development of this condition, as well as its etiology, are debated, there is clear evidence for classic manifestations of the disease, most prominently a resting tremor but also stooped posture, bradykinesia, micrographia, and masked facial expressions, with progression steadily seen over his final years. Though ultimately speculation, some have suggested that Hitler suffered from progressive cognitive and mood disturbances, possibly due to parkinsonism, that affected the course of events in the war. Here, the authors discuss Hitler's parkinsonism in the context of the Third Reich and its eventual destruction, maintaining that ultimately his disease had little effect on the end result. PMID:26126407

  11. Viral Parkinsonism

    PubMed Central

    Jang, Haeman; Boltz, David A.; Webster, Robert G.; Smeyne, Richard Jay

    2015-01-01

    Parkinson's disease is a debilitating neurological disorder characterized that affects 1-2% of the adult population over 55 years of age. For the vast majority of cases, the etiology of this disorder is unknown, although it is generally accepted that there is a genetic susceptibility to any number of environmental agents. One such agent may be viruses. It has been shown that numerous viruses can enter the nervous system, i.e. they are neurotropic, and induce a number of encephalopathies. One of the secondary consequences of these encephalopathies can be parkinsonism, that is both transient as well as permanent. One of the most highlighted and controversial cases of viral parkinsonism is that which followed the 1918 influenza outbreak and the subsequent induction of von Economo's encephalopathy. In this review, we discuss the neurological sequelae of infection by influenza virus as well as that of other viruses known to induce parkinsonism including Coxsackie, Japanese encephalitis B, St. Louis, West Nile and HIV viruses. PMID:18760350

  12. Parkinson Disease.

    PubMed

    Capriotti, Teri; Terzakis, Kristina

    2016-06-01

    Parkinson disease (PD) is a progressive neurodegenerative disease that affects one million people in the United States. This article reviews the etiology and pathophysiology of PD, risk factors, clinical manifestations, diagnostic criteria, and treatment of this common disease. Implications for home care clinicians are included. PMID:27243427

  13. Progression of Parkinson's Disease

    MedlinePlus

    ... National HelpLine Educational Publications Online Seminars Parkinson's News Parkinson's HelpLine Learn More Educational Materials Do you want ... out daily activities, and treatment complications. Severity of Parkinson's Below are some descriptions of mild, moderate and ...

  14. Parkinson's Disease Foundation

    MedlinePlus

    ... Parkinson’s View All News PDF at the 4th World Parkinson Congress Tuesday, September 20-Friday, September 23 ... the Parkinson's Disease Foundation (PDF) at the 4th World Parkinson Congress, a gathering of the international Parkinson’s ...

  15. [Vascular parkinsonism].

    PubMed

    Yamanouchi, H

    1997-01-01

    Critchley speculated that multiple vascular lesions of the basal ganglia must have an etiological connection to the symptoms of so-called vascular parkinsonism (VP), but without neuropathological confirmation. Some had doubts about its existence because of the lack of the pathologically confirmed case with adequate clinical correlation. At present, VP is characterized clinically by the short-stepped or frozen gait, lead-pipe rigidity, the symmetry of findings, absence of resting tremor, and negative response to levodopa in elderly patients with cerebrovascular lesions on CT/MRI. Pseudobulbar palsies, pyramidal tract findings, and/or multi-infarct dementia coexist in some of the cases. Most of clinically suspected VP patients have cerebral white matter lesions as well as basal ganglia lesions. PMID:9014431

  16. Symptoms of Parkinson's

    MedlinePlus

    ... HelpLine Educational Publications Online Seminars Parkinson's News Educational Materials Do you need to know more about Parkinson's? PDF's materials provide information about symptoms, medications, resources & more. Order ...

  17. Managing Your Parkinson's Disease

    MedlinePlus

    ... Team Finding Resources Parkinson's HelpLine Learn More Educational Materials Do you want to know more about Parkinson's? PDF's materials provide information about symptoms, medications, resources & more. Order ...

  18. Parkinson disease - resources

    MedlinePlus

    Resources - Parkinson disease ... The following organizations are good resources for information on Parkinson disease : The Michael J. Fox Foundation -- www.michaeljfox.org National Institute of Neurological Disorders and Stroke -- www. ...

  19. Parkinson disease - discharge

    MedlinePlus

    Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads ... have you take different medicines to treat your Parkinson disease and many of the problems that may ...

  20. Parkinson disease - discharge

    MedlinePlus

    Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads to ... have you take different medicines to treat your Parkinson disease and many of the problems that may come ...

  1. Welding and parkinsonism.

    PubMed

    Furbee, Brent

    2011-08-01

    Manganese-induced parkinsonism has been recognized since 1837. It has been reported primarily in miners, grinders, and smelters since that time. More recently, isolated case reports involving welders have appeared in the medical literature. Manganism can be distinguished from other forms of parkinsonism by clinical presentation with support from laboratory and radiologic findings. The controversy regarding the risk of parkinsonism in welders is reviewed. PMID:21803214

  2. Parkinson's disease with camptocormia

    PubMed Central

    Bloch, F; Houeto, J L; du Montcel, S Tezenas; Bonneville, F; Etchepare, F; Welter, M L; Rivaud‐Pechoux, S; Hahn‐Barma, V; Maisonobe, T; Behar, C; Lazennec, J Y; Kurys, E; Arnulf, I; Bonnet, A M; Agid, Y

    2006-01-01

    Background Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position. The origin of the disorder is unknown, but it is usually attributed either to a primary or a secondary paravertebral muscle myopathy or a motor neurone disorder. Camptocormia is also observed in a minority of patients with parkinsonism. Objective To characterise the clinical and electrophysiological features of camptocormia and parkinsonian symptoms in patients with Parkinson's disease and camptocormia compared with patients with Parkinson's disease without camptocormia. Methods Patients with parkinsonism and camptocormia (excluding patients with multiple system atrophy) prospectively underwent a multidisciplinary clinical (neurological, neuropsychological, psychological, rheumatological) and neurophysiological (electromyogram, ocular movement recording) examination and were compared with age‐matched patients with Parkinson's disease without camptocormia. Results The camptocormia developed after 8.5 (SD 5.3) years of parkinsonism, responded poorly to levodopa treatment (20%) and displayed features consistent with axial dystonia. Patients with camptocormia were characterised by prominent levodopa‐unresponsive axial symptoms (ie, axial rigidity, gait disorder and postural instability), along with a tendency for greater error in the antisaccade paradigm. Conclusion We suggest that (1) the salient features of parkinsonism observed in patients with camptocormia are likely to represent a specific form of Parkinson's disease and camptocormia is an axial dystonia and (2) both camptocormia and parkinsonism in these patients might result from additional, non‐dopaminergic neuronal dysfunction in the basal ganglia. PMID:16754693

  3. Hereditary Parkinson s Disease Natural History Protocol

    ClinicalTrials.gov

    2016-08-31

    Parkinson Disease 6, Early-Onset; Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human; Parkinson Disease Autosomal Recessive, Early Onset; Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1

  4. Parkinson's Disease Foundation Newsletter

    MedlinePlus

    ... Newsletters These include monthly e-newsletters and quarterly science-specific e-newsletters. Read the latest issue below or browse the archives. National Parkinson Foundation and the Parkinson’s Disease Foundation Complete Merger to ...

  5. [Depression in Parkinson's disease].

    PubMed

    Murata, Miho; Okamoto, Tomoko

    2013-01-01

    The frequency of depression in patients with Parkinson's disease is approximately 30-40%. Depression has a significantly negative impact on the QOL in Parkinson's disease patients. It leads to the worsening of tremors and frozen gait without disease progression and decreases the patient's motivation to participate in rehabilitation. The distinguishing feature of depression in patients with Parkinson's disease is that guilt, self-blame and suicidal ideation are rarely seen compared to that observed in patients with major depression. Depression can occur in the pre-motor, diagnostic and advanced stages of Parkinson's disease. In particular, patients with wearing-off symptoms are apt to develop anxiety. As for treatment, it is very important to optimize dopamine replacement therapy. Antiparkinsonian drugs may have beneficial effects not only on the motor symptoms of the disease, but also the patient's mood. Cognitive behavioral therapy (CBT) and peer counseling may also be beneficial. PMID:24622217

  6. [The Parkinson puzzle].

    PubMed

    Guseo, András

    2012-12-30

    Parkinson's disease is one of the most frequent progressive degenerative disorders with unknown origin of the nervous system. The commutation of the disease on Guam led to the discovery of a neurotoxin which was also found in other continents. This neurotoxin was identified in the common cyanobacteria (blue-green algae). Early clinical observations suggested some loose correlations with gastric and duodenal ulcer and Parkinson's disease, while recent studies revealed a toxin, almost identical to that found in cyanobacteria in one strain of Helicobacter pylori, which proved to cause Parkinson like symptoms in animals. Therefore, it cannot be ruled out that there is a slowly progressive poisoning in Parkinson's disease. The disease specific alpha-sinuclein inclusions can be found in nerve cells of the intestinal mucosa far before the appearance of clinical symptoms indicating that the disease may start in the intestines. These results are strengthened by the results of Borody's fecal transplants, after which in Parkinson patients showed a symptomatic improvement. Based on these observations the Parkinson puzzle is getting complete. Although these observations are not evidence based, they may indicate a new way for basic clinical research, as well as a new way of thinking for clinicians. These new observations in psycho-neuro-immunology strengthen the fact that immunological factors may also play a critical factor facilitating local cell necrosis which may be influenced easily. PMID:23261994

  7. Wolff-Parkinson-White syndrome

    MedlinePlus

    Wolff-Parkinson-White syndrome is a condition in which there is an extra electrical pathway of the heart. The ... to periods of rapid heart rate ( tachycardia ). Wolff-Parkinson-White syndrome is one of the most common ...

  8. How Is Parkinson's Disease Treated?

    MedlinePlus

    ... can help make life better for people with Parkinson's General Gift Tribute Gift Moving Day ® Team Hope ... can help make life better for people with Parkinson's General Gift Tribute Gift Moving Day ® Team Hope ...

  9. Parkinson's disease and the skin.

    PubMed

    Gregory, Ralph; Miller, Sarah

    2015-08-01

    The concept that the skin is a mirror of Parkinson's disease dates to the start of the last century. Despite dermatological disorders being recognised as a common non-motor symptom of Parkinson's disease, they are often overlooked. This article reviews the various skin disorders seen in Parkinson's disease and addresses the other dermatological questions that are frequently raised by those attending Parkinson's disease clinics. PMID:25862733

  10. Protagonists with Parkinson's disease.

    PubMed

    Haan, Joost

    2013-01-01

    Parkinson's disease is a complex disorder with many fascinating features. Its onset is creeping, the progression is slow but inevitable. There are motor symptoms, such as a tremor, rigidity, bradykinesia, mask-like facial expression, and postural abnormalities, but also hallucinations, cognitive deterioration, and depression. In many novels, fictive patients with Parkinson's disease play a role. It seems that authors have used many aspects of the disease to emphasize their messages. Their narratives include themes such as rigidity, petrifaction, confusion, dementia, and hallucinations. In this chapter, as examples, several protagonists with Parkinson's disease will be described from works of John Updike, Jonathan Franzen, Sue Miller, J.M. Coetzee, and John Harding, among others. PMID:23485900

  11. Parkinson Disease and Dementia.

    PubMed

    Garcia-Ptacek, Sara; Kramberger, Milica G

    2016-09-01

    Dementia is a frequent complication of Parkinson disease (PD) with a yearly incidence of around 10% of patients with PD. Lewy body pathology is the most important factor in the development of Parkinson disease dementia (PDD) and there is evidence for a synergistic effect with β-amyloid. The clinical phenotype in PDD extends beyond the dysexecutive syndrome that is often present in early PD and encompasses deficits in recognition memory, attention, and visual perception. Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are often present. This review provides an update on current knowledge of PDD including aspects of epidemiology, pathology, clinical presentation, management, and prognosis. PMID:27502301

  12. Living with Parkinson's

    MedlinePlus

    ... Tips from the Health Care Team Finding Resources Parkinson's HelpLine Learn More Educational Materials Do you want ... resources & more. Order Free Materials Today Living with Parkinson’s “Parkinson’s is a part of my life, but ...

  13. Imaging in Parkinson's disease.

    PubMed

    Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

    2016-08-01

    The clinical presentation of Parkinson's disease (PD) is heterogeneous and overlaps with other conditions, including the parkinsonian variant of multiple system atrophy (MSA-P), progressive supranuclear palsy (PSP) and essential tremor. Imaging of the brain in patients with parkinsonism has the ability to increase the accuracy of differential diagnosis. Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) allow brain imaging of structural, functional and molecular changes in vivo in patients with PD. Structural MRI is useful to differentiate PD from secondary and atypical forms of parkinsonism. 123I-ioflupane (DaTSCAN(TM)) SPECT is a valid tool in the differential diagnosis between PD and non-degenerative tremors, while cardiac 123I-metaiodobenzylguanidine SPECT and 18F-fluorodeoxyglucose PET are valid in the differential diagnosis between PD and atypical parkinsonism (MSA-P, PSP). However, despite significant evidence for the utility of neuroimaging in assessing parkinsonian patients, none of the neuroimaging techniques are specifically recommended for routine use in clinical practice. Hopefully, future larger trials will help to demonstrate additional evidence for the clinical utility of neuroimaging and will include an analysis of the financial benefits for the NHS in the longer term management of the patients. PMID:27481384

  14. Young-Onset Parkinson's

    MedlinePlus

    ... idiopathic, or typical, PD. Understanding the roles of environment and genes will ultimately allow us to identify the multiple causes of PD. Is Medication Treatment Different for Young-Onset PD? Medical management of young-onset Parkinson's disease requires an understanding ...

  15. Parkinson's Disease Research Web - Information for Patients and Caregivers

    MedlinePlus

    ... Find People About NINDS Parkinson's Disease Research Web - Information for Patients & Caregivers Parkinson's Disease Highlights for Patients & ... and progression biomarkers for PD. NINDS Parkinson's Disease Information Parkinson's Disease Information Page Parkinson's Disease: Hope Through ...

  16. Vascular parkinsonism: Deconstructing a syndrome

    PubMed Central

    Vizcarra, Joaquin A.; Lang, Anthony E.; Sethi, Kapil D; Espay, Alberto J.

    2015-01-01

    Progressive ambulatory impairment and abnormal white matter signal on neuroimaging come together under the diagnostic umbrella of vascular parkinsonism. A critical appraisal of the literature, however, suggests that (1) no abnormal structural imaging pattern is specific to vascular parkinsonism; (2) there is poor correlation between brain magnetic resonance imaging hyperintensities and microangiopathic brain disease and parkinsonism from available clinicopathologic data; (3) pure parkinsonism from vascular injury (“definite” vascular parkinsonism) consistently results from ischemic or hemorrhagic strokes involving the substantia nigra and/or nigrostriatal pathway but sparing the striatum itself, the cortex, and the intervening white matter; and (4) many cases reported as vascular parkinsonism may represent pseudovascular parkinsonism (e.g., Parkinson disease or another neurodegenerative parkinsonism such as progressive supranuclear palsy with non-specific neuroimaging signal abnormalities), vascular pseudoparkinsonism (e.g., akinetic mutism due to bilateral mesial frontal strokes or apathetic depression from bilateral striatal lacunar strokes), or pseudovascular pseudoparkinsonism (e.g., higher-level gait disorders, including normal pressure hydrocephalus with transependimal exudate). These syndromic designations are preferable over vascular parkinsonism until pathology or validated biomarkers confirm the underlying nature and relevance of the leukoaraiosis. PMID:25997420

  17. Micrographia in Parkinson's disease.

    PubMed

    Contreras-Vidal, J L; Teulings, H L; Stelmach, G E

    1995-10-23

    A computational neural model of movement production in normal and Parkinson's disease (PD) is used to provide a neural account for the source of micrographia in PD handwriting. It is hypothesized that smaller than normal pallido-thalamic signals, due to dopamine depletion, are responsible for the observed overall smallness, slowness and variability in PD handwriting. Experimental data from PD patients that show micrographia support this hypothesis and imply the functional segregation of basal ganglia neural populations. PMID:8580447

  18. [Parkinson disease and communication].

    PubMed

    Barat, M; Daverat, P; Mazaux, J M

    1992-01-01

    Communication abilities imply multifactorial analysis. These disorders in Parkinson's disease involve speech, graphism, functional and paraverbal gestures. The patient's isolation in a major form of disease is dramatic. Functional study requires an analysis of each factor; progress should be realized for an objective approach. With a therapeutic objective in view, the most impaired features, and the patients real situation and way of life must be evaluated. Some training measures are useful especially for social adjustment and motivational reinforcement. PMID:1344546

  19. Methamphetamine and Parkinson's Disease

    PubMed Central

    Granado, Noelia; Ares-Santos, Sara; Moratalla, Rosario

    2013-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles. PMID:23476887

  20. Parkinson's disease and insomnia.

    PubMed

    Ylikoski, Ari; Martikainen, Kirsti; Sieminski, Mariusz; Partinen, Markku

    2015-11-01

    There is a broad spectrum of sleep disturbances observed in Parkinson's disease (PD). The prevalence of symptoms of insomnia and chronic inability to sleep and their association with other sleep disorders were studied. Altogether 1447 randomly selected Parkinson patients, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep questionnaire. Questions on demographics, PD, REM Sleep Behavior Disorder, and other issues were included. The response rate was 59 % (N = 854), and of these 81 % returned fully answered questionnaire (N = 689). Prevalence of chronic inability to sleep was 36.9 % (95 % CI 33.3-40.5). Difficulty of initiating sleep was 18.0 % (95 % CI 15.1-20.9), disrupted sleep 81.54 % (78.5-84.4), awakenings during night 31.3 % (27.8-34.8), early morning awakenings 40.4 % (36.8-44.1) and non-restorative sleep 38.5 % (34.8-42.1). In the logistic regression models, poor quality of life and restless legs syndrome correlated significantly with chronic insomnia disorder. Disrupted sleep and early morning awakenings were the most common insomnia symptoms. PD patients do not seem to have difficulties in sleep initiation. Insomnia symptoms including disruptive sleep and non-restorative sleep are common in patients with Parkinson's disease. Inability to sleep is more common as comorbidity than a single sleep problem. PMID:26099862

  1. [Parkinson's disease and psychoses].

    PubMed

    Bizzarri, Jacopo Vittoriano; Giupponi, Giancarlo; Maniscalco, Ignazio; Schroffenegger, Patrizia; Conca, Andreas; Kapfhammer, Hans Peter

    2015-01-01

    Psychotic symptoms are common in Parkinson's disease (PD) and are associated with increased disability, worsened quality of life, and poor long-term prognosis. In this article, clinical features, hypotheses on pathogenesis, and current treatment strategies for Parkinson's disease psychosis (PDP) are reviewed. According to epidemiological studies, the prevalence of PDP is between 20 to 40 %. Complex visual hallucinations are the most common psychotic symptoms and are present in 17-72 % of the patients. Other sensory disturbances encompass tactile hallucinations and minor hallucinatory phenomena, such as sense of presence and visual illusions. Hallucinations are often accompanied by delusions, whose most frequent themes are persecution and jealousy. The pathophysiology of PDP remains unclear. Different factors have been implicated, including Levo-dopa and dopaminergic medications, neurotransmitter imbalances, neuroanatomic alterations, abnormal visuospatial processes, and genetic predisposition. The first-line strategy in the treatment of persistent and problematic PDP is represented by reduction in anti-PD medications. Second-generation antipsychotics are the treatment of choice, with clozapine being demonstrated as the most effective and tolerable drug for PD patients. PMID:25586068

  2. Parkinson's disease tremor: pathophysiology.

    PubMed

    Hallett, Mark

    2012-01-01

    There are a number of tremors that may affect patients with Parkinson's disease, but the classic is tremor-at-rest. The tremor is also seen during postural action after a short pause, and is often called re-emergent tremor although it appears that the physiology is the same. As a manifestation of Parkinson's disease, it is separate from bradykinesia and rigidity as the magnitude of tremor is not related to dopamine deficiency nor does it respond readily to dopamine treatment. Cellular activity in the different basal ganglia nuclei can be coherent with tremor, but cellular activity in the VIM nucleus of the thalamus, a cerebellar relay nucleus, is more coherent than cellular activity in basal ganglia. It is also notable that different body parts may have similar tremor frequencies, but are generally not exactly the same and are not phase locked. This suggests that each body part has a separate tremor generator. The ability to stay separate may be due to the somatotopic segregation of basal ganglia loops. Analysis of cellular behavior in the thalamus shows that the thalamus is not the generator of tremor. New data suggest that the basal ganglia trigger a cerebellar circuit to produce the tremor. PMID:22166464

  3. Genetic susceptibility variants in parkinsonism.

    PubMed

    Soto-Ortolaza, Alexandra I; Ross, Owen A

    2016-01-01

    Parkinsonism is an umbrella term for a group of disorders characterized by the clinical signs of tremor, bradykinesia, rigidity, and postural instability. On neuropathologic examination parkinsonism can display alternate protein pathologies (e.g. α-synucleinopathy or tauopathy) but the degeneration of nigral neurons is consistent. The main forms of parkinsonism are, Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). Genetic studies from candidate gene, to unbiased genome-wide approaches including association and next-generation sequencing have nominated a number of disease determinants. Within this review we will highlight the genetic loci that are associated with disease and discuss the implications and importance for a better understanding of the genes involved and thus the underlying pathophysiology of these disorders. PMID:26414118

  4. Cognitive impairment in Parkinson's disease.

    PubMed

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy. PMID:26609664

  5. [Initial symptomatology of Parkinson disease].

    PubMed

    Fuhr, P; Maritz, D; Bernatik, J; Steck, A J

    1995-01-01

    The early diagnosis of Parkinson's disease (idiopathic parkinsonism) is important for two reasons. Some never drugs possibly have a neuroprotective effect, which can be utilized maximally only with early onset of treatment. Moreover, diagnostic mistakes may occur early in the course of the disease. Although the hallmark of Parkinson's disease is a syndrome of movement disorders, slight cognitive deficits, depression, or pain with or without paresthesias can be present at an early stage. Therefore, symptoms at the time of the first diagnosis and at the beginning of the first clinical manifestation of Parkinson's disease are often not identical. The diagnosis can be made only clinically, since no biological marker is available up to now. However, in unclear cases pharmacological tests constitute a valuable extension of the clinical examination. PMID:8533059

  6. Genetics Home Reference: Parkinson disease

    MedlinePlus

    ... Many Parkinson disease symptoms occur when nerve cells (neurons) in the substantia nigra die or become impaired. ... produce smooth physical movements. When these dopamine-producing neurons are damaged or die, communication between the brain ...

  7. [Biotherapies and Parkinson's disease].

    PubMed

    Cesaro, P; Fenelon, G; Remy, P

    2009-11-01

    In the last years, several experimental biotherapies have been developed to treat Parkinson's disease. Initially, fetal dopaminergic transplants were proposed. Although a proof of concept and encouraging results have been provided, limitations of this treatment emerged over the years and the failure of controlled trials have conducted to a pause in the development of strategies based on fetal cells. Alternative approaches such as the use of retinal pigmented cells recently provided disappointing results in patients and much hope has now been reported on other sources of dopaminergic neurons such as those originating from stem cells. This strategy is however not yet ready for clinical trials in patients. Eventually, gene therapy is a new original experimental technique which has elicited several trials in the last few years some of them being promising. PMID:19487002

  8. Homotaurine in Parkinson's disease.

    PubMed

    Ricciardi, Lucia; De Nigris, Francesca; Specchia, Alessandro; Fasano, Alfonso

    2015-09-01

    Homotaurine is a natural compound of red algae, which has been demonstrated to have a neuroprotective effect and has been evaluated as a possible therapeutic agent for Alzheimer's disease. This was a single blind, randomized, controlled study to evaluate the safety and efficacy of homotaurine in patients with Parkinson's disease (PD) and cognitive impairment. Patients were evaluated at baseline and 6 months later. Assessments included, the evaluation of: motor and non-motor conditions and complications (Unified Parkinson's Disease Rating Scale, UPDRS); disability and quality of life; depression; excessive daytime sleepiness and fatigue. An extensive neuropsychological tests battery was administered evaluating specific cognitive domains: memory, phonemic verbal fluency, executive functions and selective visual attention. After baseline testing, patients were allocated to one of the two groups: (A) treatment group: patients treated with homotaurine 100 mg; (B) control group: patients not treated with homotaurine. Forty-seven patients were evaluated at baseline, 24 (51 %) completed the study (PD-homotaurine: n = 11; 44 % and PD-controls: n = 13; 59 %); discontinuation rate was similar across subjects (p = 1.0). Intention to treat analyses to evaluate homotaurine safety showed mild side effects (gastrointestinal upsetting) in 3 patients. Per protocol analyses of homotaurine efficacy showed no difference between groups. Within group analyses showed that PD-homotaurine patients had better score at UPDRS-I at the end of the study compared to baseline (p = 0.017) and at Epworth Sleepiness Scale (p = 0.01). No other differences were found. No significant difference arose for the PD-ctrl group. Homotaurine is a safe drug. Our data suggest a beneficial effect of homotaurine on excessive sleepiness. Future studies are encouraged to confirm this promising role of homotaurine in promoting the sleep/awake cycle in patients with PD. PMID:25894843

  9. The diagnosis of manganese-induced parkinsonism.

    PubMed

    Cersosimo, Maria G; Koller, William C

    2006-05-01

    Parkinsonism is a clinical syndrome consisting of tremor, bradykinesia, rigidity, gait, balance problems, in addition to various non-motor symptoms. There are many causes of parkinsonism such as neurodegenerative disease, drugs, vascular causes, structural lesions, infections, and toxicants. Parkinson's disease, or idiopathic parkinsonism, is the most common form of parkinsonism observed in the clinic. There is degeneration of the substantia nigra, pars compacta, which results in loss of striatal dopamine. Parkinson's disease is a slowly progressive condition in which there is a dramatic and sustained responsiveness to levodopa therapy. Manganese is an essential trace element that can be associated with neurotoxicity. Hypermanganism can occur in a variety of clinical settings. The clinical symptoms of manganese intoxication include non-specific complaints, neurobehavioral changes, parkinsonism, and dystonia. Although the globus pallidus is the main structure of damage, other basal ganglia areas can also be involved. MRI scans may show globus pallidus changes during (and for a short period after) exposure. Fluorodopa PET scans that assess the integrity of the substantia nigra dopaminergic system are abnormal in Parkinson's disease. However, these scans re-reported to be normal in a few cases studied with manganese-induced parkinsonism. The parkinsonism due to manganese may have some clinical features that occur less commonly in Parkinson's disease, such as kinetic tremor, dystonia, specific gait disturbances, and early mental, balance and speech changes. The clinical signs tend to be bilateral whereas Parkinson's disease begins on one side of the body. Patients with manganese-induced parkinsonism may be younger at the onset of the disease than with Parkinson's disease. Lastly, there appears to be a lack of response to levodopa therapy in manganese-induced parkinsonism. In summary it may be possible to differentiate manganese-induced parkinsonism from Parkinson

  10. Stimulus Timing by People with Parkinson's Disease

    ERIC Educational Resources Information Center

    Wearden, J. H.; Smith-Spark, J. H.; Cousins, Rosanna; Edelstyn, N. M. J.; Cody, F. W. J.; O'Boyle, D. J.

    2008-01-01

    Previous literature suggests that Parkinson's disease is marked by deficits in timed behaviour. However, the majority of studies of central timing mechanisms in patients with Parkinson's disease have used timing tasks with a motor component. Since the motor abnormalities are a defining feature of the condition, the status of timing in Parkinson's…

  11. Hallucinations in Parkinson disease.

    PubMed

    Diederich, Nico J; Fénelon, Gilles; Stebbins, Glenn; Goetz, Christopher G

    2009-06-01

    Patients with Parkinson disease (PD) can experience hallucinations (spontaneous aberrant perceptions) and illusions (misinterpretations of real perceptual stimuli). Of such phenomena, visual hallucinations (VHs) and illusions are the most frequently encountered, although auditory, olfactory and tactile hallucinations can also occur. In cross-sectional studies, VHs occur in approximately one-third of patients, but up to three-quarters of patients might develop VHs during a 20-year period. Hallucinations can have substantial psychosocial effects and, historically, were the main reason for placing patients in nursing homes. Concomitant or overlapping mechanisms are probably active during VHs, and these include the following: central dopaminergic overactivity and an imbalance with cholinergic neurotransmission; dysfunction of the visual pathways, including specific PD-associated retinopathy and functional alterations of the extrastriate visual pathways; alterations of brainstem sleep-wake and dream regulation; and impaired attentional focus. Possible treatments include patient-initiated coping strategies, a reduction of antiparkinson medications, atypical neuroleptics and, potentially, cholinesterase inhibitors. Evidence-based studies, however, only support the use of one atypical neuroleptic, clozapine, and only in patients without dementia. Better phenomenological discrimination, combined with neuroimaging tools, should refine therapeutic options and improve prognosis. The aim of this Review is to present epidemiological, phenomenological, pathophysiological and therapeutic aspects of hallucinations in PD. PMID:19498436

  12. Parkinson disease and exercise.

    PubMed

    Earhart, Gammon M; Falvo, Michael J

    2013-04-01

    Parkinson disease (PD) is a progressive, neurodegenerative movement disorder. PD was originally attributed to neuronal loss within the substantia nigra pars compacta, and a concomitant loss of dopamine. PD is now thought to be a multisystem disorder that involves not only the dopaminergic system, but other neurotransmitter systems whose role may become more prominent as the disease progresses (189). PD is characterized by four cardinal symptoms, resting tremor, rigidity, bradykinesia, and postural instability, all of which are motor. However, PD also may include any combination of a myriad of nonmotor symptoms (195). Both motor and nonmotor symptoms may impact the ability of those with PD to participate in exercise and/or impact the effects of that exercise on those with PD. This article provides a comprehensive overview of PD, its symptoms and progression, and current treatments for PD. Among these treatments, exercise is currently at the forefront. People with PD retain the ability to participate in many forms of exercise and generally respond to exercise interventions similarly to age-matched subjects without PD. As such, exercise is currently an area receiving substantial research attention as investigators seek interventions that may modify the progression of the disease, perhaps through neuroprotective mechanisms. PMID:23720332

  13. Nutraceuticals in Parkinson's Disease.

    PubMed

    Hang, Liting; Basil, Adeline Henry; Lim, Kah-Leong

    2016-09-01

    Current pharmacological strategies for Parkinson's disease (PD), the most common neurological movement disorder worldwide, are predominantly symptom relieving and are often plagued with undesirable side effects after prolonged treatment. Despite this, they remain as the mainstay treatment for PD due to the lack of better alternatives. Nutraceuticals are compounds derived from natural food sources that have certain therapeutic value and the advent of which has opened doors to the use of alternative strategies to tackle neurodegenerative diseases such as PD. Notably, nutraceuticals are able to position themselves as a "safer" strategy due to the fact that they are naturally derived compounds, therefore possibly having less side effects. Significant efforts have been put into better comprehending the role of nutraceuticals in PD, and we will look at some of them in this review. Broadly speaking, these compounds execute their positive effects via modulating signalling pathways, inhibiting oxidative stress, inflammation and apoptosis, as well as regulating mitochondrial homoeostasis. Importantly, we will highlight how a component of green tea, epigallocatechin-3-gallate (EGCG), confers neuroprotection in PD via its ability to activate AMP kinase and articulate how its beneficial effects in PD are possibly due to enhancing mitochondrial quality control. PMID:27147525

  14. Parkinson disease and driving

    PubMed Central

    Classen, Sherrilene; Uc, Ergun Y.

    2012-01-01

    ABSTRACT The growing literature on driving in Parkinson disease (PD) has shown that driving is impaired in PD compared to healthy comparison drivers. PD is a complex neurodegenerative disorder leading to motor, cognitive, and visual impairments, all of which can affect fitness to drive. In this review, we examined studies of driving performance (on-road tests and simulators) in PD for outcome measures and their predictors. We searched through various databases and found 25 (of 99) primary studies, all published in English. Using the American Academy of Neurology criteria, a study class of evidence was assigned (I–IV, I indicating the highest level of evidence) and recommendations were made (Level A: predictive or not; B: probably predictive or not; C: possibly predictive or not; U: no recommendations). From available Class II and III studies, we identified various cognitive, visual, and motor measures that met different levels of evidence (usually Level B or C) with respect to predicting on-road and simulated driving performance. Class I studies reporting Level A recommendations for definitive predictors of driving performance in drivers with PD are needed by policy makers and clinicians to develop evidence-based guidelines. PMID:23150533

  15. Free-water imaging in Parkinson's disease and atypical parkinsonism.

    PubMed

    Planetta, Peggy J; Ofori, Edward; Pasternak, Ofer; Burciu, Roxana G; Shukla, Priyank; DeSimone, Jesse C; Okun, Michael S; McFarland, Nikolaus R; Vaillancourt, David E

    2016-02-01

    Conventional single tensor diffusion analysis models have provided mixed findings in the substantia nigra of Parkinson's disease, but recent work using a bi-tensor analysis model has shown more promising results. Using a bi-tensor model, free-water values were found to be increased in the posterior substantia nigra of Parkinson's disease compared with controls at a single site and in a multi-site cohort. Further, free-water increased longitudinally over 1 year in the posterior substantia nigra of Parkinson's disease. Here, we test the hypothesis that other parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy have elevated free-water in the substantia nigra. Equally important, however, is whether the bi-tensor diffusion model is able to detect alterations in other brain regions beyond the substantia nigra in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy and to accurately distinguish between these diseases. Free-water and free-water-corrected fractional anisotropy maps were compared across 72 individuals in the basal ganglia, midbrain, thalamus, dentate nucleus, cerebellar peduncles, cerebellar vermis and lobules V and VI, and corpus callosum. Compared with controls, free-water was increased in the anterior and posterior substantia nigra of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Despite no other changes in Parkinson's disease, we observed elevated free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of multiple system atrophy, and in all regions examined for progressive supranuclear palsy. Compared with controls, free-water-corrected fractional anisotropy values were increased for multiple system atrophy in the putamen and caudate, and increased for progressive supranuclear palsy in the putamen, caudate, thalamus, and vermis, and decreased in the superior cerebellar peduncle and corpus callosum. For all disease

  16. Parkinsonism in poets and writers.

    PubMed

    Bogousslavsky, Julien; Paciaroni, Maurizio

    2013-01-01

    Parkinson disease is a severe degenerative disease, which is bewildering for its array of clinical features. Writers for the past five centuries have described the associated symptoms. Before the nineteenth century, Miguel de Cervantes wrote Don Quixote de la Mancha and William Shakespeare wrote several tragedies dealing with neurological manifestations that are characteristic of Parkinson disease. From the nineteenth century onward, writers including Charles Dickens, Samuel Beckett, Galway Kinnell, and Harold Pinter among others have showcased in their works classic manifestations of Parkinson disease. This literary attention has led to a greater awareness on the part of the general public regarding this disease and, in turn, has opened the doors to a better understanding of and a better respect for the patients affected by this disease. PMID:24290476

  17. Vaccination strategies for Parkinson disease

    PubMed Central

    Romero-Ramos, Marina; von Euler Chelpin, Marianne; Sanchez-Guajardo, Vanesa

    2014-01-01

    Parkinson disease is the second most common neurodegenerative disease in the world, but there is currently no available cure for it. Current treatments only alleviate some of the symptoms for a few years, but they become ineffective in the long run and do not stop the disease. Therefore it is of outmost importance to develop therapeutic strategies that can prevent, stop, or cure Parkinson disease. A very promising target for these therapies is the peripheral immune system due to its probable involvement in the disease and its potential as a tool to modulate neuroinflammation. But for such strategies to be successful, we need to understand the particular state of the peripheral immune system during Parkinson disease in order to avoid its weaknesses. In this review we examine the available data regarding how dopamine regulates the peripheral immune system and how this regulation is affected in Parkinson disease; the specific cytokine profiles observed during disease progression and the alterations documented to date in patients’ peripheral blood mononuclear cells. We also review the different strategies used in Parkinson disease animal models to modulate the adaptive immune response to salvage dopaminergic neurons from cell death. After analyzing the evidence, we hypothesize the need to prime the immune system to restore natural tolerance against α-synuclein in Parkinson disease, including at the same time B and T cells, so that T cells can reprogram microglia activation to a beneficial pattern and B cell/IgG can help neurons cope with the pathological forms of α-synuclein. PMID:24670306

  18. Parkinson's disease. Diagnosis and treatment.

    PubMed Central

    Ng, D C

    1996-01-01

    Although Parkinson's disease is primarily a neurologic disorder, primary care physicians should be knowledgeable about the disease and its treatment because most patients will see their primary care physician first for their symptoms. Furthermore, in today's setting of managed care, primary care physicians will likely be called on even more to assume primary responsibility for the treatment of patients afflicted with Parkinson's disease; neurologists will likely play the role of consultants who see a patient only periodically and offer recommendations and advice for the primary care physicians to implement. PMID:8987437

  19. Orthostatic Hypotension in Patients with Parkinson's Disease and Atypical Parkinsonism

    PubMed Central

    Lökk, Johan

    2014-01-01

    Orthostatic hypotension (OH) is one of the commonly occurring nonmotor symptoms in patients with idiopathic Parkinson's disease (IPD) and atypical parkinsonism (AP). We aimed to review current evidences on epidemiology, diagnosis, treatment, and prognosis of OH in patients with IPD and AP. Major electronic medical databases were assessed including PubMed/MEDLINE and Embase up to February 2013. English-written original or review articles with keywords such as “Parkinson's disease,” “atypical parkinsonism,” and “orthostatic hypotension” were searched for relevant evidences. We addressed different issues such as OH definition, epidemiologic characteristics, pathophysiology, testing and diagnosis, risk factors for symptomatic OH, OH as an early sign of IPD, prognosis, and treatment options of OH in parkinsonian syndromes. Symptomatic OH is present in up to 30% of IPD, 80% of multiple system atrophy (MSA), and 27% of other AP patients. OH may herald the onset of PD before cardinal motor symptoms and our review emphasises the importance of its timely diagnosis (even as one preclinical marker) and multifactorial treatment, starting with patient education and lifestyle approach. Advancing age, male sex, disease severity, and duration and subtype of motor symptoms are predisposing factors. OH increases the risk of falls, which affects the quality of life in PD patients. PMID:24634790

  20. Imaging prodromal Parkinson disease

    PubMed Central

    Siderowf, Andrew; Stern, Matthew; Seibyl, John; Eberly, Shirley; Oakes, David; Marek, Kenneth

    2014-01-01

    Objectives: The purpose of this study is to evaluate the relative risk of abnormal dopamine transporter (DAT) imaging for subjects with and without hyposmia and the feasibility of acquiring a large, community-based, 2-tiered biomarker assessment strategy to detect prodromal Parkinson disease (PD). Methods: In this observational study, individuals without a diagnosis of PD, recruited through 16 movement disorder clinics, underwent tier 1 assessments (olfactory testing, questionnaires). Tier 2 assessments (neurologic examination, DAT imaging, and other biomarker assessments) were completed by 303 subjects. The main outcome of the study is to compare age-expected [123I]β-CIT striatal binding ratio in hyposmic and normosmic subjects. Results: Tier 1 assessments were mailed to 9,398 eligible subjects and returned by 4,999; 669 were hyposmic. Three hundred three subjects (203 hyposmic, 100 normosmic) completed baseline evaluations. DAT deficit was present in 11% of hyposmic subjects compared with 1% of normosmic subjects. Multiple logistic regression demonstrates hyposmia (odds ratio [OR] 12.4; 95% confidence interval [CI] 1.6, 96.1), male sex (OR 5.5; 95% CI 1.7, 17.2), and constipation (OR 4.3; 95% CI 1.6, 11.6) as factors predictive of DAT deficit. Combining multiple factors (hyposmia, male sex, and constipation) increased the percentage of subjects with a DAT deficit to >40%. Conclusion: Subjects with DAT deficit who do not meet criteria for a diagnosis of PD can be identified by olfactory testing. Sequential biomarker assessment may identify those at risk of PD. Selecting hyposmic individuals enriches the population for DAT deficit, and combining hyposmia with other potential risk factors (male sex, constipation) increases the percentage of subjects with a DAT deficit compatible with prodromal PD. PMID:25298306

  1. Dysphagia in Parkinson's Disease.

    PubMed

    Suttrup, Inga; Warnecke, Tobias

    2016-02-01

    More than 80 % of patients with Parkinson's disease (PD) develop dysphagia during the course of their disease. Swallowing impairment reduces quality of life, complicates medication intake and leads to malnutrition and aspiration pneumonia, which is a major cause of death in PD. Although the underlying pathophysiology is poorly understood, it has been shown that dopaminergic and non-dopaminergic mechanisms are involved in the development of dysphagia in PD. Clinical assessment of dysphagia in PD patients is challenging and often delivers unreliable results. A modified water test assessing maximum swallowing volume is recommended to uncover oropharyngeal dysphagia in PD. PD-specific questionnaires may also be useful to identify patients at risk for swallowing impairment. Fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study are both considered to be the gold standard for evaluation of PD-related dysphagia. In addition, high-resolution manometry may be a helpful tool. These instrumental methods allow a reliable detection of aspiration events. Furthermore, typical patterns of impairment during the oral, pharyngeal and/or esophageal swallowing phase of PD patients can be identified. Therapy of dysphagia in PD consists of pharmacological interventions and swallowing treatment by speech and language therapists (SLTs). Fluctuating dysphagia with deterioration during the off-state should be treated by optimizing dopaminergic medication. The methods used during swallowing treatment by SLTs shall be selected according to the individual dysphagia pattern of each PD patient. A promising novel method is an intensive training of expiratory muscle strength. Deep brain stimulation does not seem to have a clinical relevant effect on swallowing function in PD. The goal of this review is giving an overview on current stages of epidemiology, pathophysiology, diagnosis, and treatment of PD-associated dysphagia, which might be helpful for neurologists

  2. Behavioral dysfunction in Parkinson's disease.

    PubMed

    Friedman, J H

    1998-01-01

    Behavioral manifestations of Parkinson's disease (PD) are often more debilitating than the motor manifestations. These occur both as primary manifestations of the disease and as drug-induced complications. While dementia and abulia are common problems that are not currently treatable, depression and psychosis often respond extremely well to medication. Phenomenology, pathology, and general approaches to treatment will be discussed. PMID:10785833

  3. [The Competence Network Parkinson (CNP)].

    PubMed

    Oertel, Wolfgang H; Deuschl, Guenther; Eggert, Karla

    2016-04-01

    The Competence Network Parkinson (CNP) is a research infrastructure for disease-oriented translational and clinical research in the field of Parkinson syndromes (PS). It was initiated in 1999 and funded until 2008 by the German Ministry for Education and Research (BMBF). The CNP created a highly frequented website with information on PS for the general public and for experts. The CNP designed and established one of the first electronic internet-based data entry systems (secuTrial®) - fulfilling the legal standards of data safety and security - a material bank for genetic research on Parkinson's disease (PD), implemented and investigated new methods for early diagnosis of PD and related atypical PS including in vivo dopamine transporter imaging (DAT SPECT), established the German Parkinson Study Group (GPS-Pharma) with 40 certified trial centres for pharmacotherapeutical trials and the German interdisciplinary Parkinson Study Group (neurology and neurosurgery) for deep brain stimulation (GPS-DBS), and carried out several pharmacoeconomic and health care studies on PD in Germany. Sustainability of the infrastructure CNP has in part been achieved in form of the GPS-Pharma and the GPS-DBS, as well as in the German Study Group on REM Sleep Behaviour Disorder (RBD), a prodromal phase of PD. Part of the CNP activities, such as genetic research and research on cohorts of PD patients, have been incorporated into the German Center for Neurodegenerative Disorders (DZNE). Furthermore, topics such as health care research are funded within projects of the EU research program. The article describes problems in setting up a competence network from scratch and contains recommendations how to avoid them in the future. PMID:26961981

  4. Milestones in Parkinson's disease therapeutics.

    PubMed

    Rascol, Olivier; Lozano, Andres; Stern, Matthew; Poewe, Werner

    2011-05-01

    In the mid-1980s, the treatment of Parkinson's disease was quite exclusively centered on dopatherapy and was focusing on dopamine systems and motor symptoms. A few dopamine agonists and a monoamine oxidase B inhibitor (selegiline) were used as adjuncts in advanced Parkinson's disease. In the early 2010s, levodopa remains the gold standard. New insights into the organization of the basal ganglia paved the way for deep brain stimulation, especially of the subthalamic nucleus, providing spectacular improvement of drug-refractory levodopa-induced motor complications. Novel dopamine agonists (pramipexole, ropinirole, rotigotine), catecholmethyltransferase inhibitors (entacapone), and monoamine oxidase B inhibitors (rasagiline) have also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to improve motor outcomes. Using dopamine agonists early, before levodopa, proved to delay the onset of dyskinesia, although this is achieved at the price of potentially disabling daytime somnolence or impulse control disorders. The demonstration of an antidyskinetic effect of the glutamate antagonist amantadine opened the door for novel nondopaminergic approaches of Parkinson's disease therapy. More recently, nonmotor symptoms (depression, dementia, and psychosis) have been the focus of the first randomized controlled trials in this field. Despite therapeutic advances, Parkinson's disease continues to be a relentlessly progressive disorder leading to severe disability. Neuroprotective interventions able to modify the progression of Parkinson's disease have stood out as a failed therapeutic goal over the last 2 decades, despite potentially encouraging results with compounds like rasagiline. Newer molecular targets, new animal models, novel clinical trial designs, and biomarkers to assess disease modification have created hope for future therapeutic interventions. PMID:21626552

  5. Genetics Home Reference: Wolff-Parkinson-White syndrome

    MedlinePlus

    ... Home Health Conditions Wolff-Parkinson-White syndrome Wolff-Parkinson-White syndrome Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Wolff-Parkinson-White syndrome is a condition characterized by abnormal ...

  6. Adolf Hitler had post-encephalitic Parkinsonism.

    PubMed

    Lieberman, A

    1996-04-01

    Adolf Hitler had Parkinson symptoms in 1934, at age 45 years. He may have had transient symptoms in 1923, at age 34 years. Young-onset parkinsonism, during the 1920s, favored a diagnosis of post-encephalitic rather than idiopathic parkinsonism. Hitler had oculogyric crises, phenomena only associated with post-encephalitic parkinsonism. In addition, he had dystonic facial spasms, palilalia and a sleep disorder, phenomena more likely to be associated with post-encephalitic than idiopathic parkinsonism. In November 1918, at age 29 years, Hitler may have had von Economo's encephalitis, while he was a patient in a hospital, recovering from poison gas. This paper looks at the possible relationship of von Economo's encephalitis to Hitler's asocial behavior; his obsessions and compulsions, his cruelty and rages. The influence of Hitler's parkinsonism on his conduct during World War II is discussed. PMID:18591024

  7. DAT imaging in drug-induced and psychogenic parkinsonism.

    PubMed

    Tolosa, Eduardo; Coelho, Miguel; Gallardo, Marisol

    2003-10-01

    Parkinson's syndrome (PS) is frequently encountered in disorders associated with prominent degeneration of the nigrostriatal pathway as in Parkinson's disease, multisystem atrophy, and progressive supranuclear palsy (presynaptic PS). Drug-induced parkinsonism, a common, underdiagnosed health problem and psychogenic parkinsonism are causes of Parkinson's syndrome which, evidence suggests, occurs without degeneration of nigrostriatal structures. We review clinical features and results of DAT imaging in drug-induced parkinsonism and psychogenic parkinsonism. These two conditions normally give normal striatal DAT imaging results; an abnormal result in either case could exclude both conditions, corroborating a diagnosis of organic parkinsonism in uncertain cases. PMID:14531043

  8. Parkinsonism following dystonia in three patients.

    PubMed

    Katchen, M; Duvoisin, R C

    1986-01-01

    Three patients who presented initially with dystonia and subsequently developed typical idiopathic parkinsonism were evaluated. One patient presented with a writer's cramp, one with axial dystonia, and one with Meige syndrome. All three displayed amelioration of their dystonia with progression of their parkinsonism over a period of 2 to 15 years. Treatment with levodopa gave some relief of the parkinsonism symptoms in two patients but exacerbated or reactivated the dystonia. It is suggested that both the dystonia and the parkinsonism represent the changing clinical expression of the same disorder at different times in its evolution. PMID:3504239

  9. Post-dengue encephalopathy and Parkinsonism.

    PubMed

    Fong, Choong Yi; Hlaing, Chaw Su; Tay, Chee Geap; Ong, Lai Choo

    2014-10-01

    Parkinsonism as a neurologic manifestation of dengue infection is rare with only 1 reported case in an adult patient. We report a case of a 6-year-old child with self-limiting post-dengue encephalopathy and Parkinsonism. This is the first reported pediatric case of post-dengue Parkinsonism and expands the neurologic manifestations associated with dengue infection in children. Clinicians should consider the possibility of post-dengue Parkinsonism in children with a history of pyrexia from endemic areas of dengue. PMID:24776518

  10. Occupational and environmental causes of parkinsonism

    SciTech Connect

    Tanner, C.M. )

    1992-07-01

    Occupational causes of parkinsonism have usually been identified by direct temporal association of an exposure with disease symptoms, although recently a latent period between exposure and disease causation is being investigated. This review presents the definition of parkinsonism as contrasted with Parkinson's disease, notes the general concepts important to the consideration of toxic effects on the central nervous system, and addresses each group of agents known to cause parkinsonism, including common sources of exposure, clinical course, and proposed mechanisms of toxicity. Agents discussed include manganese, carbon disulfide, organic solvents, carbon monoxide, and MTPT and similar agents.58 references.

  11. Familial parkinsonism with depression: a clinicopathological study.

    PubMed

    Bhatia, K P; Daniel, S E; Marsden, C D

    1993-12-01

    A family with autosomal dominant inheritance of an early-onset and rapidly progressive parkinsonian syndrome and associated severe depression is reported. Three members had parkinsonism with depression, 3 had parkinsonism alone, and 2 suffered depression only. Pathological brain examination in 2 members with parkinsonism and depression revealed distinctive changes, with devastation of the substantia nigra, scarce Lewy bodies, and gliosis of the caudate nucleus and globus pallidus. The clinical and pathological findings were similar to those in four previously described families with autosomal dominant parkinsonism, depression, and alveolar hypoventilation. PMID:8250534

  12. Great shakes: famous people with Parkinson disease.

    PubMed

    Jones, Jeffrey M

    2004-12-01

    James Parkinson is credited with the first complete clinical description of the syndrome attributed to his name, Parkinson disease. It is recognized as the first syndrome defined after neurology became a specialty. Descriptions of Parkinson features are rare in antiquity, and famous people with this disorder have not been found before the 1800s. During the 20th century, more and more famous people appear to be afflicted with Parkinson, and this article reviews some of those who have withstood the "test of Time magazine," and examines some of the reasons why the syndrome is a relatively recent disorder. PMID:15646755

  13. Parkinson's disease in the limelight.

    PubMed

    Graul, A I; Kamerkar, S

    2014-09-01

    The 2014 Lasker-DeBakey Clinical Medical Research Award -one of three prestigious awards granted by the Lasker Foundation in recognition of scientists, clinicians and public servants who have made major advances in the understanding, diagnosis, treatment, cure or prevention of human disease- has been granted to two pioneers in the field of Parkinson's disease therapy. In spite of the availability of more than two dozen drugs and fixed-dose combination products to treat the symptoms of Parkinson's disease -most notably the gold standard levodopa, a dopamine precursor- as well as nonpharmacological treatments like deep brain stimulation, many patients do not respond to available drugs or experience breakthrough symptoms, and the disease is ultimately uncurable. This article reviews currently available therapies as well as biomarkers and novel diagnostics. PMID:25313370

  14. Wolff-Parkinson-White syndrome.

    PubMed

    Morscher, J H

    1992-02-01

    Wolff-Parkinson-White (WPW) syndrome is a cardiac conduction disorder that presents with potentially life-threatening consequences. Wolff-Parkinson-White syndrome-induced dysrhythmias account for 20% of all supraventricular tachycardias that occur in the general population. Clinical presentations range from no symptoms to a sudden cardiac arrest. The risk of sudden death is always present with WPW syndrome, and it is the motivating force in the evaluation and treatment of this syndrome. Current diagnostic modalities are accurate in identifying patients with WPW syndrome, but lack the sensitivity to predict sudden cardiac death. This article reviews the history of WPW syndrome, as well as its general characteristics, diagnostic criteria, treatment modalities, and nursing implications. PMID:1554559

  15. Autonomic disorders predicting Parkinson disease

    PubMed Central

    Palma, Jose-Alberto; Kaufmann, Horacio

    2014-01-01

    It is now well recognized that there is a premotor phase of Parkinson disease with hyposmia and REM sleep behavior disorder caused by degeneration of specific CNS neurons. Most patients with PD describe autonomic symptoms at the time of diagnosis suggesting that these features may have potential sensitivity as clinical biomarkers of the premotor phase. The recognition that damage to peripheral autonomic neurons is present in the early stages of Parkinson disease has led to a search for specific abnormalities in autonomic function that could serve as predictive biomarkers. There is evidence that constipation, urinary and sexual dysfunction and more recently decreased cardiac chronotropic response during exercise, are part of the premotor parkinsonian phenotype. The sensitivity and specificity of these features has yet to be accurately assessed. We briefly review the evidence for autonomic dysfunction as biomarkers of premotor PD. PMID:24262198

  16. Exercise therapy for Parkinson's disease.

    PubMed

    Palmer, S S; Mortimer, J A; Webster, D D; Bistevins, R; Dickinson, G L

    1986-10-01

    The outcomes of two different 12-week exercise programs were assessed by machine measurements of motor signs, tests of grip strength, motor coordination and speed, and neurophysiologic determinations of long-latency stretch responses in two groups of Parkinson patients matched for age, sex and stage of disease. The programs tested included an exercise program developed by the United Parkinson Foundation and a program of upper body karate training. Outcomes of these programs were similar. The majority of patients in both groups showed improvements in gait, tremor, grip strength and motor coordination on tasks requiring fine control. In one task involving whole body coordination there was a decline in function, while muscle rigidity was unchanged. The findings suggest that exercise is a useful adjunct to pharmacologic therapy. PMID:3767624

  17. Virtual visits for Parkinson disease

    PubMed Central

    Venkataraman, Vinayak; Donohue, Sean J.; Biglan, Kevin M.; Wicks, Paul

    2014-01-01

    Summary We sought to characterize recommendations and feedback of patients with Parkinson disease, each offered a free telemedicine consultation with a specialist. Visits consisted of history, neurologic examination, and recommendations. Midway through the program, patients were asked to complete an online satisfaction survey. From August 2012 to May 2013, 55 patients in 5 states (mean age 67.8 years) participated, with 80% of visits conducted from their home. Patients with Parkinson disease were recommended to exercise (86%), change current medication (63%), and add new medication (53%). Thirty-three of 35 consecutive patients completed a survey. Patient satisfaction exceeded 90% for virtually all aspects of the visit measured. Providing care to patients in their homes via telemedicine is feasible, results in changes to care, and is well-received. PMID:24790799

  18. Adolf Hitler and His Parkinsonism

    PubMed Central

    Bhattacharyya, Kalyan B.

    2015-01-01

    Research works have suggested almost incontrovertibly, that Adolf Hitler suffered from Parkinsonism. However, the precise nature of his illness had always been controversial and post-encephalitic and idiopathic varieties were the ones which were most commonly thought as the possible etiology. He displayed features like oculogyric crisis, palilalia, and autonomic symptoms which strongly implicate post-encephalitic etiology in the genesis of his illness. Others on the contrary, observed premorbid personality traits like non-flinching mental rigidity, extreme inflexibility, and awesome pedantry; which are often observed in idiopathic Parkinson's disease. Moreover, nonmotor symptoms like disturbed sleep, proneness to temper tantrums, phases of depression, suspiciousness, and lack of trust on colleagues have also been described by various authors. Additionally, he was prescribed methamphetamine by his personal doctor and that might have led to the development of some of the later traits in his personality. PMID:26713007

  19. Adolf Hitler and His Parkinsonism.

    PubMed

    Bhattacharyya, Kalyan B

    2015-01-01

    Research works have suggested almost incontrovertibly, that Adolf Hitler suffered from Parkinsonism. However, the precise nature of his illness had always been controversial and post-encephalitic and idiopathic varieties were the ones which were most commonly thought as the possible etiology. He displayed features like oculogyric crisis, palilalia, and autonomic symptoms which strongly implicate post-encephalitic etiology in the genesis of his illness. Others on the contrary, observed premorbid personality traits like non-flinching mental rigidity, extreme inflexibility, and awesome pedantry; which are often observed in idiopathic Parkinson's disease. Moreover, nonmotor symptoms like disturbed sleep, proneness to temper tantrums, phases of depression, suspiciousness, and lack of trust on colleagues have also been described by various authors. Additionally, he was prescribed methamphetamine by his personal doctor and that might have led to the development of some of the later traits in his personality. PMID:26713007

  20. Cognitive impairment in Parkinson's disease.

    PubMed

    Cosgrove, Jeremy; Alty, Jane Elizabeth; Jamieson, Stuart

    2015-04-01

    Cognitive impairment is a significant non-motor symptom of Parkinson's disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinson's disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinson's disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimer's related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential. PMID:25814509

  1. The Clinical Evaluation of Parkinson's Tremor.

    PubMed

    Zach, Heidemarie; Dirkx, Michiel; Bloem, Bastiaan R; Helmich, Rick C

    2015-01-01

    Parkinson's disease harbours many different tremors that differ in distribution, frequency, and context in which they occur. A good clinical tremor assessment is important for weighing up possible differential diagnoses of Parkinson's disease, but also to measure the severity of the tremor as a basis for further tailored treatment. This can be challenging, because Parkinson's tremor amplitude is typically very variable and context-dependent. Here, we outline how we investigate Parkinson's tremor in the clinic. We describe a simple set of clinical tasks that can be used to constrain tremor variability (cognitive and motor co-activation, several specific limb postures). This may help to adequately characterize the tremor(s) occurring in a patient with Parkinson's disease. PMID:26406126

  2. Asymmetrical Pedaling Patterns in Parkinson's Disease Patients

    PubMed Central

    Penko, Amanda L.; Hirsch, Joshua R.; Voelcker-Rehage, Claudia; Martin, Philip E.; Blackburn, Gordon; Alberts, Jay L.

    2015-01-01

    Background Approximately 1.5 million Americans are affected by Parkinson's disease [1] which includes the symptoms of postural instability and gait dysfunction. Currently, clinical evaluations of postural instability and gait dysfunction consist of a subjective rater assessment of gait patterns using items from the Unified Parkinson's Disease Rating Scale, and assessments can be insensitive to the effectiveness of medical interventions. Current research suggests the importance of cycling for Parkinson's disease patients, and while Parkinson's gait has been evaluated in previous studies, little is known about lower extremity control during cycling. The purpose of this study is to examine the lower extremity coordination patterns of Parkinson's patients during cycling. Methods Twenty five participants, ages 44-72, with a clinical diagnosis of idiopathic Parkinson's disease participated in an exercise test on a cycle ergometer that was equipped with pedal force measurements. Crank torque, crank angle and power produced by right and left leg were measured throughout the test to calculate Symmetry Index at three stages of exercise (20 Watt, 60 Watt, maximum performance). Findings Decreases in Symmetry Index were observed for average power output in Parkinson's patients as workload increased. Maximum power Symmetry Index showed a significant difference in symmetry between performance at both the 20 Watt and 60 Watt stage and the maximal resistance stage. Minimum power Symmetry Index did not show significant differences across the stages of the test. While lower extremity asymmetries were present in Parkinson's patients during pedaling, these asymmetries did not correlate to postural instability and gait dysfunction Unified Parkinson's Disease Rating Scale scores. Interpretation This pedaling analysis allows for a more sensitive measure of lower extremity function than the Unified Parkinson's Disease Rating Scale and may help to provide unique insight into current and

  3. Targeting delivery in Parkinson's disease.

    PubMed

    Newland, Ben; Dunnett, Stephen B; Dowd, Eilís

    2016-08-01

    Disease-modifying therapies for Parkinson's disease (PD), with the potential to halt the neurodegenerative process and to stimulate the protection, repair, and regeneration of dopaminergic neurons, remain a vital but unmet clinical need. Targeting the delivery of current and new therapeutics directly to the diseased brain region (in particular the nigrostriatal pathway) could result in greater improvements in the motor functions that characterise PD. Here, we highlight some of the opportunities and challenges facing the development of the next generation of therapies for patients with PD. PMID:27312875

  4. Atypical parkinsonism: diagnosis and treatment.

    PubMed

    Stamelou, Maria; Bhatia, Kailash P

    2015-02-01

    Atypical parkinsonism comprises typically progressive supranuclear palsy, corticobasal degeneration, and mutilple system atrophy, which are distinct pathologic entities; despite ongoing research, their cause and pathophysiology are still unknown, and there are no biomarkers or effective treatments available. The expanding phenotypic spectrum of these disorders as well as the expanding pathologic spectrum of their classic phenotypes makes the early differential diagnosis challenging for the clinician. Here, clinical features and investigations that may help to diagnose these conditions and the existing limited treatment options are discussed. PMID:25432722

  5. [Music therapy on Parkinson disease].

    PubMed

    Côrte, Beltrina; Lodovici Neto, Pedro

    2009-01-01

    This study is a result of a qualitative research, in the Gerontology and Music therapy scenario. It was analyzed the importance of alternative practices like playing an instrument (piano, violin, etc.), singing, or practicing a guided musical exercise as a therapy activity for elder people with Parkinson Disease. The analysis, systematization and interpretation of the data pointed: music therapy is an excellent way to improve the life of the patient that becomes more sociable, decreasing physical and psychological symptoms ('symptomatology') and the subject change for a singular and own position in the relation with your disease and the people around. PMID:20069199

  6. Normal CAG and CCG repeats in the Huntington`s disease genes of Parkinson`s disease patients

    SciTech Connect

    Rubinsztein, D.C.; Leggo, J.; Barton, D.E.

    1995-04-24

    The clinical features of Parkinson`s disease, particularly rigidity and bradykinesia and occasionally tremor, are seen in juvenile-onset Huntington`s disease. Therefore, the CAG and CCG repeats in the Huntington`s disease gene were investigated in 45 Parkinson`s disease patients and compared to 40 control individuals. All of the Parkinson`s disease chromosomes fell within the normal size ranges. In addition, the distributions of the two repeats in the Parkinson`s disease patients did not differ significantly from those of the control population. Therefore, abnormalities of these trinucleotide repeats in the Huntington`s disease gene are not likely to contribute to the pathogenesis of Parkinson`s disease. 12 refs., 2 figs.

  7. No allelic association between Parkinson`s disease and dopamine D2, D3, and D4 receptor gene polymorphisms

    SciTech Connect

    Nanko, S.; Hattori, M.; Dai, X.Y.

    1994-12-15

    Parkinson`s disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson`s disease. Genetic association studies between Parkinson`s disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson`s disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson`s disease is associated with the dopamine receptor polymorphisms examined. 35 refs., 2 tabs.

  8. Parkinson's disease as a result of aging

    PubMed Central

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-01-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field. PMID:25677794

  9. Interventional trials in atypical parkinsonism.

    PubMed

    Eschlböck, S; Krismer, F; Wenning, G K

    2016-01-01

    Atypical parkinson disorders (APD) are rapidly progressive neurodegenerative diseases with a variable clinical presentation that may even mimic Parkinson's disease. Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are commonly summarized under this umbrella term. Significant developments in research have expanded knowledge and have broadened available symptomatic treatments, particularly for the treatment of neurogenic orthostatic hypotension. Nonetheless, symptomatic support still remains limited in all of these disorders. Currently, there exists no effective treatment to delay disease progression and disease-modifying trials have failed to provide coherent and convincing results. Recent trials of rasagiline (in MSA), rifampicin (in MSA), tideglusib (in PSP) and davunetide (in PSP) reported negative results. Nevertheless, large cohorts of patients were recruited for interventional studies in the last few years which improved our understanding of trial methodology in APDs immensely. In addition, remarkable progress in basic research has been reported recently and will provide a solid foundation for future therapeutic trials. In this review, we will summarize published randomized, placebo-controlled clinical trials (RCTs) in APDs. Additionally, the design of ongoing and unpublished interventions will be presented. PMID:26421389

  10. Parkinsonism Associated with Glucocerebrosidase Mutation

    PubMed Central

    Sunwoo, Mun-Kyung; Kim, Seung-Min; Lee, Sarah

    2011-01-01

    Background Gaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the β-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations. Case Report A 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. 18F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen. Conclusions This case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation. PMID:21779299

  11. Association between Parkinson's Disease and Helicobacter Pylori

    PubMed Central

    Oğuz, Sıdıka

    2016-01-01

    Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258

  12. Association between Parkinson's Disease and Helicobacter Pylori.

    PubMed

    Çamcı, Gülşah; Oğuz, Sıdıka

    2016-04-01

    Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258

  13. Synaptic dysfunction in Parkinson's disease.

    PubMed

    Picconi, Barbara; Piccoli, Giovanni; Calabresi, Paolo

    2012-01-01

    Activity-dependent modifications in synaptic efficacy, such as long-term depression (LTD) and long-term potentiation (LTP), represent key cellular substrates for adaptive motor control and procedural memory. The impairment of these two forms of synaptic plasticity in the nucleus striatum could account for the onset and the progression of motor and cognitive symptoms of Parkinson's disease (PD), characterized by the massive degeneration of dopaminergic neurons. In fact, both LTD and LTP are peculiarly controlled and modulated by dopaminergic transmission coming from nigrostriatal terminals. Changes in corticostriatal and nigrostriatal neuronal excitability may influence profoundly the threshold for the induction of synaptic plasticity, and changes in striatal synaptic transmission efficacy are supposed to play a role in the occurrence of PD symptoms. Understanding of these maladaptive forms of synaptic plasticity has mostly come from the analysis of experimental animal models of PD. A series of cellular and synaptic alterations occur in the striatum of experimental parkinsonism in response to the massive dopaminergic loss. In particular, dysfunctions in trafficking and subunit composition of glutamatergic NMDA receptors on striatal efferent neurons contribute to the clinical features of the experimental parkinsonism. Interestingly, it has become increasingly evident that in striatal spiny neurons, the correct assembly of NMDA receptor complex at the postsynaptic site is a major player in early phases of PD, and it is sensitive to distinct degrees of DA denervation. The molecular defects at the basis of PD progression may be not confined just at the postsynaptic neuron: accumulating evidences have recently shown that the genes linked to PD play a critical role at the presynaptic site. DA release into the synaptic cleft relies on a proper presynaptic vesicular transport; impairment of SV trafficking, modification of DA flow, and altered presynaptic plasticity have

  14. Parkinson's Rates Rising Among American Men

    MedlinePlus

    ... news/fullstory_159464.html Parkinson's Rates Rising Among American Men Smoking is known to help shield against ... from an otherwise very positive health trend among American men over the past few decades: A steep ...

  15. [Problem of alternative medicine in Parkinson's disease].

    PubMed

    Fujimoto, Ken-Ichi

    2013-01-01

    I asked about the usage of alternative medicine to 300 outpatients with Parkinson's disease. 163 patients (54.3%) had experience with health appliance and 128 patients (42.7%) had experience with supplements. There is no health appliance or supplement whose efficacy for Parkinson's disease is approved publicly. Most of the patients understood it but some patients who purchased the goods believed to be effective in Parkinson's disease. In addition some patients feel affected because the purchase price is abnormally high. Continuous usage rate is generally high in supplements, relatively high in massage machine, but significantly low in equipment to move the body, such as muscle training equipment of various types or exercise bike. It seems important to inform this fact to Parkinson's disease patients. PMID:24291878

  16. Gambling, Sex, and…Parkinson's Disease?

    MedlinePlus

    ... are spent, browse our financial information. Learn More Gambling, Sex, and…Parkinson's Disease? By Laura Marsh, M. ... elevated, expansive, grandiose or irritable mood states. Pathological gambling Pathological gambling refers to recurrent, maladaptive gambling behaviors, ...

  17. Parkinson's Rates Rising Among American Men

    MedlinePlus

    ... fullstory_159464.html Parkinson's Rates Rising Among American Men Smoking is known to help shield against the ... disease may be on the rise for U.S. men over the past three decades, and the trend ...

  18. Glycation in Parkinson's disease and Alzheimer's disease.

    PubMed

    Vicente Miranda, Hugo; El-Agnaf, Omar M A; Outeiro, Tiago Fleming

    2016-06-01

    Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society. PMID:26946341

  19. Imaging Systemic Dysfunction in Parkinson's Disease.

    PubMed

    Borghammer, Per; Knudsen, Karoline; Brooks, David J

    2016-06-01

    Parkinson's disease is now widely recognized to be a multisystem disorder affecting the brain and peripheral autonomic nerves. Extensive pathology is present in both the sympathetic and parasympathetic nervous system and the intrinsic gastrointestinal plexuses in patients. Autonomic pathology and symptoms such as constipation can predate the clinical diagnosis by years or decades. Imaging studies have contributed greatly to our understanding of Parkinson's disease but focused primarily on imaging cerebral pathology. However, given the importance of understanding the nature, chronology, and functional consequences of peripheral pathology, there has been renewed interest in imaging peripheral organs in Parkinson's disease. Suitable imaging tools can be divided into two types: radiotracer studies that directly estimate loss of sympathetic or parasympathetic nerve terminals, and imaging modalities to quantitate dysphagia, gastric emptying, esophageal and intestinal transit times, and anorectal dyssynergia. In this review, we summarize current knowledge about peripheral imaging in Parkinson's disease. PMID:27072951

  20. Nutrition and Parkinson's Disease: What Matters Most?

    MedlinePlus

    ... information. Learn More Nutrition and Parkinson's Disease: What Matters Most? Note from PDF: Are you interested in ... calcium-fortified soy-based beverages, orange juice and dark leafy greens), calcium from non-dairy sources may ...

  1. Environmental risk factors for Parkinson's disease and parkinsonism: the Geoparkinson study

    PubMed Central

    Dick, F D; De Palma, G; Ahmadi, A; Scott, N W; Prescott, G J; Bennett, J; Semple, S; Dick, S; Counsell, C; Mozzoni, P; Haites, N; Wettinger, S Bezzina; Mutti, A; Otelea, M; Seaton, A; Söderkvist, P; Felice, A

    2007-01-01

    Objective To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. Methods A case–control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug‐induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer‐administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job‐exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. Results Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure–response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. Conclusions The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk. PMID:17332139

  2. Recent developments in biomarkers in Parkinson disease

    PubMed Central

    Schapira, Anthony H.V.

    2013-01-01

    Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent findings Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. Summary The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more

  3. Michael J. Fox and his Parkinson's disease.

    PubMed

    Kempster, Peter A

    2004-01-01

    Michael J. Fox was a popular and successful film and television comic actor who developed Parkinson's disease at the age of 29 years. His recently published book, Lucky Man, structured around the story of his Parkinson's disease, is an amusing, briskly paced yet introspective memoir that covers the first 40 years of his life. Although quite anecdotal, it contains interesting observations on the preclinical phase of the disorder, evolution of motor fluctuations, and tactics for pharmacological treatment. PMID:14743369

  4. Erectile function and risk of Parkinson's disease.

    PubMed

    Gao, Xiang; Chen, Honglei; Schwarzschild, Michael A; Glasser, Dale B; Logroscino, Giancarlo; Rimm, Eric B; Ascherio, Alberto

    2007-12-15

    Erectile dysfunction is common among individuals with Parkinson's disease, but it is unknown whether it precedes the onset of the classic features of Parkinson's disease. To address this question, the authors examined whether erectile dysfunction was associated with Parkinson's disease risk in the Health Professionals Follow-up Study. Analyses included 32,616 men free of Parkinson's disease at baseline in 1986 who in 2000 completed a retrospective questionnaire with questions on erectile dysfunction in different time periods. Relative risks were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, history of diabetes, and other covariates. Among men who reported their erectile function before 1986, 200 were diagnosed with Parkinson's disease during 1986-2002. Men with erectile dysfunction before 1986 were 3.8 times more likely to develop Parkinson's disease during the follow-up than were those with very good erectile function (relative risk = 3.8, 95% confidence interval: 2.4, 6.0; p < 0.0001). Multivariate-adjusted relative risks of Parkinson's disease were 2.7, 3.7, and 4.0 (95% confidence interval: 1.4, 11.1; p = 0.008) for participants with first onset of erectile dysfunction (before 1986) at 60 or more, 50-59, and less than 50 years of age, respectively, relative to those without erectile dysfunction. In conclusion, in this retrospective analysis in a large cohort of men, the authors observed that erectile dysfunction was associated with a higher risk of developing Parkinson's disease. PMID:17875583

  5. UK Parkinson's Excellence Network: empowering service improvement across the UK.

    PubMed

    Burn, David

    2015-01-01

    Parkinson's UK, together with leading Parkinson's professionals, has set up the UK Parkinson's Excellence Network to bring together the passion and expertise of leading clinicians with the strategic leadership and resources of Parkinson's UK underpinned by the voice of people affected by Parkinson's. Launched in London in February 2015, the Excellence Network aims to drive sustainable improvements in health and social care services. It will provide a more strategic approach to clinical development so that Parkinson's services across health and social care can be transformed to provide the best quality care across the UK. PMID:26107314

  6. [Parkinson's disease and nucleolar stress].

    PubMed

    Zhou, Qingqing; Chen, Yongping; Wei, Qianqian; Shang, Huifang

    2016-06-01

    Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized mainly by motor dysfunction resulting in bradykinesia, rigidity, tremor, gait impairment, and postural instability. The classic pathogenic feature of PD is preferential loss of dopaminergic neurons in the substantia nigra. Downregulation of rRNA transcription is one of major mechanisms to maintain cellular homeostasis under stress conditions. Nucleolar stress has emerged as a component of the degenerative process caused by impaired rRNA transcription and altered nucleolar integrity. Recent study has indicated that the response to stress conditions and quality control mechanisms are impaired in PD, and that metabolic stress may be a trigger mechanism for PD. This review aims to present evidence for a role of nucleolar stress in PD and has summarized mechanisms by which nucleolar stress may play a role in the progression of PD. PMID:27264829

  7. Balance Dysfunction in Parkinson's Disease

    PubMed Central

    Rinalduzzi, Steno; Missori, Paolo; Fattapposta, Francesco; Currà, Antonio

    2015-01-01

    Stability and mobility in functional motor activities depend on a precise regulation of phasic and tonic muscular activity that is carried out automatically, without conscious awareness. The sensorimotor control of posture involves a complex integration of multisensory inputs that results in a final motor adjustment process. All or some of the components of this system may be dysfunctional in Parkinsonian patients, rendering postural instability one of the most disabling features of Parkinson's disease (PD). Balance control is critical for moving safely in and adapting to the environment. PD induces a multilevel impairment of this function, therefore worsening the patients' physical and psychosocial disability. In this review, we describe the complex ways in which PD impairs posture and balance, collecting and reviewing the available experimental evidence. PMID:25654100

  8. Therapeutic directions for Parkinson's disease.

    PubMed

    Shoulson, Ira

    2010-01-01

    The focus on disease-modifying treatments and cures for Parkinson's disease (PD) has raised expectations for quantum leaps and overshadowed incremental gains that have been slowly achieved. Large multi-center clinical trials such as DATATOP and PRECEPT keep on generating new knowledge that is relevant to clinical care as well as experimental therapeutics. The largely unforeseen relationship between circulating uric acid and the occurrence and progression of PD was developed and confirmed in these clinical trials. Systematic follow-up of clinical trial cohorts after conclusion of the interventional phase provides added value that continues to inform about natural history, state and trait biomarkers, and genotype-phenotype relationships. These efforts are enhanced by data mining, public reporting, and timely sharing of data and biological samples. PMID:20187232

  9. Nuclear microscopy in Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Watt, F.; Lee, T.; Thong, P. S. P.; Tang, S. M.

    1995-09-01

    Rats have been subjected to unilateral lesioning with the selective neurotoxin 6-OHDA in order to induce Parkinsonism. Analysis using the NUS Nuclear Microscope facility have shown that iron levels are raised by an average of 26% in the lesioned subtantia nigra region of the brain compared with the non-lesioned side. In addition the background tissue level of iron is also elevated by 31% in the lesioned side, indicating that there is a general increase in iron levels as a result of the lesioning. This result is consistent with the other observations that other diseases of the brain are frequently associated with altered iron levels (eg. progressive nuclear palsy, multiple system atrophy, Alzheimers disease, multiple sclerosis).

  10. [Autonomic features in Parkinson disease].

    PubMed

    Yamamoto, Toshimasa; Tamura, Naotoshi

    2012-04-01

    Nonmotor symptoms such as autonomic and neuropsychiatric dysfunctions, are commonly seen in Parkinson disease (PD). Recent studies have shown that PD is accompanied by cardiac sympathetic denervation and constipation even in the early stage. Neuropathological studies confirmed changes in the cardiac sympathetic nerves and the gastrointestinal tract. These findings suggest that PD neuropathology may occur first in the peripheral autonomic pathways and extend to the central autonomic pathways, in agreement with the "Braak theory". This article will reviews the symptoms and pathophysiology of gastrointestinal dysfunction, urinary disturbance, sexual dysfunction, sweating dysfunction, pupillary autonomic dysfunction, and orthostatic and postprandial hypotension in PD patients, and discuss to organ selectiveness in autonomic dysfunction in PD. PMID:22481512

  11. Parkinson's disease managing reversible neurodegeneration.

    PubMed

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson's disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient's PD symptoms. PMID:27103805

  12. Cholinergic dysfunction in Parkinson's disease.

    PubMed

    Müller, Martijn L T M; Bohnen, Nicolaas I

    2013-09-01

    There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson's disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD. PMID:23943367

  13. Sleep disorders in Parkinson's disease.

    PubMed

    Thorpy, Michael J

    2004-01-01

    Depression, dementia, and physiologic changes contribute to the high prevalence of sleep disturbances in patients with Parkinson's disease (PD). Antiparkinsonian drugs also play a role in insomnia by increasing daytime sleepiness and affecting motor symptoms and depression. Common types of sleep disturbances in PD patients include nocturnal sleep disruption and excessive daytime sleepiness, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, sleep walking and sleep talking, nightmares, sleep terrors, and panic attacks. A thorough assessment should include complete medical and psychiatric histories, sleep history, and a 1- to 2-week sleep diary or Epworth Sleepiness Scale evaluation. Polysomnography or actigraphy may also be indicated. Treatment should address underlying factors such as depression or anxiety. Hypnotic therapy for sleep disturbances in PD patients should be approached with care because of the risks of falling, agitation, drowsiness, and hypotension. Behavioral interventions may also be useful. PMID:15259535

  14. Psychosocial factors in Parkinson's disease.

    PubMed

    MacCarthy, B; Brown, R

    1989-02-01

    Self-report measures were administered to 136 patients with Parkinson's disease in order to explore the relationships between aspects of psychological adjustment (depression, positive affect and acceptance of illness) and physical illness (duration of the illness, stage of illness and functional disability). Many psychosocial variables which, it was hypothesized, might intervene in the relationship between physical and psychological status were also measured. These were coping style, social support, self-esteem, attributions about the onset and course of the illness, perceived control and previous psychiatric history. A variable pattern of relationships between the different indices of psychological adjustment and physical illness emerged. Self-esteem, coping style and practical support contributed significantly to the variance in psychological adjustment. It was concluded that well-being in Parkinsonian patients is not exclusively dependent on a simple relationship between disability and depression, and that other factors should be taken into account in the clinical management of the illness. PMID:2924026

  15. Parkinson's Disease and Systemic Inflammation

    PubMed Central

    Ferrari, Carina C.; Tarelli, Rodolfo

    2011-01-01

    Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the “primed” microglia into an “active” state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease. PMID:21403862

  16. Parkinson's disease and systemic inflammation.

    PubMed

    Ferrari, Carina C; Tarelli, Rodolfo

    2011-01-01

    Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the "primed" microglia into an "active" state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease. PMID:21403862

  17. Genitourinary dysfunction in Parkinson's disease.

    PubMed

    Sakakibara, Ryuji; Uchiyama, Tomoyuki; Yamanishi, Tomonori; Kishi, Masahiko

    2010-01-15

    Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:20077468

  18. Parkinson's disease between internal medicine and neurology.

    PubMed

    Csoti, Ilona; Jost, Wolfgang H; Reichmann, Heinz

    2016-01-01

    General medical problems and complications have a major impact on the quality of life in all stages of Parkinson's disease. To introduce an effective treatment, a comprehensive analysis of the various clinical symptoms must be undertaken. One must distinguish between (1) diseases which arise independently of Parkinson's disease, and (2) diseases which are a direct or indirect consequence of Parkinson's disease. Medical comorbidity may induce additional limitations to physical strength and coping strategies, and may thus restrict the efficacy of the physical therapy which is essential for treating hypokinetic-rigid symptoms. In selecting the appropriate medication for the treatment of any additional medical symptoms, which may arise, its limitations, contraindications and interactions with dopaminergic substances have to be taken into consideration. General medical symptoms and organ manifestations may also arise as a direct consequence of the autonomic dysfunction associated with Parkinson's disease. As the disease progresses, additional non-parkinsonian symptoms can be of concern. Furthermore, the side effects of Parkinson medications may necessitate the involvement of other medical specialists. In this review, we will discuss the various general medical aspects of Parkinson's disease. PMID:26298728

  19. Motivational modes and learning in Parkinson's disease.

    PubMed

    Foerde, Karin; Braun, Erin Kendall; Higgins, E Tory; Shohamy, Daphna

    2015-08-01

    Learning and motivation are intrinsically related, and both have been linked to dopamine. Parkinson's disease results from a progressive loss of dopaminergic inputs to the striatum and leads to impairments in motivation and learning from feedback. However, the link between motivation and learning in Parkinson's disease is not well understood. To address this gap, we leverage a well-established psychological theory of motivation, regulatory mode theory, which distinguishes between two functionally independent motivational concerns in regulating behavior: a concern with having an effect by initiating and maintaining movement (Locomotion) and a concern with establishing what is correct by critically evaluating goal pursuit means and outcomes (Assessment). We examined Locomotion and Assessment in patients with Parkinson's disease and age-matched controls. Parkinson's disease patients demonstrated a selective decrease in Assessment motivation but no change in Locomotion motivation, suggesting that Parkinson's disease leads to a reduced tendency to evaluate and monitor outcomes. Moreover, weaker Assessment motivation was correlated with poorer performance on a feedback-based learning task previously shown to depend on the striatum. Together, these findings link a questionnaire-based personality inventory with performance on a well-characterized experimental task, advancing our understanding of how Parkinson's disease affects motivation with implications for well-being and treatment outcomes. PMID:25552569

  20. Donated Blood Won't Transmit Alzheimer's, Parkinson's Disease

    MedlinePlus

    ... fullstory_159577.html Donated Blood Won't Transmit Alzheimer's, Parkinson's Disease Swedish study of nearly 1.5 ... who have received blood transfusions from patients with Alzheimer's or Parkinson's disease," said Dr. Irving Gomolin, a ...

  1. Thought Processing a Concern of Parkinson's Patients, Study Says

    MedlinePlus

    ... fullstory_157856.html Thought Processing a Concern of Parkinson's Patients, Study Says Those with thinking difficulties struggle ... thinking skills could have a greater impact on Parkinson's disease patients' ability to converse than physical problems, ...

  2. Scientists Zero in On Brain Area Linked to 'Parkinson's Gait'

    MedlinePlus

    ... Scientists Zero in on Brain Area Linked to 'Parkinson's Gait' Discovery could lead to new treatments for ... play a role in walking difficulties that afflict Parkinson's disease patients, new research suggests. The prefrontal cortex ...

  3. [Genetics and present therapy options in Parkinson's disease: a review].

    PubMed

    Bereznai, Benjamin; Molnar, Mária Judit

    2009-05-30

    In the past years, six monogenic forms of Parkinson disease have clearly been associated with this movement disorder. The most frequent forms are LRRK2- and Parkin-associated Parkinson disease. Currently, a genetic diagnosis does not change the therapy, the genes involved in genetic Parkinson disease help to understand the underlying pathophysiologic mechanisms of Parkinson disease. Beside the overview of the molecular-genetic basis, we give a review about genetic testing, pharmacological and other multidisciplinary treatment options. PMID:19579663

  4. Initial treatment of Parkinson's disease.

    PubMed

    Tarsy, Daniel

    2006-05-01

    Initial treatment of early idiopathic Parkinson's disease (PD) begins with diagnosis based on clinical evaluation supplemented by laboratory studies and brain imaging to exclude causes of secondary parkinsonism. In most cases, testing is normal and the diagnosis of PD rests on clinical criteria. In patients with mild symptoms and signs, the diagnosis of PD may not initially be apparent, and follow-up evaluation is needed to arrive at a diagnosis. Once the diagnosis is made, pharmacologic treatment may not be the first step. First, patient education is essential, especially because PD is a high-profile disease for which information and misinformation are readily available to patients and families. Counseling concerning prognosis, future symptoms, future disability, and treatment must be provided. Questions from patients concerning diet, lifestyle, and exercise are especially common at this point. The decision of when to initiate treatment is the next major consideration. Much controversy but relatively little light has been brought to bear on this issue. L-dopa was the first major antiparkinson medication to be introduced and remains the "gold standard" of treatment. Next in efficacy are the dopamine agonists (DAs). A debate has raged concerning whether initial dopaminergic treatment should be with L-dopa or DAs. Physicians have been concerned about forestalling the appearance of dyskinesias and motor fluctuations, whereas patients have incorrectly understood that L-dopa and possibly other antiparkinson drugs have a finite duration of usefulness, making it important to defer treatment for as long as possible. This has created "L-dopa phobia," which may stand in the way of useful treatment. In spite of this controversy, there is uniform agreement that the appropriate time to treat is when the patient is beginning to be disabled. This varies from patient to patient and depends on age, employment status, nature of job, level of physical activity, concern about

  5. Copper and Copper Proteins in Parkinson's Disease

    PubMed Central

    Rivera-Mancia, Susana; Diaz-Ruiz, Araceli; Tristan-Lopez, Luis; Rios, Camilo

    2014-01-01

    Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology. PMID:24672633

  6. [Metronome therapy in patients with Parkinson disease].

    PubMed

    Enzensberger, W; Oberländer, U; Stecker, K

    1997-12-01

    We studied 10 patients with Parkinson's disease and 12 patients with Parkinson-plus-syndrome, trying to improve patients' gait by application of various external rhythmic stimuli, including metronome stimulation (96 beats per minute = middle andante). The test course of the patients was 4 x 10 meters and 3 U-turns. The patients' gait quality under stimulation was compared with their free walk (velocity, number of steps, number of freezing episodes). Metronome stimulation significantly reduced the time and number of steps needed for the test course and also diminished the number of freezing episodes. March music stimulation was less effective and tactile stimulation (rhythmically tapping on the patient's shoulder) even produced negative results. The positive effect of metronome stimulation was also found, when the tests were not performed inside the hospital building, but outside in the hospital parc. Metronome stimulation was comparably effective in both patient sub-groups examined in this study (M. Parkinson, Parkinson-plus-syndrome) and seems to be an important additional help in the treatment of these patients. Electronical metronomes are not expensive, easy in handling, and portable. A theoretical explanation of metronome stimulation effectivity in patients with Parkinson's disease still needs to be elucidated. PMID:9465340

  7. Damage to dopamine systems differs between Parkinson's disease and Alzheimer's disease with parkinsonism.

    PubMed

    Murray, A M; Weihmueller, F B; Marshall, J F; Hurtig, H I; Gottleib, G L; Joyce, J N

    1995-03-01

    Parkinsonism occurs in approximately 35 to 40% of patients with Alzheimer's disease (AD) even with little or no neuronal degeneration in the substantia nigra, which in idiopathic Parkinson's disease (PD) results in the severe loss of striatal dopamine transporter sites. It is not known if there is a loss of striatal dopamine transporter sites in AD with coexistent parkinsonism (AD/parkinsonism). We quantified the pattern of these sites in the striatum and midbrain of patients with the clinical diagnosis of PD, AD, and AD/parkinsonism in comparison with a group of age-matched control subjects. We also quantified the number of D2 receptors and the levels of tyrosine hydroxylase in the substantia nigra and ventral tegmental area of the same groups. The results showed that in AD the loss of dopamine transporter sites was restricted to the nucleus accumbens. The loss of these sites in the AD/parkinsonism group was more extensive than in the AD group, with the most severe losses in the rostral caudate and putamen and least in the caudal caudate and putamen. While the PD group showed an equally severe reduction in numbers of sites, the caudal to rostral gradient of loss differed from that in the AD/parkinsonism group. The PD group also showed a marked loss of dopamine transporter sites, tyrosine hydroxylase, and D2 autoreceptors (located on dopamine neurons) in the substantia nigra and ventral tegmental area. In contrast, no reductions in dopamine transporter sites, tyrosine hydroxylase, and D2 autoreceptors were observed in the substantia nigra and ventral tegmental area of the AD or AD/parkinsonism groups. Thus, the loss of striatal dopamine transporter sites in AD/parkinsonism may be related to the clinical parkinsonian symptoms. However, the loss is not simply the result of neuronal degeneration in the substantia nigra, but must derive from other processes. PMID:7695230

  8. Early diagnosis of Parkinson's disease.

    PubMed

    Becker, Georg; Müller, Antje; Braune, Stefan; Büttner, Thomas; Benecke, Reiner; Greulich, Wolfgang; Klein, Wolfgang; Mark, Günter; Rieke, Jürgen; Thümler, Reiner

    2002-10-01

    In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an 'advanced stage' of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection. The discovery of several genetic mutations associated with IPD raises the possibility that these, or other biomarkers, of the disease may help to identify persons at risk of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related to an increased iron load of the substantia nigra. In the early clinical phase, a number of motor and particularly non-motor signs emerge, which can be identified by the patients and physicians years before the diagnosis is made, notably olfactory dysfunction, depression, or 'soft' motor signs such as changes in handwriting, speech or reduced ambulatory arm motion. These signs of the early, prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer tests. As one single instrument will not be sensitive enough, a battery of tests has to be composed measuring independent parameters of the incipient disease. Subjects with abnormal findings in this test battery should than be submitted to nuclear medicine examinations to quantify the extent of dopaminergic injury and to reach the goal of a reliable, early diagnosis. PMID:12522572

  9. Genetic comorbidities in Parkinson's disease

    PubMed Central

    Nalls, Mike A.; Saad, Mohamad; Noyce, Alastair J.; Keller, Margaux F.; Schrag, Anette; Bestwick, Jonathan P.; Traynor, Bryan J.; Gibbs, J. Raphael; Hernandez, Dena G.; Cookson, Mark R.; Morris, Huw R.; Williams, Nigel; Gasser, Thomas; Heutink, Peter; Wood, Nick; Hardy, John; Martinez, Maria; Singleton, Andrew B.

    2014-01-01

    Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain. PMID:24057672

  10. Gut dysfunction in Parkinson's disease.

    PubMed

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-07-01

    Early involvement of gut is observed in Parkinson's disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  11. Environmental Exposures and Parkinson's Disease.

    PubMed

    Nandipati, Sirisha; Litvan, Irene

    2016-01-01

    Parkinson's disease (PD) affects millions around the world. The Braak hypothesis proposes that in PD a pathologic agent may penetrate the nervous system via the olfactory bulb, gut, or both and spreads throughout the nervous system. The agent is unknown, but several environmental exposures have been associated with PD. Here, we summarize and examine the evidence for such environmental exposures. We completed a comprehensive review of human epidemiologic studies of pesticides, selected industrial compounds, and metals and their association with PD in PubMed and Google Scholar until April 2016. Most studies show that rotenone and paraquat are linked to increased PD risk and PD-like neuropathology. Organochlorines have also been linked to PD in human and laboratory studies. Organophosphates and pyrethroids have limited but suggestive human and animal data linked to PD. Iron has been found to be elevated in PD brain tissue but the pathophysiological link is unclear. PD due to manganese has not been demonstrated, though a parkinsonian syndrome associated with manganese is well-documented. Overall, the evidence linking paraquat, rotenone, and organochlorines with PD appears strong; however, organophosphates, pyrethroids, and polychlorinated biphenyls require further study. The studies related to metals do not support an association with PD. PMID:27598189

  12. [Cognitive dysfunction in Parkinson's disease].

    PubMed

    Maruyama, T

    2000-10-01

    The neuropsychological impairments associated with Parkinson's disease(PD) have been often documented. However, the pathological mechanisms underlying cognitive dysfunction are hardly solved, as compared with motor dysfunction. Moreover, the precise relationships between the two dysfunctions have remained aloof. This paper attempts to clarify three specific domains of isolated cognitive impairments: dysexecutive syndrome, memory disturbance, and bradyphrenia, which are specifically observed in PD. It especially discusses the neuropsychological relationships between these impairments and the stages of illness. Several neuropsychological experiments to examine these three domains of cognitive impairments were conducted. Significant results were obtained in the following: set-shifting and divergent thinking were significantly impaired in both the early group and the advanced group; while set-maintaining, procedural learning, and cognitive speed, were only significantly disturbed in the advanced group. The failure to acquire procedural skills and the slowing of cognitive speed, were correlated with decreased attention of working memory in the advanced group. These results indicate that the shifting of cognitive sets maybe disturbed in the embryonic stage of the disease. The results also indicated that other cognitive dysfunctions might manifest themselves during the advanced stages due to attentional deficits. In conclusion, it is possible that other neurotransmitters maybe involved in the progressive degeneration of other systems in addition to the dopaminergic system. For example: serotoninergic, noradrenergic and cholinergic systems. Therefore, further research is required to establish which neurotransmitters are involved in their corresponding cognitive impairments in PD. PMID:11068439

  13. [Molecular genetics of Parkinson's disease].

    PubMed

    Toda, Tatsushi

    2007-08-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder in the world. The occurrence of PD is largely sporadic, while several families with Mendelian segregation of PD have been reported. PD is thought to be caused by mitochondrial dysfunction, oxidative stress and inflammation based on multiple genetic and environmental factors, resulting in the apoptosis of dopaminergic cells. Six causal genes for Mendelian inherited PD have been identified to date, which indicate the importance of the ubiquitin-proteasome pathway in the molecular pathogenesis of dopaminergic cell death. Recent studies have also indicated the involvement of genetic factors in the pathogenesis of sporadic PD. Many association studies on candidate genes have examined the relationship between PD and polymorphisms; We identified a-synuclein as a definite susceptibility gene for sporadic PD. Since 2001, significant linkage to several loci have been reported in samples of affected sibling pairs. With the recent advances in human genome analyses, genome-wide association studies by SNP chip are being performed to identify susceptibility genes and to establish tailor-made medicine for PD. PMID:17713117

  14. Genetic comorbidities in Parkinson's disease.

    PubMed

    Nalls, Mike A; Saad, Mohamad; Noyce, Alastair J; Keller, Margaux F; Schrag, Anette; Bestwick, Jonathan P; Traynor, Bryan J; Gibbs, J Raphael; Hernandez, Dena G; Cookson, Mark R; Morris, Huw R; Williams, Nigel; Gasser, Thomas; Heutink, Peter; Wood, Nick; Hardy, John; Martinez, Maria; Singleton, Andrew B

    2014-02-01

    Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain. PMID:24057672

  15. Nonmotor manifestations of Parkinson's disease.

    PubMed

    Simuni, Tanya; Sethi, Kapil

    2008-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Traditionally, attention has focused on the motor symptomatology of PD, but it is now appreciated that the nonmotor symptoms affecting neuropsychiatric, sleep, autonomic, and sensory domains occur in up to 88% of PD patients and can be an important source of disability. Nonmotor manifestations of PD play a significant role in the impairment of disease-related quality of life. The cause of nonmotor manifestations of PD is multifactorial, but to a large extent, these manifestations are related to the nature of the neurodegenerative process and the widespread nondopaminergic neuropathological changes associated with the disease. Recognition of nonmotor disability is essential not only for ascertaining the functional status of patients but also for better appreciating the nature of the neurodegenerative process in PD. In addition, a number of nonmotor manifestations can precede the onset of motor symptoms in PD and can be used as screening tools allowing for early disease identification and for trials of possible disease-modifying interventions. This article reviews depression, sleep, and autonomic dysfunction in PD. PMID:19127582

  16. Gene therapy for Parkinson's disease.

    PubMed

    Lawlor, Patricia A; During, Matthew J

    2004-03-01

    Parkinson's disease (PD) is a debilitating neurodegenerative disorder arising from loss of dopaminergic neurons in the substantia nigra pars compacta and subsequent depletion of striatal dopamine levels, which results in distressing motor symptoms. The current standard pharmacological treatment for PD is direct replacement of dopamine by treatment with its precursor, levodopa (L-dopa). However, this does not significantly alter disease progression and might contribute to the ongoing pathology. Several features of PD make this disease one of the most promising targets for clinical gene therapy of any neurological disease. The confinement of the major pathology to a compact, localised neuronal population and the anatomy of the basal ganglia circuitry mean that global gene transfer is not required and there are well-defined sites for gene transfer. The multifactorial aetiology of idiopathic PD means that it is unlikely any single gene will cure the disease, and as a result at least three separate gene-transfer strategies are currently being pursued: transfer of genes for enzymes involved in dopamine production; transfer of genes for growth factors involved in dopaminergic cell survival and regeneration; and transfer of genes to reset neuronal circuitry by switching cellular phenotype. The merits of these strategies are discussed here, along with remaining hurdles that might impede transfer of gene therapy technology to the clinic as a treatment for PD. PMID:15000692

  17. Safinamide for symptoms of Parkinson's disease.

    PubMed

    Müller, T

    2015-11-01

    Chronic and slow progression of neuronal death in Parkinson's disease is responsible for an altered neurotransmission of various biogenic amines, such as dopamine. Therefore, an individually different pronounced heterogeneity of motor and nonmotor symptoms characterizes each Parkinson's disease patient. Ideal candidates for the balance of these neurotransmitter deficits are compounds like safinamide with broad mechanisms of action such as reversible monoamine oxidase type B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and of glutamate release. Safinamide is administered one time daily with oral doses ranging from 50 to 100 mg. Safinamide was well tolerated and safe, ameliorated motor symptoms when combined with dopamine agonist only or additional levodopa in clinical trials. Safinamide is a novel instrument for the drug therapy of Parkinson's disease with better safety and tolerability particularly concerning diarrhea than inhibitors of catechol-O-methyltransferase, like entacapone, according to an indirect comparison within a meta-analysis with entacapone. PMID:26744740

  18. Parkinsonism and frontotemporal dementia: the clinical overlap.

    PubMed

    Espay, Alberto J; Litvan, Irene

    2011-11-01

    Frontotemporal dementia is commonly associated with parkinsonism in several sporadic (i.e., progressive supranuclear palsy, corticobasal degeneration) and familial neurodegenerative disorders (i.e., frontotemporal dementia associated with parkinsonism and MAPT or progranulin mutations in chromosome 17). The clinical diagnosis of these disorders may be challenging in view of overlapping clinical features, particularly in speech, language, and behavior. The motor and cognitive phenotypes can be viewed within a spectrum of clinical, pathologic, and genetic disorders with no discrete clinicopathologic correlations but rather lying within a dementia-parkinsonism continuum. Neuroimaging and cerebrospinal fluid analysis can be helpful, but the poor specificity of clinical and imaging features has enormously challenged the development of biological markers that could differentiate these disorders premortem. This gap is critical to bridge in order to allow testing of novel biological therapies that may slow the progression of these proteinopathies. PMID:21892619

  19. Cognitive dysfunction in early onset parkinsonism.

    PubMed

    Tsai, C H; Lu, C S; Hua, M S; Lo, W L; Lo, S K

    1994-01-01

    Cognitive functions of 24 patients with early onset parkinsonism (age of onset before 40 years) and 24 controls were investigated by a battery of neuropsychological tests. Patients were shown to be impaired in performance IQ (PIQ), conceptual ability and regulation behavior, memory, visuospatial perception, and manual dexterity. Patients were also shown to have a higher Zung Depression score. However, analysis of the testing scores appeared to indicate that only a small portion of poor performance on neuropsychological tests are depression related. The results demonstrated that patients with early onset parkinsonism, in whom the factor of aging is not as important, still show cognitive dysfunction and suggested that Parkinson's disease itself can cause cognitive impairment. PMID:8178636

  20. Drugs of abuse and Parkinson's disease.

    PubMed

    Mursaleen, Leah R; Stamford, Jonathan A

    2016-01-01

    The term "drug of abuse" is highly contextual. What constitutes a drug of abuse for one population of patients does not for another. It is therefore important to examine the needs of the patient population to properly assess the status of drugs of abuse. The focus of this article is on the bidirectional relationship between patients and drug abuse. In this paper we will introduce the dopaminergic systems of the brain in Parkinson's and the influence of antiparkinsonian drugs upon them before discussing this synergy of condition and medication as fertile ground for drug abuse. We will then examine the relationship between drugs of abuse and Parkinson's, both beneficial and deleterious. In summary we will draw the different strands together and speculate on the future merit of current drugs of abuse as treatments for Parkinson's disease. PMID:25816790

  1. Grammatical abilities in Parkinson's disease: evidence from written sentences.

    PubMed

    Small, J A; Lyons, K; Kemper, S

    1997-12-01

    This study examined the grammatical content of written sentences elicited from 96 Parkinson's patients, 30 Parkinson's with dementia patients and 167 control subjects. Parkinson's patients without dementia or with mild dementia presented no impairments in sentence length, syntactic complexity or amount of information content. Moderately demented Parkinson's patients showed reduced sentence length and information content but normal syntactic complexity. This pattern of results provides evidence that lexical-semantic content is more susceptible to decline than syntactic structure with the progression of dementia in Parkinson's disease. PMID:9460727

  2. Multiple Modes of Impulsivity in Parkinson's Disease

    PubMed Central

    Nombela, Cristina; Rittman, Timothy; Robbins, Trevor W.; Rowe, James B.

    2014-01-01

    Cognitive problems are a major factor determining quality of life of patients with Parkinson's disease. These include deficits in inhibitory control, ranging from subclinical alterations in decision-making to severe impulse control disorders. Based on preclinical studies, we proposed that Parkinson's disease does not cause a unified disorder of inhibitory control, but rather a set of impulsivity factors with distinct psychological profiles, anatomy and pharmacology. We assessed a broad set of measures of the cognitive, behavioural and temperamental/trait aspects of impulsivity. Sixty adults, including 30 idiopathic Parkinson's disease patients (Hoehn and Yahr stage I–III) and 30 healthy controls, completed a neuropsychological battery, objective behavioural measures and self-report questionnaires. Univariate analyses of variance confirmed group differences in nine out of eleven metrics. We then used factor analysis (principal components method) to identify the structure of impulsivity in Parkinson's disease. Four principal factors were identified, consistent with four different mechanisms of impulsivity, explaining 60% of variance. The factors were related to (1) tests of response conflict, interference and self assessment of impulsive behaviours on the Barrett Impulsivity Scale, (2) tests of motor inhibitory control, and the self-report behavioural approach system, (3) time estimation and delay aversion, and (4) reflection in hypothetical scenarios including temporal discounting. The different test profiles of these four factors were consistent with human and comparative studies of the pharmacology and functional anatomy of impulsivity. Relationships between each factor and clinical and demographic features were examined by regression against factor loadings. Levodopa dose equivalent was associated only with factors (2) and (3). The results confirm that impulsivity is common in Parkinson's disease, even in the absence of impulse control disorders, and that it is

  3. Myopathy and parkinsonism in phosphoglycerate kinase deficiency.

    PubMed

    Sotiriou, Evangelia; Greene, Paul; Krishna, Sindu; Hirano, Michio; DiMauro, Salvatore

    2010-05-01

    A 25-year-old man with exertional myoglobinuria had no evidence of hemolytic anemia, but he had severe parkinsonism that was responsive to levodopa. Phosphoglycerate kinase (PGK) activity was markedly decreased in muscle, and molecular analysis of the PGK1 gene identified the p.T378P mutation that was recently reported in a patient with isolated myopathy. This case reinforces the concept that PGK deficiency is a clinically heterogeneous disorder and raises the question of a relationship between PGK deficiency and idiopathic juvenile Parkinson disease. PMID:20151463

  4. Parkinson's disease: initial treatment of motor disorders.

    PubMed

    2015-09-01

    Parkinson's disease is characterised by three main symptoms: slowness and paucity of movements, rigidity, and resting tremor. Rapid improvement in these symptoms after levodopa administration supports the diagnosis of Parkinson's disease. It is important to inform the patient tactfully, allowing him or her to control the pace at which information on the diagnosis, symptoms and prognosis is conveyed. Patients with minimal discomfort or mild disability derive little benefit from drug therapy. Physiotherapy and physical exercises are sometimes useful. Previously untreated patients with marked functional impairment should receive medication. The choice is essentially between levodopa and ropinirole, and mainly depends on the patient's age. PMID:26417634

  5. [Impulse control disorders in Parkinson's disease].

    PubMed

    Joutsa, Juho; Kaasinen, Valtteri

    2013-01-01

    Of the patients having Parkinson's disease, up to third encounters some degree of impulse control problems and one out of seven suffers from true impulse control disorders such as pathological gambling, hypersexuality, compulsive shopping and binge eating. Dopaminergic drugs used in anti-Parkinson therapy, especially dopamine agonists, increase the risk of these disorders. Impulse control disorders are associated with a relatively more active dopamine-mediated neurotransmission of the mesolimbic and mesocortical system. Discontinuation of dopamine agonist medication can thus be considered as the first line treatment of these disorders. PMID:24397147

  6. Idiopathic Parkinson's disease: epidemiology, diagnosis and management.

    PubMed Central

    Ben-Shlomo, Y; Sieradzan, K

    1995-01-01

    Since the introduction of levodopa therapy for idiopathic Parkinson's disease over 20 years ago, there has been an awakening of research interest in this chronic neuro-degenerative disorder. This paper describes current understanding of the role of genetic and environmental factors in the aetiology of idiopathic Parkinson's disease and problems associated with both diagnosis and management. It briefly outlines both pharmacological and non-pharmacological options for treatment. Despite an increasing armoury of available treatments, the optimum management for this condition remains controversial. PMID:7619574

  7. A Case of SSRI Induced Irreversible Parkinsonism

    PubMed Central

    Khan, Shahbaj A; Azad, Sudip

    2015-01-01

    Serotonin specific reuptake inhibitors (SSRI) are widely used antidepressants for variety of clinical conditions and have found popularity. They are sometimes associated with extrapyramidal side effects including Parkinsonism. We report a case of generalized anxiety disorder on treatment with SSRI (fluoxetine / sertraline) who developed irreversible Parkinsonism. SSRI are known to cause reversible or irreversible motor disturbances through pathophysiological changes in basal ganglion motor system by altering the dopamine receptors postsynaptically. Clinician should keep risk benefit ratio in mind and change of antidepressant of different class may be considered. Case is reported to alert physicians to possibility of motor system damage while treating with SSRI. PMID:25859504

  8. Oxidative Stress in Genetic Mouse Models of Parkinson's Disease

    PubMed Central

    Varçin, Mustafa; Bentea, Eduard; Michotte, Yvette; Sarre, Sophie

    2012-01-01

    There is extensive evidence in Parkinson's disease of a link between oxidative stress and some of the monogenically inherited Parkinson's disease-associated genes. This paper focuses on the importance of this link and potential impact on neuronal function. Basic mechanisms of oxidative stress, the cellular antioxidant machinery, and the main sources of cellular oxidative stress are reviewed. Moreover, attention is given to the complex interaction between oxidative stress and other prominent pathogenic pathways in Parkinson's disease, such as mitochondrial dysfunction and neuroinflammation. Furthermore, an overview of the existing genetic mouse models of Parkinson's disease is given and the evidence of oxidative stress in these models highlighted. Taken into consideration the importance of ageing and environmental factors as a risk for developing Parkinson's disease, gene-environment interactions in genetically engineered mouse models of Parkinson's disease are also discussed, highlighting the role of oxidative damage in the interplay between genetic makeup, environmental stress, and ageing in Parkinson's disease. PMID:22829959

  9. Transcranial sonography findings in welding-related Parkinsonism in comparison to Parkinson's disease.

    PubMed

    Walter, Uwe; Dressler, Dirk; Lindemann, Christian; Slachevsky, Andrea; Miranda, Marcelo

    2008-01-01

    The pathogenetic relationship of welding-related Parkinsonism (WP) and idiopathic Parkinson's disease (PD) is a matter of debate. In the present study, we compared transcranial sonography (TCS) findings in patients with WP and PD. Two male patients with WP, who had developed levodopa-resistant akinetic-rigid Parkinsonism without ongoing progression after having worked as welders for many years in Chilean mines in confined spaces without adequate ventilation, and three age-matched male patients with clinically definite akinetic-rigid PD were studied with TCS in a random order by two investigators blind to clinical diagnoses. In both WP patients, normal echogenicity of substantia nigra was found whereas all PD patients exhibited marked substantia nigra hyperechogenicity, previously reported as a characteristic TCS finding in idiopathic PD. In contrast, lenticular nucleus was hyperechogenic in both WP patients but only in one of the PD patients. TCS findings suggest a different pathophysiology of Parkinsonism in WP and PD patients. PMID:17987651

  10. Parkinsonism in FMR1 premutation carriers may be indistinguishable from Parkinson disease

    PubMed Central

    Hall, Deborah A.; Howard, Katherine; Hagerman, Randi; Leehey, Maureen A.

    2009-01-01

    Premutation carriers of repeat expansions in the fragile X mental retardation (FMR1) gene develop kinetic tremor and ataxia or the ‘fragile X associated tremor/ataxia syndrome’ (FXTAS). Affected FMR1 premutation carriers also have parkinsonism, but have not been reported to meet criteria for Parkinson disease. This case series illustrates that some patients who are FMR1 premutation carriers may appear by history and examination to have idiopathic Parkinson disease. Based on previous studies, it is likely that the genetic mutation and parkinsonism are associated. Although screening all PD patients is likely to be low yield, genetic testing of FMR1 in individuals with PD and a family history of fragile X syndrome, autism or developmental delay, or other related FMR1 phenotypes is warranted. PMID:18565783

  11. Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and Distinguishable Features.

    PubMed

    Kwakye, Gunnar F; Paoliello, Monica M B; Mukhopadhyay, Somshuvra; Bowman, Aaron B; Aschner, Michael

    2015-07-01

    Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson's disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson's disease (PD). PMID:26154659

  12. Cell therapy in Parkinson's disease.

    PubMed

    Lindvall, Olle; Björklund, Anders

    2004-10-01

    The clinical studies with intrastriatal transplants of fetal mesencephalic tissue in Parkinson's disease (PD) patients have provided proof-of-principle for the cell replacement strategy in this disorder. The grafted dopaminergic neurons can reinnervate the denervated striatum, restore regulated dopamine (DA) release and movement-related frontal cortical activation, and give rise to significant symptomatic relief. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. However, there are currently several problems linked to the use of fetal tissue: 1) lack of sufficient amounts of tissue for transplantation in a large number of patients, 2) variability of functional outcome with some patients showing major improvement and others modest if any clinical benefit, and 3) occurrence of troublesome dyskinesias in a significant proportion of patients after transplantation. Thus, neural transplantation is still at an experimental stage in PD. For the development of a clinically useful cell therapy, we need to define better criteria for patient selection and how graft placement should be optimized in each patient. We also need to explore in more detail the importance for functional outcome of the dissection and cellular composition of the graft tissue as well as of immunological mechanisms. Strategies to prevent the development of dyskinesias after grafting have to be developed. Finally, we need to generate large numbers of viable DA neurons in preparations that are standardized and quality controlled. The stem cell technology may provide a virtually unlimited source of DA neurons, but several scientific issues need to be addressed before stem cell-based therapies can be tested in PD patients. PMID:15717042

  13. Psychiatric aspects of Parkinson's disease

    PubMed Central

    Grover, Sandeep; Somaiya, Mansi; Kumar, Santhosh; Avasthi, Ajit

    2015-01-01

    Parkinson's disease (PD) is essentially characterized by the motor symptoms in the form of resting tremor, rigidity and bradykinesia. However, over the years it has been recognized that motor symptoms are just the “tip of the iceberg” of clinical manifestations of PD. Besides motor symptoms, PD characterized by many non-motor symptoms, which include cognitive decline, psychiatric disturbances (depression, psychosis and impulse control), sleep difficulties, autonomic failures (gastrointestinal, cardiovascular, urinary, thermoregulation) and pain syndrome. This review evaluates the various aspects of psychiatric disorders including cognitive decline and sleep disturbances in patients with PD. The prevalence rate of various psychiatric disorders is high in patients with PD. In terms of risk factors, various demographic, clinical and treatment-related variables have been shown to be associated with higher risk of development of psychiatric morbidity. Evidence also suggests that the presence of psychiatric morbidity is associated with poorer outcome. Randomized controlled trials, evaluating the various pharmacological and non-pharmacological treatments for management of psychiatric morbidity in patients with PD are meager. Available evidence suggests that tricyclic antidepressants like desipramine and nortriptyline are efficacious for management of depression. Among the antipsychotics, clozapine is considered to be the best choice for management of psychosis in patients with PD. Among the various cognitive enhancers, evidence suggest efficacy of rivastigmine in management of dementia in patients with PD. To conclude, this review suggests that psychiatric morbidity is highly prevalent in patients with PD. Hence, a multidisciplinary approach must be followed to improve the overall outcome of PD. Further studies are required to evaluate the efficacy of various other measures for management of psychiatric morbidity in patients with PD. PMID:25552854

  14. Parkinson disease and smoking revisited

    PubMed Central

    Lee, Pei-Chen; Lassen, Christina F.; Arah, Onyebuchi A.

    2014-01-01

    Objective: To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being “neuroprotective,” we analyzed information about ease of quitting and nicotine substitute use. Methods: For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders. Results: Fewer patients with PD than controls ever established a smoking habit. Among former smokers, those with greater difficulty quitting or using nicotine substitutes were less likely to develop PD, with the risk being lowest among those reporting “extremely difficult to quit” compared with “easy to quit.” Nicotine substitute usage was strongly associated with quitting difficulty and duration of smoking, i.e., most strongly among current smokers, followed by former smokers who had used nicotine substitutes, and less strongly among former smokers who never used substitutes. Conclusions: Our data support the notion that patients with PD are able to quit smoking more easily than controls. These findings are compatible with a decreased responsiveness to nicotine during the prodromal phase of PD. We propose that ease of smoking cessation is an aspect of premanifest PD similar to olfactory dysfunction, REM sleep disorders, or constipation and suggests that the apparent “neuroprotective” effect of smoking observed in epidemiologic studies is due to reverse causation. PMID:25217056

  15. Synaptic dysfunction in Parkinson's disease.

    PubMed

    Bagetta, Vincenza; Ghiglieri, Veronica; Sgobio, Carmelo; Calabresi, Paolo; Picconi, Barbara

    2010-04-01

    In neuronal circuits, memory storage depends on activity-dependent modifications in synaptic efficacy, such as LTD (long-term depression) and LTP (long-term potentiation), the two main forms of synaptic plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder characterized by the massive degeneration of dopaminergic neurons projecting to the striatum. In fact, a peculiar aspect of striatal plasticity is the modulation exerted by DA (dopamine) on LTP and LTD. Our understanding of these maladaptive forms of plasticity has mostly come from the electrophysiological, molecular and behavioural analyses of experimental animal models of PD. In PD, a host of cellular and synaptic changes occur in the striatum in response to the massive loss of DA innervation. Chronic L-dopa therapy restores physiological synaptic plasticity and behaviour in treated PD animals, but most of them, similarly to patients, exhibit a reduction in the efficacy of the drug and disabling AIMs (abnormal involuntary movements) defined, as a whole, as L-dopa-induced dyskinesia. In those animals experiencing AIMs, synaptic plasticity is altered and is paralleled by modifications in the postsynaptic compartment. In particular, dysfunctions in trafficking and subunit composition of NMDARs [NMDA (N-methyl-D-aspartate) receptors] on striatal efferent neurons result from chronic non-physiological dopaminergic stimulation and contribute to the pathogenesis of dyskinesias. According to these pathophysiological concepts, therapeutic strategies targeting signalling proteins coupled to NMDARs within striatal spiny neurons could represent new pharmaceutical interventions for PD and L-dopa-induced dyskinesia. PMID:20298209

  16. Nutritional therapies in Parkinson's disease.

    PubMed

    Evatt, Marian L

    2007-05-01

    Advise patients with Parkinson's disease (PD) to consume a balanced diet, with special attention to adequate intake of dietary fiber, fluids, and macro- and micronutrients. Regularly reassess patients' nutritional history and anthropomorphic measures (height and weight), particularly in patients with advanced disease. PD-related psychosocial as well as physical and cognitive limitations increase susceptibility to subacute and chronic malnutrition. Nutritional requirements may change with PD progression or after surgical therapy for PD. Patients and caregivers may benefit from counseling by a dietician who is knowledgeable about the nutritional risks and needs of PD. Regularly inquire about dysphagia symptoms, and consider speech therapy consultation for clinical and modified barium-swallowing evaluations and management recommendations. Although non-oral delivery options of dopaminergic therapy are increasing, severe dysphagia may warrant percutaneous endoscopic gastrostomy tube placement for nutritional support and more reliable PD medication dosing. Analyze vitamin B(12) and D concentrations at regular intervals. Both vitamins are frequently deficient in elderly persons but may not be routinely checked by primary care physicians. Record over-the-counter and nutritional supplement medications at each visit, and assist patients in periodically re-evaluating their potential benefits, side effects, drug interactions, and costs. To date, clinical trials of antioxidant vitamins and nutritional supplements have provided insufficient evidence to support routine use for PD in the clinic. Data from several clinical trials of antioxidant vitamins/nutritional supplements are expected in the near future. Consider altering medication dosing in relation to meals to help with mild to moderate motor fluctuations. Patients with severe motor fluctuations may benefit from adapting the 5:1 carbohydrate-to-protein ratio in their daily meals and snacks. Following a "protein

  17. Connectivity Changes in Parkinson's Disease.

    PubMed

    Cerasa, Antonio; Novellino, Fabiana; Quattrone, Aldo

    2016-10-01

    Parkinson's disease (PD) is a chronic and progressive movement disorder of the central nervous system characterized by widespread alterations in several non-motor aspects such as mood, sleep, olfactory, and cognition in addition to motor dysfunctions. Advanced neuroimaging using functional connectivity reconstruction of the human brain has provided a vast knowledge on the pathophysiological mechanisms underlying this disorder, but this, however, does not cover the overall inter-/intra-individual variability of PD phenotypes. The present review is aimed at discussing to what extent the evidence provided by group-based neuroimaging analysis in this field of study (using seed-based, network-based, or graph theory approaches) may be generalized. In particular, we summarized the literature on the application of resting-state functional connectivity studies to explore different neural correlates of motor and non-motor symptoms of PD and the neural mechanisms involved in treatment effects: effects of levodopa or deep brain stimulation. The lesson learnt from one decade of studies provides consistent evidence on the role of the altered communication between the striato-frontal pathways as a marker of PD-related motor degeneration, whereas in the non-motor domain, several missing pieces of a complex puzzle are provided. However, the main target is to present a new era of intelligent neuroimaging applications, where automated multivariate analysis of functional connectivity data may be used for moving from group-level statistical results to personalized predictions in a clinical setting. Although in its relative infancy, the evidence gathered so far suggests a new era of clinical neuroimaging is starting. PMID:27568202

  18. Psychiatric aspects of Parkinson's disease.

    PubMed

    Grover, Sandeep; Somaiya, Mansi; Kumar, Santhosh; Avasthi, Ajit

    2015-01-01

    Parkinson's disease (PD) is essentially characterized by the motor symptoms in the form of resting tremor, rigidity and bradykinesia. However, over the years it has been recognized that motor symptoms are just the "tip of the iceberg" of clinical manifestations of PD. Besides motor symptoms, PD characterized by many non-motor symptoms, which include cognitive decline, psychiatric disturbances (depression, psychosis and impulse control), sleep difficulties, autonomic failures (gastrointestinal, cardiovascular, urinary, thermoregulation) and pain syndrome. This review evaluates the various aspects of psychiatric disorders including cognitive decline and sleep disturbances in patients with PD. The prevalence rate of various psychiatric disorders is high in patients with PD. In terms of risk factors, various demographic, clinical and treatment-related variables have been shown to be associated with higher risk of development of psychiatric morbidity. Evidence also suggests that the presence of psychiatric morbidity is associated with poorer outcome. Randomized controlled trials, evaluating the various pharmacological and non-pharmacological treatments for management of psychiatric morbidity in patients with PD are meager. Available evidence suggests that tricyclic antidepressants like desipramine and nortriptyline are efficacious for management of depression. Among the antipsychotics, clozapine is considered to be the best choice for management of psychosis in patients with PD. Among the various cognitive enhancers, evidence suggest efficacy of rivastigmine in management of dementia in patients with PD. To conclude, this review suggests that psychiatric morbidity is highly prevalent in patients with PD. Hence, a multidisciplinary approach must be followed to improve the overall outcome of PD. Further studies are required to evaluate the efficacy of various other measures for management of psychiatric morbidity in patients with PD. PMID:25552854

  19. [The new Parkinson's disease drugs].

    PubMed

    Hasegawa, K

    2000-10-01

    The purpose of the new drugs for Parkinson's disease is control of the long-term levodopa treatment syndromes, especially wearing-off phenomenon and dyskinesia. Therefore, they show long T1/2. Most of them are classified into dopamine agonists. Others are monoamine oxidase B inhibitor and cathecole-o-methyltransferase inhibitor. Marketed dopamine agonists are bromocriptine, pergolide, talipexole, and cabergoline in Japan. Except talipexole, they are all ergot alkaloid derivatives. Their affinity for dopamine receptor is D2 group, and their T1/2 are longer than levodopa. Bromocriptine is an oldest dopamine agonist. Other 3 drugs and bromocriptine had made each other double blinded cross over trial previously. The result of double blinded studies show that their efficacy for PD treatment were equal, 40-50% patients with PD. However, in clinical usage, some difference is observed as described below. Efficacy of pergolide is strong compared with bromocriptine; however, pergolide is easy to arise dyskinesia. Talipexole is strong in the hypnosis effect. As for cabergoline, it takes long time to show medical effect, so that it is expected to control wearing-off phenomenon. Monoamine oxidase B inhibitor, Selegiline, is useful as an economizer effect to levodopa. As for the cathechole-o-methyltransferase inhibitor (COMT-I) will be make double-blinded trial in future. The efficacy for PD treatment of COMT-I is prolonged levodopa effect for PD, so that wearing-off phenomenon will be controlled. To use these drugs successfully is important with the treatment of PD. In the future, the development of the cause therapy in addition to the systematic therapy is wanted. PMID:11068448

  20. The neuropsychiatry of Parkinson's disease.

    PubMed

    Lauterbach, E C

    2005-06-01

    The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments. PMID:16175159

  1. Cognitive training in Parkinson disease

    PubMed Central

    Leung, Isabella H.K.; Walton, Courtney C.; Hallock, Harry; Lewis, Simon J.G.; Valenzuela, Michael

    2015-01-01

    Objective: To quantify the effects of cognitive training (CT) on cognitive and behavioral outcome measures in patients with Parkinson disease (PD). Methods: We systematically searched 5 databases for randomized controlled trials (RCTs) of CT in patients with PD reporting cognitive or behavioral outcomes. Efficacy was measured as standardized mean difference (Hedges g) of post-training change. Results: Seven studies encompassing 272 patients with Hoehn & Yahr Stages 1–3 were included. The overall effect of CT over and above control conditions was small but statistically significant (7 studies: g = 0.23, 95% confidence interval [CI] 0.014–0.44, p = 0.037). True heterogeneity across studies was low (I2 = 0%) and there was no evidence of publication bias. Larger effect sizes were noted on working memory (4 studies: g = 0.74, CI 0.32–1.17, p = 0.001), processing speed (4 studies: g = 0.31, CI 0.01–0.61, p = 0.04), and executive function (5 studies: g = 0.30, CI 0.01–0.58, p = 0.042), while effects on measures of global cognition (4 studies), memory (5 studies), visuospatial skills (4 studies), and depression (5 studies), as well as attention, quality of life, and instrumental activities of daily living (3 studies each), were not statistically significant. No adverse events were reported. Conclusions: Though still small, the current body of RCT evidence indicates that CT is safe and modestly effective on cognition in patients with mild to moderate PD. Larger RCTs are necessary to examine the utility of CT for secondary prevention of cognitive decline in this population. PMID:26519540

  2. Emotion and Object Processing in Parkinson's Disease

    ERIC Educational Resources Information Center

    Cohen, Henri; Gagne, Marie-Helene; Hess, Ursula; Pourcher, Emmanuelle

    2010-01-01

    The neuropsychological literature on the processing of emotions in Parkinson's disease (PD) reveals conflicting evidence about the role of the basal ganglia in the recognition of facial emotions. Hence, the present study had two objectives. One was to determine the extent to which the visual processing of emotions and objects differs in PD. The…

  3. Post-encephalitic Parkinsonism: current experience

    PubMed Central

    Rail, David; Scholtz, Carl; Swash, Michael

    1981-01-01

    The diagnosis of post-encephalitic Parkinsonism is rarely entertained today. In this paper we discuss eight recent patients, six of whom presented in the last 20 years, that conform to the diagnosis of encephalitis lethargica. The clinical features by which the diagnosis may be made are defined so that a contemporary definition of this disorder may be attained. Images PMID:7299406

  4. Neuronal intranuclear inclusion disease and juvenile parkinsonism.

    PubMed

    O'Sullivan, J D; Hanagasi, H A; Daniel, S E; Tidswell, P; Davies, S W; Lees, A J

    2000-09-01

    Juvenile parkinsonism (onset age <20 yrs) is uncommon and few cases with neuropathologic confirmation have been reported. We present the case of a 17-year-old boy who presented with asymmetric arm tremor and bulbar symptoms. His paternal great aunt had parkinsonism with onset at age 22 years. Examination revealed parkinsonism in the absence of additional neurologic signs except for delayed pupillary responses to light. He responded well to levodopa but developed motor fluctuations and disabling dyskinesias after 3 years of treatment. Following attempted withdrawal of levodopa at age 24 years, he developed severe aspiration pneumonia complicated by cardiorepiratory arrests and he died 6 months later. At autopsy, the dominant histologic feature was wide-spread neuronal hyaline intranuclear inclusions. Neuronal depletion was observed in the substantia nigra, locus ceruleus, and, to a lesser extent, in the frontal cortex, and inclusions were particularly prominent in these areas. Inclusions were immunoreactive for ubiquitin and were typical of those seen in neuronal intranuclear inclusion disease (NIID), a rare, multisytem neurodegenerative disease. NIID should be considered in the differential diagnosis of juvenile parkinsonism. A link between NIID and hereditary neurodegenerative disorders characterized by expanded polyglutamine tracts is supported by the similar appearance of intranuclear inclusions in both conditions and by a family history in some cases of NIID. PMID:11009211

  5. Voice Onset Time in Parkinson Disease

    ERIC Educational Resources Information Center

    Fischer, Emily; Goberman, Alexander M.

    2010-01-01

    Research has found that speaking rate has an effect on voice onset time (VOT). Given that Parkinson disease (PD) affects speaking rate, the purpose of this study was to examine VOT with the effect of rate removed (VOT ratio), along with the traditional VOT measure, in individuals with PD. VOT and VOT ratio were examined in 9 individuals with PD…

  6. Midlife migraine and late-life parkinsonism

    PubMed Central

    Ross, G. Webster; Sigurdsson, Sigurdur; Garcia, Melissa; Gudmundsson, Larus S.; Sveinbjörnsdóttir, Sigurlaug; Wagner, Amy K.; Gudnason, Vilmundur; Launer, Lenore J.

    2014-01-01

    Objective: In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED). Methods: The AGES-Reykjavik cohort (born 1907–1935) has been followed since 1967. Headaches were classified based on symptoms assessed in middle age. From 2002 to 2006, 5,764 participants were reexamined to assess symptoms of parkinsonism, diagnosis of Parkinson disease (PD), family history of PD, and RLS/WED. Results: Subjects with midlife migraine, particularly migraine with aura (MA), were in later life more likely than others to report parkinsonian symptoms (odds ratio [OR]MA = 3.6 [95% CI 2.7–4.8]) and diagnosed PD (ORMA = 2.5 [95% CI 1.2–5.2]). Women with MA were more likely than others to have a parent (ORMA = 2.26 [95% CI 1.3–4.0]) or sibling (ORMA = 1.78 [95% CI 1.1–2.9]) with PD. Late-life RLS/WED was increased for headache generally. Associations were independent of cardiovascular disease and MRI-evident presumed ischemic lesions. Conclusions: These findings suggest there may be a common vulnerability to, or consequences of, migraine and multiple indicators of parkinsonism. Additional genetic and longitudinal observational studies are needed to identify candidate pathways that may account for the comorbid constellation of symptoms. PMID:25230997

  7. Parkinson's Disease: A Thalamostriatal Rebalancing Act?

    PubMed

    Tritsch, Nicolas X; Carter, Adam G

    2016-02-17

    Motor impairments in Parkinson's disease are thought to result from hypoactivation of striatal projection neurons in the direct pathway. In this issue of Neuron, Parker et al. (2016) report that dopamine depletion selectively weakens thalamic but not cortical afferents onto these neurons, implicating the thalamus as playing a key role in Parkinsonian motor symptoms. PMID:26889806

  8. NIH Research: Advances in Parkinson's Disease Research

    MedlinePlus

    ... fundamental contributions to the understanding of nervous system development. Neurological disorders—such as Parkinson's disease (PD)—strike an estimated 50 million Americans each year, exacting an incalculable personal toll and an annual economic cost of hundreds of billions of dollars in ...

  9. [Cognitive impairment in Parkinson's disease].

    PubMed

    Tachibana, Hisao

    2013-01-01

    Cognitive impairment is a common finding in Parkinson's disease (PD), even in the early stages. The concept of mild cognitive impairment (MCI) in PD was recently formalized with diagnosis being reached after impairments in neuropsychological tasks become significant in at least one domain. The brain profile of cognitive deficits involves executive functions (e. g., planning, set shifting, set maintenance, problem solving), attention and memory function. Memory deficits are characterized by impairments in delayed recall, temporal ordering and conditional associate learning. PD patients demonstrate relatively preserved recognition. Visuospatial dysfunctions have also been reported, while language is largely preserved. The existence of two distinct mild cognitive syndromes has also been suggested. One of these affects mainly the frontostriatal executive deficits that are modulated by dopaminergic medications and by a genetically determined level of prefrontal cortex dopamine release. The other affects the more-posterior cortical abilities, such as visuospatial and memory functions, and is suggested to be associated with an increased risk for conversion to dementia. Cross-sectional studies have commonly reported dementia in 20-30% of PD patients, although the 8-year cumulative incidence of dementia may be as high as 78%. Factors associated with dementia in PD are age at onset, age at the time of examination, akinetic-rigid form PD, depression, hallucination, rapid eye movement sleep behavioral disorder and severe olfactory deficits. Clinical features generally involve the same type of deficits as those found in MCI patients, which are more severe and more extensive. The phenomenology of the dementia syndrome is similar to that seen in dementia with Lewy bodies, and clinicopathological correlation studies have revealed varying results with regard to neurochemical deficits and the pathological substrate underlying cognitive impairment and dementia. Early cognitive

  10. [James Parkinson (1755-1824) revisited].

    PubMed

    Poirier, Jacques

    2013-03-01

    The name of Parkinson is universally famous because of the eponymous disease. But as a man, James Parkinson (1755-1824), is poorly known. He was born, married and passed away in his St-Leonard parish in Shoreditch (London). After having studied Latin, Greek, natural philosophy, and stenography (shorthand), which he considered as the basic tools of any doctor, he studied for six months at the London Hospital Medical College, and served his apprenticeship as an apothecary-surgeon with his father for six years. Then he was qualified as a surgeon in 1784 at the age of 29 years. His activity has been deployed in three areas: 1) medicine, 2) political activism and social reformism, 3) paleontology and oryctology. As a physician, Parkinson has published several books, the most important concerned paralysis agitans (future Parkinson's disease), gout, complications of lightning (future Lichtenberg figures and keraunoparalysis), acute appendicitis (with his son John Parkinson) and hernias (diagnosis, development, dangers of hernia ruptures, and design of a simple truss). Its ideological and political commitment was manifested by joining two secret societies and publishing numerous pamphlets, many of which are signed by the pseudonym Old Hubert; he campaigned for a better representation of the people in Parliament, for greater social justice, for the defense and recognition of the rights of the poor, the insane, the children, and against children abuse. He published a small compendium of chemistry, he was one of the thirteen members who create the British Geological Society and is recognized as one of the founders of paleontology; as was Georges Cuvier (1769-1832), he remained a strong supporter of creationism and catastrophism. Distinguished oryctologist, he gave his name to several fossils, mainly molluscs. PMID:23508322

  11. Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease.

    PubMed Central

    de Rijk, M C; Tzourio, C; Breteler, M M; Dartigues, J F; Amaducci, L; Lopez-Pousa, S; Manubens-Bertran, J M; Alpérovitch, A; Rocca, W A

    1997-01-01

    OBJECTIVES: To assess and compare the prevalence of parkinsonism and Parkinson's disease in five European populations that were surveyed with similar methodology and diagnostic criteria. METHODS: Joint analysis of five community surveys--Gironde (France), eight centres in Italy, Rotterdam (The Netherlands), Girona (Spain), and Pamplona (Spain)--in which subjects were screened in person for parkinsonism. Overall, these surveys comprised 14,636 participants aged 65 years or older. RESULTS: The overall prevalence (per 100 population), age adjusted to the 1991 European standard population, was 2.3 for parkinsonism and 1.6 for Parkinson's disease. The overall prevalence of parkinsonism for the age groups 65 to 69, 70 to 74, 75 to 79, 80 to 84, and 85 to 89 years was respectively, 0.9, 1.5, 3.7, 5.0, and 5.1. The corresponding age specific figures for Parkinson's disease were 0.6, 1.0, 2.7, 3.6, and 3.5. After adjusting for age and sex, the prevalence figures did not differ significantly across studies, except for the French study in which prevalence was lower. Prevalence was similar in men and women. Overall, 24% of the subjects with Parkinson's disease were newly detected through the surveys. CONCLUSIONS: Prevalence of both parkinsonism and Parkinson's disease increased with age, without significant differences between men and women. There was no convincing evidence for differences in prevalence across European countries. A substantial proportion of patients with Parkinson's disease went undetected in the general population. PMID:9010393

  12. Michael J. Fox: Spurring Research on Parkinson's | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Parkinson's Disease Michael J. Fox: Spurring Research on Parkinson's Past ... found a richness of soul." Some celebrities with Parkinson's disease Bob Hoskins — Retired, award-winning English actor Photo ...

  13. Identification of TMEM230 mutations in familial Parkinson's disease.

    PubMed

    Deng, Han-Xiang; Shi, Yong; Yang, Yi; Ahmeti, Kreshnik B; Miller, Nimrod; Huang, Cao; Cheng, Lijun; Zhai, Hong; Deng, Sheng; Nuytemans, Karen; Corbett, Nicola J; Kim, Myung Jong; Deng, Hao; Tang, Beisha; Yang, Ziquang; Xu, Yanming; Chan, Piu; Huang, Bo; Gao, Xiao-Ping; Song, Zhi; Liu, Zhenhua; Fecto, Faisal; Siddique, Nailah; Foroud, Tatiana; Jankovic, Joseph; Ghetti, Bernardino; Nicholson, Daniel A; Krainc, Dimitri; Melen, Onur; Vance, Jeffery M; Pericak-Vance, Margaret A; Ma, Yong-Chao; Rajput, Ali H; Siddique, Teepu

    2016-07-01

    Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders. The pathogenesis of Parkinson's disease remains largely elusive. Here we report a locus for autosomal dominant, clinically typical and Lewy body-confirmed Parkinson's disease on the short arm of chromosome 20 (20pter-p12) and identify TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. Disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, with implications for understanding the pathogenic mechanism of Parkinson's disease and for developing rational therapies. PMID:27270108

  14. A mixed-methods study into ballet for people living with Parkinson's1

    PubMed Central

    Houston, Sara; McGill, Ashley

    2012-01-01

    Background: Parkinson's is a neurological disease that is physically debilitating and can be socially isolating. Dance is growing in popularity for people with Parkinson's and claims have been made for its benefits. The paper details a mixed-methods study that examined a 12-week dance project for people with Parkinson's, led by English National Ballet. Methods: The effects on balance, stability and posture were measured through the Fullerton Advanced Balance Scale and a plumb-line analysis. The value of participation and movement quality were interpreted through ethnographic methods, grounded theory and Effort analysis. Results: Triangulation of results indicates that people were highly motivated, with 100% adherence, and valued the classes as an important part of their lives. Additionally, results indicated an improvement in balance and stability, although not in posture. Conclusions: Dancing may offer benefit to people with Parkinson's through its intellectual, artistic, social and physical aspects. The paper suggests that a range of research methods is fundamental to capture the importance of multifaceted activity, such as dance, to those with Parkinson's. PMID:23805165

  15. Increased risk of parkinsonism associated with welding exposure

    PubMed Central

    Racette, Brad A.; Criswell, Susan R.; Lundin, Jessica I.; Hobson, Angela; Seixas, Noah; Kotzbauer, Paul T.; Evanoff, Bradley A.; Perlmutter, Joel S.; Zhang, Jing; Sheppard, Lianne; Checkoway, Harvey

    2013-01-01

    Objective Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. Methods This was a cross-sectional and nested case–control study to investigate the prevalence and phenotype of parkinsonism among 811 shipyard and fabrication welders recruited from trade unions. Two reference groups included 59 non-welder trade workers and 118 newly diagnosed, untreated idiopathic PD patients. Study subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as welders with UPDRS3 score ≥15. Normal was defined as UPDRS3 < 6. Exposure was classified as intensity adjusted, cumulative years of welding. Adjusted prevalence ratios for parkinsonism were calculated in relation to quartiles of welding years. Results The overall prevalence estimate of parkinsonism was 15.6% in welding exposed workers compared to 0% in the reference group. Among welders, we observed a U-shaped dose–response relation between weighted welding exposure-years and parkinsonism. UPDRS3 scores for most domains were similar between welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except for greater frequency of rest tremor and asymmetry in PD patients. Conclusion This work-site based study among welders demonstrates a high prevalence of parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that overlaps substantially with PD. PMID:22975422

  16. Atropinic (Anticholinergic) Burden in Parkinson's Disease.

    PubMed

    De Germay, Sibylle; Montastruc, Jean-Louis; Rousseau, Vanessa; Chebane, Leila; Bondon-Guitton, Emmanuelle; Moulis, Florence; Durrieu, Genevieve; Bagheri, Haleh; Rascol, Olivier; Pariente, Antoine; Bégaud, Bernard; Montastruc, François

    2016-05-01

    Use of atropinic drugs remains controversial in Parkinson's disease (PD) because there is insufficient evidence about their efficacy and they can induce serious adverse drug reactions. Atropinic risk scales were developed to help to identify atropinic drugs in prescription forms and to evaluate their burden in clinical practice. In the present review, we discuss the few studies investigating atropinic burden in PD and present the results of our study indicating that atropinic drugs are still widely prescribed in PD (almost 3 of 5 prescriptions) with a clinically significant atropinic burden in around 1 of 6 PD patients. Drugs mainly responsible for high values of atropinic burden were those used for nonmotor symptoms. Clinically significant atropinic burdens were mainly induced by associations of several "low-risk" drugs. Physicians must be aware that in addition to classical atropinic antiparkinsonian drugs, many others (psychotropics) can contribute to increased atropinic burden in PD patients. © 2016 International Parkinson and Movement Disorder Society. PMID:27028036

  17. Therapeutic interventions in parkinsonism: Corticobasal degeneration.

    PubMed

    Marsili, Luca; Suppa, Antonio; Berardelli, Alfredo; Colosimo, Carlo

    2016-01-01

    Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder resulting from pathological accumulation of tau protein and is included in the spectrum of Atypical Parkinsonism. The typical clinical phenotype of CBD is characterized by the Corticobasal syndrome (CBS). In recent years it has become clear that the clinical picture of CBS may be caused by different pathological conditions, resulting in frequent misdiagnosis. CBD has high morbidity and poor prognosis with no effective therapies. In this review, we will discuss the symptomatic treatment, the palliative care and the disease modifying strategies currently in use. Symptomatic treatment in patients with CBD may sometimes be useful for improving motor (parkinsonism, dystonia and myoclonus) and non-motor (cognitive-behavioral) symptoms, but the effects are often unsatisfactory. In addition, non-pharmacological strategies and palliative care are useful integrating components of the multidisciplinary therapeutic approach for patients with CBD. Despite many efforts, a disease-modifying treatment is still unavailable for CBD. PMID:26382843

  18. Diagnosing Parkinson's Diseases Using Fuzzy Neural System

    PubMed Central

    Abiyev, Rahib H.; Abizade, Sanan

    2016-01-01

    This study presents the design of the recognition system that will discriminate between healthy people and people with Parkinson's disease. A diagnosing of Parkinson's diseases is performed using fusion of the fuzzy system and neural networks. The structure and learning algorithms of the proposed fuzzy neural system (FNS) are presented. The approach described in this paper allows enhancing the capability of the designed system and efficiently distinguishing healthy individuals. It was proved through simulation of the system that has been performed using data obtained from UCI machine learning repository. A comparative study was carried out and the simulation results demonstrated that the proposed fuzzy neural system improves the recognition rate of the designed system. PMID:26881009

  19. Protective Mechanisms of Flavonoids in Parkinson's Disease

    PubMed Central

    Magalingam, Kasthuri Bai; Radhakrishnan, Ammu Kutty; Haleagrahara, Nagaraja

    2015-01-01

    Parkinson's disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson's disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage. Within the past decades, an explosion of research discoveries has reported on the protective mechanisms of flavonoids, which are plant-based polyphenols, in the treatment of neurodegenerative disease using both in vitro and in vivo models. In this paper, we have reviewed the literature on the neuroprotective mechanisms of flavonoids in protecting the dopaminergic neurons hence reducing the symptoms of this movement disorder. The mechanism reviewed includes effect of flavonoids in activation of endogenous antioxidant enzymes, suppressing the lipid peroxidation, inhibition of inflammatory mediators, flavonoids as a mitochondrial target therapy, and modulation of gene expression in neuronal cells. PMID:26576219

  20. Naturally- and experimentally-designed restorations of the Parkin gene deficit in autosomal recessive juvenile parkinsonism

    SciTech Connect

    Asai, Hirohide; Hirano, Makito; Kiriyama, Takao; Ikeda, Masanori; Ueno, Satoshi

    2010-01-01

    Intranuclear events due to mutations in the Parkin gene remain elusive in autosomal recessive juvenile parkinsonism (ARJP). We identified a mutant PARKIN protein in fibroblast cultures from a pair of siblings with ARJP who were homozygous for the exon 4-deleted Parkin gene. Disease was mild in one patient and debilitating in the other. The detected mutant, encoded by a transcript lacking exon 3 as well as exon 4, is an in-frame deletion that removes 121 aa, resulting in a 344-aa protein (PaDel3,4). Cell culture and transfection studies revealed negative correlations between expression levels of PaDel3,4 and those of cell cycle proteins, including cyclin E, CDK2, ppRb, and E2F-1, and demonstrated that GFP-PaDel3,4 entered nucleus and ubiquitinated cyclin E as a part of SCF{sup hSel-10} ligase complex in the patient cells. In addition, nuclear localization signal-tagged PaDel3,4 expressed in the transfected patient cells most effectively ubiquitinated cyclin E and reduced DNA damage, protecting cells from oxidative stress. Antisense-oligonucleotide treatment promoted skipping of exon 3 and thus generated PaDel3,4, increasing cell survival. Collectively, we propose that naturally- and experimentally-induced exon skipping at least partly restores the mutant Parkin gene deficit, providing a molecular basis for the development of therapeutic exon skipping.

  1. Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease.

    PubMed

    Volta, Mattia; Milnerwood, Austen J; Farrer, Matthew J

    2015-10-01

    Disease-modifying therapies that slow or halt the progression of Parkinson's disease are an unmet clinical need. Many hypotheses have been put forward to explain the pathogenesis of the disease, but none has led to the development of disease-modifying drugs. Here we focus on familial forms of late-onset parkinsonism that most closely resemble idiopathic Parkinson's disease and present a synthesis of emerging molecular advances. Genetic discoveries and mechanistic investigations have highlighted early alterations to synaptic function, endosomal maturation, and protein sorting that might lead to an intracellular proteinopathy. We propose that these cellular processes constitute one pathway to pathogenesis and suggest that neuroprotection, as an adjunct to current symptomatic treatments, need not remain an elusive goal. PMID:26376970

  2. A feeding mechanism for Parkinson's disease patients.

    PubMed

    Broadhurst, M; Stammers, C W

    1988-01-01

    A pivotted four-bar chain mechanism has been studied and built as a feeding aid for Parkinson's patients. This system provides a good feeding path. Guidance is by means of a spring restrained sliding handle. The tremor exhibited by three patients was established in constant force tests. Shake tests using simulated inputs spanning the frequency range indicated (2.5 Hz-6 Hz) established the vibration isolation properties of the system. PMID:3361598

  3. MDS clinical diagnostic criteria for Parkinson's disease.

    PubMed

    Postuma, Ronald B; Berg, Daniela; Stern, Matthew; Poewe, Werner; Olanow, C Warren; Oertel, Wolfgang; Obeso, José; Marek, Kenneth; Litvan, Irene; Lang, Anthony E; Halliday, Glenda; Goetz, Christopher G; Gasser, Thomas; Dubois, Bruno; Chan, Piu; Bloem, Bastiaan R; Adler, Charles H; Deuschl, Günther

    2015-10-01

    This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances. PMID:26474316

  4. Stereotactic ventral pallidotomy for Parkinson's disease.

    PubMed

    Dogali, M; Fazzini, E; Kolodny, E; Eidelberg, D; Sterio, D; Devinsky, O; Berić, A

    1995-04-01

    Eighteen patients with medically intractable Parkinson's disease that was characterized by bradykinesia, rigidity, and marked "on-off" fluctuations underwent stereotactic ventral pallidotomy under local anesthesia. Targeting was aided by anatomic coordinates derived from the MRI, intraoperative cell recordings, and electrical stimulation prior to lesioning. A nonsurgically treated group of seven similarly affected individuals was also followed. Assessment of motor function was made at baseline and at 3-month intervals for 1 year. Following the lesioning, patients improved in bradykinesia, rigidity, resting tremor, and balance with resolution of medication-induced contralateral dyskinesia. When compared with preoperative baseline, all quantifiable test scores after surgery improved significantly with the patients off medications for 12 hours: UPDRS by 65%, and CAPIT subtest scores on the contralateral limb by 38.2% and the ipsilateral limb by 24.2%. Walk scores improved by 45%. Medication requirements were unchanged, but the patients who had had surgery were able to tolerate larger doses because of reduced dyskinesia. Ventral pallidotomy produces statistically significant reduction in parkinsonism and contralateral "on" dyskinesia without morbidity or mortality and with a short hospitalization in Parkinson's disease patients for whom medical therapy has failed. PMID:7723966

  5. Intrinsic and extrinsic psychosis in Parkinson's disease.

    PubMed

    Wolters, E C

    2001-09-01

    Direct and indirect signs and symptoms of Parkinson's disease are a major cause of disability in the elderly. Intrinsic symptoms comprise not only the well-known clinical hallmarks of this disease with motor behavioral abnormalities, such as bradykinesia, hypokinesia, rigidity and tremor, but also autonomic failure with orthostatic hypotension, urinal incontinence and impotence as well as non-motor behavioral abnormalities: mental dysfunction characterized by mood disorders, cognitive dysfunction and, sporadically, delusions and hallucinations. These symptoms are caused by a progressive abnormal degeneration of the dopamine (DA) producing cells in the substantia nigra (SN) and ventral tegmentum area (VTA) in combination with an interindividual fluctuating degree of decay in the noradrenergic (locus coeruleus), cholinergic forebrain (nucleus basalis of Meynert) and serotoninergic (dorsal raphe nuclei) systems. Extrinsic symptoms, induced by pharmacotherapy, mainly manifest with (un)predictable motor response fluctuations and dopaminomimetic psychosis. Psychological and psychiatric symptoms in Parkinson's disease (PD) are important predictors of the patient's quality of life. As these symptoms are potentially treatable, identification is of major clinical importance both for the patients and their caregivers and may enable to maintain Parkinson's disease patients at home for a longer period. PMID:11697684

  6. Instruments for holistic assessment of Parkinson's disease.

    PubMed

    Martinez-Martin, Pablo

    2013-04-01

    Assessment of Parkinson's disease is a complex matter as a consequence of the variety of manifestations and complications that can be present in a patient. Although a really holistic assessment is probably a utopia, a comprehensive evaluation is possible using a combination of measures completed by health professionals, patients and/or caregivers. In PD, main domains requiring assessment include motor impairment, motor complications, non-motor symptoms, disability, and patient-reported outcomes. Such scales like the Movement Disorder Society-Unified Parkinson's Disease Rating Scale and the battery of Scales for Outcomes in Parkinson's disease (SCOPA) provide a wide information on the most relevant aspects of the disease. Hoehn and Yahr staging, global impression, and quality of life measures furnish summarized whole evaluations and comprehensive non-motor symptom assessments help to identify and evaluate this kind of manifestations. This article shows a pragmatic review of common instruments (rating scales and questionnaires) usable for a comprehensive assessment of PD and provides information about sources for guiding the selection of measures and outcome analyses. PMID:23474821

  7. Parkinsonism: a rare manifestation of craniopharyngioma.

    PubMed

    Parvaresh, Mansour; Azar, Maziar; Ghalaenovi, Hossein; Fattahi, Arash

    2015-01-01

    Craniopharyngioma is a non-glial, non-malignant intracranial tumor of ectodermal origin, which arises from a remnant of Rathke's pouch. This tumor accounts for 5.6 to 13% of intracranial tumors in children. This paper discusses a case of craniopharyngioma in a five-year-old boy. An MRI scan of his brain showed a huge sella and supra sella cystic-solid lesion that had invaded the prepontine and interpeduncular cisterns, filling of 3rd ventricle and hydrocephalus. The patient operated via interhemispheric subfrontal through lamina terminalis and the tumor dissected from all part of brain stem and total resection achieved. After surgery Parkinsonism was worse for 3 days and levodopa started for 3 days. Parkinsonism was gone and after one week levodopa discontinued. This case practically implied that decompression of mass effect of tumor on brain stem and short-term management with levodopa can improve Parkinsonism due to midline compressive brain tumors without basal ganglia involvement. PMID:26120410

  8. New perspective on parkinsonism in frontotemporal lobar degeneration.

    PubMed

    Park, Hee Kyung; Chung, Sun J

    2013-05-01

    Frontotemporal dementia (FTD) is the second most common type of presenile dementia. Three clinical prototypes have been defined; behavioral variant FTD, semantic dementia, and progressive nonfluent aphasia. Progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease may possess clinical and pathological characteristics that overlap with FTD, and it is possible that they may all belong to the same clinicopathological spectrum. Frontotemporal lobar degeneration (FTLD) is a clinicopathological syndrome that encompasses a heterogenous group of neurodegenerative disorders. Owing to the advancement in the field of molecular genetics, diagnostic imaging, and pathology, FTLD has been the focus of great interest. Nevertheless, parkinsonism in FTLD has received relatively less attention. Parkinsonism is found in approximately 20-30% of patients in FTLD. Furthermore, parkinsonism can be seen in all FTLD subtypes, and some patients with familial and sporadic FTLD can present with prominent parkinsonism. Therefore, there is a need to understand parkinsonism in FTLD in order to obtain a better understanding of the disease. With regard to the clinical characteristics, the akinetic rigid type of parkinsonism has predominantly been described. Parkinsonism is frequently observed in familial FTD, more specifically, in FTD with parkinsonism linked to chromosome 17q (FTDP-17). The genes associated with parkinsonism are microtubule associated protein tau (MAPT), progranulin (GRN or PGRN), and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. The neural substrate of parkinsonism remains to be unveiled. Dopamine transporter (DAT) imaging revealed decreased uptake of DAT, and imaging findings indicated atrophic changes of the basal ganglia. Parkinsonism can be an important feature in FTLD and, therefore, increased attention is needed on the subject. PMID:24868417

  9. New Perspective on Parkinsonism in Frontotemporal Lobar Degeneration

    PubMed Central

    Park, Hee Kyung; Chung, Sun J.

    2013-01-01

    Frontotemporal dementia (FTD) is the second most common type of presenile dementia. Three clinical prototypes have been defined; behavioral variant FTD, semantic dementia, and progressive nonfluent aphasia. Progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease may possess clinical and pathological characteristics that overlap with FTD, and it is possible that they may all belong to the same clinicopathological spectrum. Frontotemporal lobar degeneration (FTLD) is a clinicopathological syndrome that encompasses a heterogenous group of neurodegenerative disorders. Owing to the advancement in the field of molecular genetics, diagnostic imaging, and pathology, FTLD has been the focus of great interest. Nevertheless, parkinsonism in FTLD has received relatively less attention. Parkinsonism is found in approximately 20–30% of patients in FTLD. Furthermore, parkinsonism can be seen in all FTLD subtypes, and some patients with familial and sporadic FTLD can present with prominent parkinsonism. Therefore, there is a need to understand parkinsonism in FTLD in order to obtain a better understanding of the disease. With regard to the clinical characteristics, the akinetic rigid type of parkinsonism has predominantly been described. Parkinsonism is frequently observed in familial FTD, more specifically, in FTD with parkinsonism linked to chromosome 17q (FTDP-17). The genes associated with parkinsonism are microtubule associated protein tau (MAPT), progranulin (GRN or PGRN), and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. The neural substrate of parkinsonism remains to be unveiled. Dopamine transporter (DAT) imaging revealed decreased uptake of DAT, and imaging findings indicated atrophic changes of the basal ganglia. Parkinsonism can be an important feature in FTLD and, therefore, increased attention is needed on the subject. PMID:24868417

  10. Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

    PubMed Central

    Barrett, MJ; Hagenah, J; Dhawan, V; Peng, S; Stanley, K; Raymond, D; Deik, A; Gross, SJ; Schreiber-Agus, N; Mirelman, A; Marder, K; Ozelius, LJ; Eidelberg, D; Bressman, SB; Saunders-Pullman, R

    2012-01-01

    Background Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. Methods To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [18F]-fluorodeoxyglucose or [18F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. Results Parkinson disease subjects with heterozygous GBA mutations (n=23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n=34, aSNmax=0.30 vs. 0.18, p=0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n=4, aSNmax=0.27); subjects without LRRK2 or GBA mutations (n=32, aSNmax=0.27); LRRK2 heterozygotes/homozyogotes without GBA mutations (n=27, aSNmax=0.28); and GBA heterozygotes/LRRK2 heterozygotes (n=4, aSNmax=0.32, overall p=0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [18F]-fluorodeoxyglucose (n=3) and [18F]-fluorodopa (n=2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. Conclusions Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects. PMID:23062841

  11. Abnormal Bidirectional Plasticity-Like Effects in Parkinson's Disease

    ERIC Educational Resources Information Center

    Huang, Ying-Zu; Rothwell, John C.; Lu, Chin-Song; Chuang, Wen-Li; Chen, Rou-Shayn

    2011-01-01

    Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that…

  12. "PINK1"-Linked Parkinsonism Is Associated with Lewy Body Pathology

    ERIC Educational Resources Information Center

    Samaranch, Lluis; Lorenzo-Betancor, Oswaldo; Arbelo, Jose M.; Ferrer, Isidre; Lorenzo, Elena; Irigoyen, Jaione; Pastor, Maria A.; Marrero, Carmen; Isla, Concepcion; Herrera-Henriquez, Joanna; Pastor, Pau

    2010-01-01

    Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed…

  13. Visual dysfunction in patients with Parkinson's disease and essential tremor.

    PubMed

    Štenc Bradvica, Ivanka; Bradvica, Mario; Matić, Suzana; Reisz-Majić, Patricia

    2015-02-01

    The aim of this study was to determine the specificity and sensitivity of the Pelli-Robson and Ishihara diagnostic methods in differing Parkinson's disease from essential tremor compared to DaTSCAN (dopamine transporter scan) findings. The intention was to investigate whether visual dysfunction appears in the early state of Parkinson's disease. Therefore, we included patients with the symptomatology of parkinsonism lasting between 6 and 12 months. The study included 164 patients of which 59 (36.0%) suffered from Parkinson's disease, 51 (31.1%) from essential tremor, and 54 (32.9%) healthy patients which presented the control group. The specificity of Pelli-Robson test in confirming Parkinson's disease was 53% and the sensitivity 81.4%. The specificity of Ishihara test in confirming Parkinson's disease was 88.2%, and sensitivity 55.9%. We found that the colour and contrast dysfunction are present as the earliest symptoms of Parkinson's disease. In this study the Pelli-Robson test is highly sensitive and the Ishihara tables are highly specific in the differential diagnosis between Parkinson's disease and essential tremor, but neither of these methods fulfils the criteria for the validity of a test. We suggest performing both of these methods to evaluate which patients are indicated for DaTSCAN. PMID:25164787

  14. Dopaminergic modulation of memory and affective processing in Parkinson depression.

    PubMed

    Blonder, Lee X; Slevin, John T; Kryscio, Richard J; Martin, Catherine A; Andersen, Anders H; Smith, Charles D; Schmitt, Frederick A

    2013-11-30

    Depression is common in Parkinson's disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson's disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson's disease participated. Ten of these patients were depressed according to DSM IV criteria. Results revealed a statistically significant interaction between depression and medication status on three measures of verbal memory and a facial affect naming task. In all cases, depressed Parkinson's patients performed significantly more poorly while on dopaminergic medication than while off. The opposite pattern emerged for the non-depressed Parkinson's group. The administration of dopaminergic medication to depressed Parkinson patients may carry unintended risks. PMID:23838419

  15. Pink Light on Mitochondria in Autoimmunity and Parkinson Disease.

    PubMed

    Mantegazza, Adriana R; Marks, Michael S

    2016-07-12

    Mitochondrial dysfunction and T cell autoimmunity have been independently implicated in Parkinson disease pathogenesis. In a recent publication in Cell, Matheoud et al. (2016) link them by describing a new mechanism, activated in familial forms of Parkinson disease, in which mitochondrial proteins are processed for recognition by CD8+ T cells. PMID:27411006

  16. Neural Control of Walking in People with Parkinsonism.

    PubMed

    Peterson, D S; Horak, F B

    2016-03-01

    People with Parkinson's disease exhibit debilitating gait impairments, including gait slowness, increased step variability, and poor postural control. A widespread supraspinal locomotor network including the cortex, cerebellum, basal ganglia, and brain stem contributes to the control of human locomotion, and altered activity of these structures underlies gait dysfunction due to Parkinson's disease. PMID:26889015

  17. The Effects of Levodopa on Word Intelligibility in Parkinson's Disease

    ERIC Educational Resources Information Center

    De Letter, Miet; Santens, Patrick; Van Borsel, John

    2005-01-01

    Dysarthria is a common manifestation in patients with idiopathic Parkinson's disease. This study investigated the effects of levodopa on intelligibility in patients with Parkinson's disease. Ten participants were tested during on- and off-states using the Yorkston and Beukelman intelligibility test (1980). Intelligibility as scored by a panel of…

  18. Inverse Association of Parkinson Disease With Systemic Lupus Erythematosus

    PubMed Central

    Liu, Feng-Cheng; Huang, Wen-Yen; Lin, Te-Yu; Shen, Chih-Hao; Chou, Yu-Ching; Lin, Cheng-Li; Lin, Kuen-Tze; Kao, Chia-Hung

    2015-01-01

    Abstract The effects of the inflammatory mediators involved in systemic lupus erythematous (SLE) on subsequent Parkinson disease have been reported, but no relevant studies have focused on the association between the 2 diseases. This nationwide population-based study evaluated the risk of Parkinson disease in patients with SLE. We identified 12,817 patients in the Taiwan National Health Insurance database diagnosed with SLE between 2000 and 2010 and compared the incidence rate of Parkinson disease among these patients with that among 51,268 randomly selected age and sex-matched non-SLE patients. A Cox multivariable proportional-hazards model was used to evaluate the risk factors of Parkinson disease in the SLE cohort. We observed an inverse association between a diagnosis of SLE and the risk of subsequent Parkinson disease, with the crude hazard ratio (HR) being 0.60 (95% confidence interval 0.45–0.79) and adjusted HR being 0.68 (95% confidence interval 0.51–0.90). The cumulative incidence of Parkinson disease was 0.83% lower in the SLE cohort than in the non-SLE cohort. The adjusted HR of Parkinson disease decreased as the follow-up duration increased and was decreased among older lupus patients with comorbidity. We determined that patients with SLE had a decreased risk of subsequent Parkinson disease. Further research is required to elucidate the underlying mechanism. PMID:26579824

  19. Compulsive singing: another aspect of punding in Parkinson's disease.

    PubMed

    Bonvin, Christophe; Horvath, Judit; Christe, Blaise; Landis, Theodor; Burkhard, Pierre R

    2007-11-01

    We report on two patients with advanced Parkinson's disease who were exhibiting a peculiar and stereotyped behavior characterized by an irrepressible need to sing compulsively when under high-dose dopamine replacement therapy. Sharing many features with punding, this singing behavior is proposed as a distinct manifestation of the dopamine dysregulation syndrome in Parkinson's disease. PMID:17696122

  20. Exercise Training and Parkinson's Disease: Placebo or Essential Treatment?

    ERIC Educational Resources Information Center

    Reuter, Iris; Engelhardt, Martin

    2002-01-01

    Exercise training is often recommended for people with Parkinson's disease, though there is debate about the pathophysiologic cause of impaired movement in Parkinsonism which makes it difficult to develop a specific exercise treatment for symptoms that include hypokinesia, tremor, and muscular rigidity. Most published studies show a benefit of…

  1. Parkinson's Disease Research at NIH | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease Research at NIH Past Issues / Winter 2014 Table ... of its research: MedlinePlus . www.medlineplus.gov . Type "Parkinson's disease" in the Search box. NIHSeniorHealth —Parkinson's Disease http:// ...

  2. Fatigue in Parkinson disease: an integrative review.

    PubMed

    Bruno, Amy E; Sethares, Kristen A

    2015-06-01

    Fatigue, one of the most prevalent and underassessed nonmotor symptoms in patients with Parkinson disease (PD), is reported to be a major cause of disability and reduced quality of life. The purpose of this review was to systematically examine the scientific literature and report how fatigue is defined and measured and what interventions are used to treat it. A synthesis of the current literature will expose the current state of the science of fatigue in PD, propose areas for future research, and offer practice implications. An integrative review of the literature was conducted. The electronic databases CINAHL, Psychinfo, and PUBMED were searched using the keywords "Parkinson's disease," "fatigue," "definition," "mental fatigue," "physical fatigue," "measurement," "interventions," "treatment," and "methylphenidate." One hundred fourteen articles were found. Nineteen studies met review criteria. No universal definition of fatigue in PD was found, making it difficult to measure. However, central, physical, mental, and peripheral fatigues were described. Six scales were found that measure fatigue in PD; only one specific to PD, the Parkinson Fatigue Scale, measured physical fatigue. Seven studies reported interventions to treat fatigue and were categorized as medication, exercise, and alternative interventions. None of these interventions had a significant effect on fatigue. Findings showed that (a) there is a lack of a universally accepted definition of fatigue because of its subjective nature, (b) existing fatigue measurement tools do not measure all types of fatigue in PD, and (c) no intervention had a significant effect on fatigue. There is a need to define and explore fatigue further using qualitative methods. Further development of instruments to measure fatigue in women, younger onset, and older adults with PD is needed. A focus on person-centered interventions to reduce fatigue in patients with PD is a research priority. PMID:25943995

  3. The most cited works in Parkinson's disease.

    PubMed

    Ponce, Francisco A; Lozano, Andres M

    2011-02-15

    The number of citations a work has received is a measure of its impact. We identified the top cited works in Parkinson's disease. A Web of Science search was performed for articles including the keyword "Parkinson*" in the title (the asterisk was included in the search string as a wild card character). Articles with more than 400 citations, the threshold to be considered a "citation classic," were identified and analyzed. The 107 articles identified appeared in 33 different journals, with clinical articles primarily appearing in the New England Journal of Medicine and Lancet, and scientific articles primarily in Nature, Science, and the Proceedings of the National Academy of Sciences. There were 52 laboratory studies, 38 clinical studies, 12 review articles, and 5 classifications of disease. The clinical studies included evaluation of medical and surgical therapies, and the laboratory studies included gene discovery, molecular biology, and cellular biology, as well as animal models and neuropathological studies. High impact topics included deep brain stimulation, levodopa therapy and related adverse effects, MPTP-based animal studies, discovery and evaluation of genetic mutations, and pathogenesis related to oxidative degeneration. More than half of the articles identified in this study have been published in the past 20 years. Prior to 1990, highly cited articles in Parkinson's disease tended to be those that evaluated medical therapies and defined the clinical and neuropathological characteristics of the disease. Since 1990, a high proportion of the citation classics address the genetic characterization of and surgical treatments for the disease suggesting that these are the most significant recent developments and main drivers of impact in this field. PMID:21462255

  4. Technology in Parkinson's disease: Challenges and opportunities.

    PubMed

    Espay, Alberto J; Bonato, Paolo; Nahab, Fatta B; Maetzler, Walter; Dean, John M; Klucken, Jochen; Eskofier, Bjoern M; Merola, Aristide; Horak, Fay; Lang, Anthony E; Reilmann, Ralf; Giuffrida, Joe; Nieuwboer, Alice; Horne, Malcolm; Little, Max A; Litvan, Irene; Simuni, Tanya; Dorsey, E Ray; Burack, Michelle A; Kubota, Ken; Kamondi, Anita; Godinho, Catarina; Daneault, Jean-Francois; Mitsi, Georgia; Krinke, Lothar; Hausdorff, Jeffery M; Bloem, Bastiaan R; Papapetropoulos, Spyros

    2016-09-01

    The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society. PMID:27125836

  5. Evaluation of Models of Parkinson's Disease

    PubMed Central

    Jagmag, Shail A.; Tripathi, Naveen; Shukla, Sunil D.; Maiti, Sankar; Khurana, Sukant

    2016-01-01

    Parkinson's disease is one of the most common neurodegenerative diseases. Animal models have contributed a large part to our understanding and therapeutics developed for treatment of PD. There are several more exhaustive reviews of literature that provide the initiated insights into the specific models; however a novel synthesis of the basic advantages and disadvantages of different models is much needed. Here we compare both neurotoxin based and genetic models while suggesting some novel avenues in PD modeling. We also highlight the problems faced and promises of all the mammalian models with the hope of providing a framework for comparison of various systems. PMID:26834536

  6. [Undate on Current Care Guideline: Parkinson's disease].

    PubMed

    2016-01-01

    The treatment of Parkinson's disease may be initiated with dopamine agonist or MAO-B-inhibitor for people under 60-65 years of age. For older patients, the treatment may also be started with levodopa. If there are motor complications, such as on-off-symptoms, apomorphin injections can be beneficial in addition to other medications. In the case of difficult on-off-symptoms and dyskinesias in spite of optimal treatment, deep brain stimulation, duodenal levodopa infusion and apomorphine infusion should be considered. Rehabilitation can improve gait speed and balance, decrease falls and improve speech. However, with advancing disease the results are not maintained if trainino is discontinued. PMID:27044185

  7. Parkinsonism as a Complication of Bariatric Surgery

    PubMed Central

    Kamel, Walaa A.; Hashel, Jasem Y. Al; Kilany, Ayman; Altailji, Samira

    2015-01-01

    BACKGROUND: The association between Parkinsonism and BS has already been reported in only three patients worldwide. CASE SUMMARY: We report a 39-years old Kuwaiti female who presented with parkinsonian features and mononeuropathy (carpal tunnel syndrome) 3 years after a vertical sleeve gastrectomy operation. CONCLUSION: We conclude that with the increasing popularity of bariatric surgery, clinicians will need to recognize and manage neurologic complications that may appear soon after or years to decades later. Thorough evaluation is essential for any patient who has undergone bariatric surgery and develops neurologic symptoms.

  8. [Overlooked Wolff-Parkinson-White syndrome].

    PubMed

    Nielsen, Trine Skov; Dalager, Søren; Larsen, Maiken Kudahl; Jensen, Henrik Kjaerulf; Lundemose, Jytte Banner

    2010-09-13

    An autopsy in a 28-year-old man did not explain the cause of sudden unexpected death. However, a history of episodes with tachycardia and dizziness and a reassessed previous electrocardiogram exhibiting ventricular pre-excitation was consistent with Wolff-Parkinson-White (WPW) syndrome. In this patient we believe that the occurrence of atrial fibrillation caused sudden cardiac death from ventricular fibrillation due to a short refractory period of an accessory atrioventricular pathway and a very rapid ventricular rate in atrial fibrillation. PMID:20836960

  9. Parkinson's Disease: Is It a Toxic Syndrome?

    PubMed Central

    Gad ELhak, Seham A.; Ghanem, Abdel Aziz A.; AbdelGhaffar, Hassan; El Dakroury, Sahar; Salama, Mohamed M.

    2010-01-01

    Parkinson's disease (PD) is one of the neurodegenerative diseases which we can by certainty identify its pathology, however, this confidence disappeares when talking about the cause. A long history of trials, suggestions, and theories tried linking PD to a specific causation. In this paper, a new suggestion is trying to find its way, could it be toxicology? Can we—in the future—look to PD as an occupational disease, in fact, many clues point to the possible toxic responsibility—either total or partial—in causing this disease. Searching for possible toxic causes for PD would help in designing perfect toxic models in animals. PMID:21152209

  10. Non-motor symptoms in Parkinson's disease.

    PubMed

    Pfeiffer, Ronald F

    2016-01-01

    With the growing awareness of the presence of non-motor symptoms in Parkinson's disease (PD) has come the realization that these non-motor features play a tremendously important, and sometimes dominant, role in the management and even the diagnosis of the disorder. Despite this, a reluctance to formally address and treat the non-motor symptoms of PD remains and quality of life for PD patients suffers. This review provides an overview of the impact non-motor symptoms have on persons with PD, along with a brief description of some of the more common non-motor features of PD. PMID:26372623

  11. Clinical correlates of raphe serotonergic dysfunction in early Parkinson's disease.

    PubMed

    Qamhawi, Zahi; Towey, David; Shah, Bina; Pagano, Gennaro; Seibyl, John; Marek, Kenneth; Borghammer, Per; Brooks, David James; Pavese, Nicola

    2015-10-01

    Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous

  12. Non motor subtypes and Parkinson's disease.

    PubMed

    Sauerbier, Anna; Jenner, Peter; Todorova, Antoniya; Chaudhuri, K Ray

    2016-01-01

    Non motor symptoms (NMS) represent a significant burden in Parkinson's disease (PD) with numerous studies highlighting the importance of NMS both in "pre-motor" phase of PD as well as throughout the course of disease. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent clinical and neurobiological research suggests the existence of discrete non motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific "clusters of NMS dominant PD" using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. In this review we report on specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. A proposal for several NMS subtypes are reported combining clinical reports with, where possible, evidence base supporting probable biomarkers. PMID:26459660

  13. Testosterone improves motor function in Parkinson's disease.

    PubMed

    Mitchell, E; Thomas, D; Burnet, R

    2006-01-01

    In Parkinson's disease (PD) there is increasing evidence that sex steroids such as estradiol and testosterone modulate, either as a positive or negative effect, the clinical expression of a variety of movement disorders involving the nigrostriatum. Testosterone deficiency is common in the older male population and has an increased prevalence in parkinsonian patients. Testosterone therapy has been shown to improve the non-motor symptoms of PD but evidence for a direct effect of testosterone on motor symptoms is lacking. This case report demonstrates a significant improvement in the resting tremor and fine motor control after testosterone administration in a parkinsonian patient with testosterone deficiency (1 nmol/L). Motor symptom change was shown by serial assessment of the patient's handwriting, self-reporting using the Unified Parkinson's Disease Rating Scale and measurement of resting tremor amplitude by an accelerometer. The improvement in motor symptoms correlated with serum testosterone levels. The use of testosterone replacement in those men with decreased levels may improve the motor symptoms as well as increase general wellbeing. PMID:16410216

  14. Eye Movements in Ephedrone-Induced Parkinsonism

    PubMed Central

    Megrelishvili, Marika; Sieger, Tomáš; Matoušková, Olga; Okujava, Michael; Brožová, Hana; Nikolai, Tomáš; Hanuška, Jaromír; Kapianidze, Mariam; Mikeladze, Nina; Botchorishvili, Nazi; Khatiashvili, Irine; Janelidze, Marina; Serranová, Tereza; Fiala, Ondřej; Roth, Jan; Bergquist, Jonas; Jech, Robert; Rivaud-Péchoux, Sophie; Gaymard, Bertrand; Růžička, Evžen

    2014-01-01

    Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinson's disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro- and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese-induced damage to the basal ganglia, reflecting their role in oculomotor system. PMID:25117825

  15. Quantification of rigidity in Parkinson's disease.

    PubMed

    Sepehri, Behrooz; Esteki, Ali; Ebrahimi-Takamjani, Esmaeal; Shahidi, Golam-Ali; Khamseh, Fatemeh; Moinodin, Marzieh

    2007-12-01

    In this paper, a new method for quantification of rigidity in elbow joint of Parkinsonian patients is introduced. One of the most known syndromes in Parkinson's disease (PD) is increased passive stiffness in muscles, which leads to rigidity in joints. Clinical evaluation of stiffness in wrist and/or elbow, commonly used by clinicians, is based on Unified Parkinson's Disease Rating System (UPDRS). Subjective nature of this method may influence the accuracy and precision of evaluations. Hence, introducing an objective standard method based on quantitative measurements may be helpful. A test rig was designed and fabricated to measure range of motion and viscous and elastic components of passive stiffness in elbow joint. Measurements were done for 41 patients and 11 controls. Measures were extracted using Matlab-R14 software and statistic analyses were done by Spss-13. Relation between each computed measure and the level of illness were analyzed. Results showed a better correlation between viscous component of stiffness and UPDRS score compared to the elastic component. Results of this research may help to introduce a standard objective method for evaluation of PD. PMID:17909970

  16. [Neuropsychiatric non motor symptoms of Parkinson's disease].

    PubMed

    Peralta, Cecilia

    2012-01-01

    In the last decade we have witnessed substantial progress towards the understanding of Parkinson's disease. According to pathological and neuroimaging studies, the traditional view of Parkinson's disease that begins with the development of motor symptoms such as bradykinesia, rigidity and tremor, has begun to change. It is now understood that there would be a "premotor" or "preclinical" period in which the alphasynuclein pathology begins outside of the substantia nigra in the lower brainstem and autonomic nervous system. Although the pathophysiology of this phase is still unclear, it is currently thought that its symptoms would correspond to the so-called "non-motor symptoms". Hyposmia, depression, constipation and REM sleep disorders are one of the most relevant non-motor symptoms at this "premotor" stage. The spectrum of non-motor symptoms is very broad and covers the domains of neuropsychiatric, dysautonomic, gastrointestinal and sensory symptoms as well as sleep disorders. Neuropsychiatric symptoms such as depression, impulse control disorder, psychosis and dementia, are a major cause of disability as they are directly related to quality of life. PMID:23979552

  17. Autophonic loudness perception in Parkinson's disease.

    PubMed

    Brajot, François-Xavier; Shiller, Douglas M; Gracco, Vincent L

    2016-03-01

    The relationship between the intensity and loudness of self-generated (autophonic) speech remains invariant despite changes in auditory feedback, indicating that non-auditory processes contribute to this form of perception. The aim of the current study was to determine if the speech perception deficit associated with Parkinson's disease may be linked to deficits in such processes. Loudness magnitude estimates were obtained from parkinsonian and non-parkinsonian subjects across four separate conditions: self-produced speech under normal, perturbed, and masked auditory feedback, as well as auditory presentation of pre-recorded speech (passive listening). Slopes and intercepts of loudness curves were compared across groups and conditions. A significant difference in slope was found between autophonic and passive-listening conditions for both groups. Unlike control subjects, parkinsonian subjects' magnitude estimates under auditory masking increased in variability and did not show as strong a shift in intercept values. These results suggest that individuals with Parkinson's disease rely on auditory feedback to compensate for underlying deficits in sensorimotor integration important in establishing and regulating autophonic loudness. PMID:27036273

  18. Early-onset Parkinson's disease and depression.

    PubMed

    Bertucci Filho, Délcio; Teive, Hélio A G; Werneck, Lineu C

    2007-03-01

    Patients with Parkinsons disease (PD) in whom symptoms start before the age of 45 years (EOPD) present different clinical characteristics from those with the late-onset form of the disease. The incidence of depression is believed to be greater in patients with EOPD than with the late-onset form of the disease, although there is no risk factor or marker for depression in patients with PD. We studied 45 patients with EOPD to define the frequency of depression and to identify possible differences between the groups with and without depression. Depression was diagnosed in 16 (35.5%) of the patients, a higher incidence than in the population at large but similar to the figure for late-onset Parkinson disease; 8 (50%) of the patients had mild depression, 4 (25%) moderate depression and 4 (25%) were in remission. There was no relationship between depression and any of the clinical characteristics of the disease, although the EOPD patients with depression presented earlier levodopa-related complications and were more affected on the Hoehn-Yahr, UPDRS and Schwab-England scales. PMID:17420818

  19. Cognitive dysfunction and dementia in Parkinson disease.

    PubMed

    Caballol, Nuria; Martí, Maria J; Tolosa, Eduardo

    2007-09-01

    Impairment in different cognitive domains such as executive functions, language, memory, and visuospatial skills occurs frequently in Parkinson disease (PD) even in the early stages of the disease. Although frank dementia (Parkinson disease dementia, PDD) is less frequent, risk for developing dementia is two to six times greater than the prevalence rate in general population and it increases in relation to disease duration. Clinically, dementia in PD is characterized by uninsidious onset and slowly progressive cognitive decline, with a predominant dysexecutive syndrome accompanied frequently by a variety of behavioral symptoms such as hallucinations, depression, anxiety, and excessive daytime sleepiness. Although the exact pathophysiology and neurobiological basis of PDD is not known, dementia in PD probably develops as a result of progressive involvement of subcortical and cortical structures by Lewy-type pathology and associated Alzheimer-like histological changes. Dysfunction of different monoamine transmitter has also been implicated in the cognitive deterioration of PD but reduced cholinergic activity in the cortex is thought to account for the strongest mechanism in the development of dementia. Recent evidence suggests that cholinesterase inhibitors are effective in the treatment of dementia and accompanying behavioral symptoms in PD. PMID:18175397

  20. Detection of preclinical Parkinson's disease with PET

    SciTech Connect

    Brooks, D.J. )

    1991-08-01

    Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology.

  1. Detection of preclinical Parkinson's disease with PET

    SciTech Connect

    Brooks, D.J. )

    1991-05-01

    Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology.

  2. Active music therapy and Parkinson's disease: methods.

    PubMed

    Pacchetti, C; Aglieri, R; Mancini, F; Martignoni, E; Nappi, G

    1998-01-01

    Music therapy (MT) is an unconventional, multisensorial therapy poorly assessed in medical care but widely used to different ends in a variety of settings. MT has two branches: active and passive. In active MT the utilisation of instruments is structured to correspond to all sensory organs so as to obtain suitable motor and emotional responses. We conducted a prospective study to evaluate the effects of MT in the neurorehabilitation of patients with Parkinson's Disease (PD), a common degenerative disorder involving movement and emotional impairment. Sixteen PD patients took part in 13 weekly sessions of MT each lasting 2 hours. At the beginning and at the end of the session, every 2 weeks, the patients were evaluated by a neurologist, who assessed PD severity with UPDRS, emotional functions with Happiness Measures (HM) and quality of life using the Parkinson's Disease Quality of Life Questionnaire (PDQL). After every session a significant improvement in motor function, particularly in relation to hypokinesia, was observed both in the overall and in the pre-post session evaluations. HM, UPDRS-ADL and PDQL changes confirmed an improving effect of MT on emotional functions, activities of daily living and quality of life. In conclusion, active MT, operating at a multisensorial level, stimulates motor, affective and behavioural functions. Finally, we propose active MT as new method to include in PD rehabilitation programmes. This article describes the methods adopted during MT sessions with PD patients. PMID:9584875

  3. Taste in dementing diseases and parkinsonism.

    PubMed

    Lang, C J G; Leuschner, T; Ulrich, K; Stössel, C; Heckmann, J G; Hummel, T

    2006-10-25

    Like with many sensory abilities a reduction of taste and smell occurs during aging. Since there are hints to an additional reduction in dementing diseases, we assessed 52 patients, 26 women and 26 men, who were presented to a memory clinic, using the Sniffin' Sticks, Whole Mouth and Taste Strip Tests. While smoking, alcohol consumption, intake of drugs and sex exerted only minor impact, age and the severity of cognitive impairment were of major importance. There was a moderate but significant correlation between the severity of dementia, taste and smell, even if the age effect was partialled out. Notably, patients with Parkinson syndrome showed worse taste and smell abilities than those without. Here the differences were indeed marked enough to play a possible role in making the diagnosis. This exploratory study confirms a mild reduction of gustatory function in dementing diseases over and beyond that of normal aging which--in addition to a reduction of smell--seems to be especially marked in Parkinson syndromes. PMID:16769086

  4. Usefulness of pallidotomy in advanced Parkinson's disease.

    PubMed Central

    Johansson, F; Malm, J; Nordh, E; Hariz, M

    1997-01-01

    OBJECTIVE: The combined effect of posteroventral pallidotomy and optimal medical treatment was assessed in 22 patients with levodopa sensitive Parkinson's disease. METHODS: Timed motor tests, video recordings, and computer assisted optoelectronic movement analysis were used for serial hourly assessments performed preoperatively and four and 12 months after operation. Tests were made while patients were on optimal medical therapy. RESULTS: There were no serious adverse events of surgery. Two of the 22 patients could not complete all the tests after operation. The proportion of dyskinesia periods decreased in the 20 patients and there was a proportional increase in normal or fairly normal occasions. "Off" periods were not significantly affected. In 12 of 13 patients with limb dyskinesia this symptom was completely abolished in the contralateral limbs. There was also some degree of improvement axially and ipsilaterally. Tremor was moderately improved contralaterally. Bradykinesia remained unchanged. Results at 12 months follow up were similar to those at four months. CONCLUSION: Pallidotomy produced a pronounced positive effect on dyskinesia and a moderate effect on tremor. Bradykinesia was not affected. Posteroventral pallidotomy may be useful in patients with Parkinson's disease who have severe motor fluctuations and may allow an increase in levodopa dose to alleviate bradykinesia in "off" states. Images PMID:9048711

  5. Parkinson's Disease: The Mitochondria-Iron Link

    PubMed Central

    Carrasco, Carlos M.; Núñez, Marco T.

    2016-01-01

    Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson's disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1), a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage. These three occurrences—mitochondrial dysfunction, iron accumulation, and oxidative damage—generate a positive feedback loop of increased iron accumulation and oxidative stress. Here, we review the evidence that points to a link between mitochondrial dysfunction and iron accumulation as early events in the development of sporadic and genetic cases of Parkinson's disease. Finally, an attempt is done to contextualize the possible relationship between mitochondria dysfunction and iron dyshomeostasis. Based on published evidence, we propose that iron chelation—by decreasing iron-associated oxidative damage and by inducing cell survival and cell-rescue pathways—is a viable therapy for retarding this cycle. PMID:27293957

  6. Parkinson's disease--the continuing search for biomarkers.

    PubMed

    Breen, David P; Michell, Andrew W; Barker, Roger A

    2011-03-01

    There is currently no well-established biomarker for Parkinson's disease. The need to better diagnose the condition, define the subtypes of disease, and follow its course independent of any symptomatic drug effects is well-established. In this review, we will begin by reviewing the evidence for biological fluid biomarkers in Parkinson's disease. We will then touch upon the role of brain imaging in diagnosis and defining prognosis, as well as the value of studying motor phenotype and its potential applications for characterising Parkinson's disease subtypes with differing natural histories. PMID:21288170

  7. Anchanling reduces pathology in a lactacystin- induced Parkinson's disease model☆

    PubMed Central

    Li, Yinghong; Wu, Zhengzhi; Gao, Xiaowei; Zhu, Qingwei; Jin, Yu; Wu, Anmin; Huang, Andrew C. J.

    2012-01-01

    A rat model of Parkinson's disease was induced by injecting lactacystin stereotaxically into the left mesencephalic ventral tegmental area and substantia nigra pars compacta. After rats were intragastrically perfused with Anchanling, a Chinese medicine, mainly composed of magnolol, for 5 weeks, when compared with Parkinson's disease model rats, tyrosine hydroxylase expression was increased, α-synuclein and ubiquitin expression was decreased, substantia nigra cell apoptosis was reduced, and apomorphine-induced rotational behavior was improved. Results suggested that Anchanling can ameliorate Parkinson's disease pathology possibly by enhancing degradation activity of the ubiquitin-proteasome system. PMID:25767493

  8. The Parkinson Disease Mitochondrial Hypothesis: Where Are We at?

    PubMed

    Franco-Iborra, Sandra; Vila, Miquel; Perier, Celine

    2016-06-01

    Parkinson's disease is a common, adult-onset neurodegenerative disorder whose pathogenesis is still under intense investigation. Substantial evidence from postmortem human brain tissue, genetic- and toxin-induced animal and cellular models indicates that mitochondrial dysfunction plays a central role in the pathophysiology of the disease. This review discusses our current understanding of Parkinson's disease-related mitochondrial dysfunction, including bioenergetic defects, mitochondrial DNA alterations, altered mitochondrial dynamics, activation of mitochondrial-dependent programmed cell death, and perturbations in mitochondrial tethering to the endoplasmic reticulum. Whether a primary or secondary event, mitochondrial dysfunction holds promise as a potential therapeutic target to halt the progression of neurodegeneration in Parkinson's disease. PMID:25761946

  9. Parkinsonism and transient bilateral ptosis in systemic lupus erythematosus

    PubMed Central

    Teoh, P. C.; Richard, A. T. Ng; Wong, P. K.

    1974-01-01

    Many neurological abnormalities have been described in systemic lupus erythematosus (SLE), but transient bilateral ptosis and parkinsonism are rarely encountered. This paper describes a young Malay girl with SLE who develops psychosis, bilateral ptosis and parkinsonism during an exacerbation of her illness. These neurological features disappeared after adequate treatment with cyclophosphamide. Though the pathogenesis of these neurological abnormalities is not clearly known, it is likely that transient bilateral ptosis is due to myoneural dysfunction not unlike that of myasthenia gravis. As for parkinsonism, it can probably be explained on the basis of ‘vasculitis’ of the basal ganglia leading to microinfarcts and encephalomalacia. ImagesFig. 1Fig. 2

  10. Magnetic resonance parkinsonism index in progressive supranuclear palsy and vascular parkinsonism.

    PubMed

    Mostile, Giovanni; Nicoletti, Alessandra; Cicero, Calogero Edoardo; Cavallaro, Tiziana; Bruno, Elisa; Dibilio, Valeria; Luca, Antonina; Sciacca, Giorgia; Raciti, Loredana; Contrafatto, Donatella; Chiaramonte, Ignazio; Zappia, Mario

    2016-04-01

    To investigate accuracy of the magnetic resonance parkinsonism index (MRPI) in differentiating progressive supranuclear palsy (PSP) from vascular parkinsonism (VP). We retrospectively analyzed radiological data of 12 PSP patients and 17 VP patients group-matched by age and sex who performed a standardized brain magnetic resonance imaging (MRI). Analysis of selected structures morphometry was performed to all study subjects and the MRPI was calculated for each selected patient. MRI midbrain area as well as superior cerebellar peduncle width were significantly lower in PSP patients compared to VP subjects. MRPI was significantly larger in PSP patients compared to VP subjects. MRPI value ≥13 distinguished the two groups with a sensitivity of 100 % (95 % CI 69.9-100) and a specificity of 100 % (95 % CI 77.1-100). MRPI may represent an accurate tool in differentiating PSP from VP. PMID:26820655

  11. Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

    SciTech Connect

    Poduslo, S.E.; Schwankhaus, J.D.

    1994-09-01

    A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal, and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.

  12. Postural & striatal deformities in Parkinson`s disease: Are these rare?

    PubMed

    Pandey, Sanjay; Garg, Hitesh

    2016-01-01

    Parkinson`s disease (PD) is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS) and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD. PMID:26997007

  13. Frozen shoulder and other shoulder disturbances in Parkinson's disease.

    PubMed

    Riley, D; Lang, A E; Blair, R D; Birnbaum, A; Reid, B

    1989-01-01

    The frequency of shoulder disturbances, particularly frozen shoulder, has not been assessed previously in Parkinson's disease. In a survey of 150 patients compared with 60 matched control subjects a significantly higher incidence of both a history of shoulder complaints (43% vs. 23%) and frozen shoulder (12.7% vs. 1.7%) was found in the Parkinson's disease population. Those developing a frozen shoulder had initial disease symptoms indicative of akinesia twice as frequently as tremor while the ratio was reversed in those without frozen shoulder. In at least 8% of the patients frozen shoulder was the first symptom of disease, occurring 0-2 years prior to the onset of more commonly recognised features. Parkinson's disease should be added to the list of causes of frozen shoulder, and clinicians must be aware that the latter is often the presenting symptom of Parkinson's disease. PMID:2709037

  14. Study Links Severe Head Injury to Parkinson's Risk

    MedlinePlus

    ... News) -- A traumatic brain injury with loss of consciousness may increase the risk of developing Parkinson's disease, ... 865 had suffered a head injury and lost consciousness at some point in their lives -- some fairly ...

  15. Rivastigmine: new indication. Dementia and Parkinson's disease: no thank you!

    PubMed

    2007-04-01

    In patients with both Parkinson's disease and dementia, a placebo-controlled trial has confirmed that the adverse effects of rivastigmine outweigh its benefits. It is better to carefully adjust ongoing antiparkinsonian treatments than to add an anticholinesterase. PMID:17458048

  16. Understanding Parkinson Disease: A Complex and Multifaceted Illness.

    PubMed

    Gopalakrishna, Apoorva; Alexander, Sheila A

    2015-12-01

    Parkinson disease is an incredibly complex and multifaceted illness affecting millions of people in the United States. Parkinson disease is characterized by progressive dopaminergic neuronal dysfunction and loss, leading to debilitating motor, cognitive, and behavioral symptoms. Parkinson disease is an enigmatic illness that is still extensively researched today to search for a better understanding of the disease, develop therapeutic interventions to halt or slow progression of the disease, and optimize patient outcomes. This article aims to examine in detail the normal function of the basal ganglia and dopaminergic neurons in the central nervous system, the etiology and pathophysiology of Parkinson disease, related signs and symptoms, current treatment, and finally, the profound impact of understanding the disease on nursing care. PMID:26528949

  17. The history of parkinsonism: descriptions in ancient Indian medical literature.

    PubMed

    Ovallath, Sujith; Deepa, P

    2013-05-01

    The clinical syndrome of parkinsonism was identified in ancient India even before the period of Christ and was treated methodically. The earliest reference to bradykinesia dates to 600 bc. Evidences prove that as early as 300 bc, Charaka proposed a coherent picture of parkinsonism by describing tremor, rigidity, bradykinesia, and gait disturbances as its components. The scenario was further developed by Madhava, Vagbhata, and Dalhana all through history. The 15th-century classic "Bhasava rajyam" introduced the term kampavata, which may be regarded as an ayurvedic analogue of parkinsonism. The pathogenesis of kampavata centered on the concept of imbalance in the vata factor, which controls psychomotor activities. The essential element in therapy was the administration of powdered seed of Mucuna pruriens, or atmagupta, which as per reports, contains 4%-6% of levodopa. In addition to proving the existence and identification of parkinsonism in ancient India, the study points to the significance of ancient Indian Sanskrit works in medical history. PMID:23483637

  18. Recognition and management of neuropsychiatric complications in Parkinson's disease

    PubMed Central

    Ferreri, Florian; Agbokou, Catherine; Gauthier, Serge

    2006-01-01

    Parkinson's disease is primarily considered a motor disease characterized by rest tremor, rigidity, bradykinesia and postural disturbances. However, neuropsychiatric complications, including mood and anxiety disorders, fatigue, apathy, psychosis, cognitive impairment, dementia, sleep disorders and addictions, frequently complicate the course of the illness. The pathophysiologic features of these complications are multifaceted and include neuropathophysiologic changes of a degenerative disease, exposure to antiparkinsonian treatments and emotional reactions to having a disabling chronic illness. Changes in mental status have profound implications for the well-being of patients with Parkinson's disease and of their caregivers. Treatment is often efficacious but becomes a challenge in advanced stages of Parkinson's disease. In this article, we review the key clinical features of neuropsychiatric complications in Parkinson's disease as well as what is known about their epidemiologic characteristics, risk factors, pathophysiologic features and management. PMID:17146092

  19. Salivary Gland Biopsy Shows Promise to Helping to Diagnose Parkinson's

    MedlinePlus

    ... Parkinson's HelpLine Learn More Science News Salivary Gland Biopsy Shows Promise to Helping to Diagnose Parkinson’s - Mar ... team performed a procedure called a needle core biopsy of the submandibular glands in 15 people who ...

  20. Ipsilateral coordination features for automatic classification of Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Sarmiento, Fernanda; Atehortúa, Angélica; Martínez, Fabio; Romero, Eduardo

    2015-12-01

    A reliable diagnosis of the Parkinson Disease lies on the objective evaluation of different motor sub-systems. Discovering specific motor patterns associated to the disease is fundamental for the development of unbiased assessments that facilitate the disease characterization, independently of the particular examiner. This paper proposes a new objective screening of patients with Parkinson, an approach that optimally combines ipsilateral global descriptors. These ipsilateral gait features are simple upper-lower limb relationships in frequency and relative phase spaces. These low level characteristics feed a simple SVM classifier with a polynomial kernel function. The strategy was assessed in a binary classification task, normal against Parkinson, under a leave-one-out scheme in a population of 16 Parkinson patients and 7 healthy control subjects. Results showed an accuracy of 94;6% using relative phase spaces and 82;1% with simple frequency relations.

  1. Excessive daytime sleepiness in patients with Parkinson's disease.

    PubMed

    Knie, Bettina; Mitra, M Tanya; Logishetty, Kartik; Chaudhuri, K Ray

    2011-03-01

    Excessive daytime sleepiness (EDS) is described as inappropriate and undesirable sleepiness during waking hours and is a common non-motor symptom in Parkinson's disease, affecting up to 50% of patients. EDS has a large impact on the quality of life of Parkinson's disease patients as well as of their caregivers, in some cases even more than the motor symptoms of the disease. Drug-induced EDS is a particular problem as many dopamine agonists used for the treatment of Parkinson's disease have EDS as an adverse effect. Dopaminergic treatment may also render a subset of Parkinson's disease patients at risk for sudden-onset sleep attacks that occur without warning and can be particularly hazardous if the patient is driving. This demonstrates the need for early recognition and management not only to increase health-related quality of life but also to ensure patient safety. There are many assessment tools for EDS, including the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT), although only the Parkinson's Disease Sleep Scale (PDSS) and the SCales for Outcomes in PArkinson's Disease-Sleep (SCOPA-S) are specifically validated for Parkinson's disease. Polysomnography can be used when necessary. Management comprises non-pharmacological and pharmacological approaches. Non-pharmacological approaches can be the mainstay of treatment for mild to moderate EDS. Advice on good sleep hygiene is instrumental, as pharmacological approaches have yet to provide consistent and reliable results without significant adverse effects. The efficacy of pharmacological treatment of EDS in Parkinson's disease using wakefulness-promoting drugs such as modafinil remains controversial. Further areas of research are now also focusing on adenosine A(2A) receptor antagonists, sodium oxybate and caffeine to promote wakefulness. A definitive treatment for the highly prevalent drug-induced EDS has not yet been found. PMID:21323392

  2. Movement-related cortical activation in familial Parkinson disease.

    PubMed

    Delval, A; Defebvre, L; Labyt, E; Douay, X; Bourriez, J-L; Waucquiez, N; Derambure, P; Destée, A

    2006-09-26

    We sought to determine whether or not first-degree relatives of patients with familial Parkinson disease (FDRs) present impaired movement-related cortical activity. We studied 10 familial Parkinson disease subjects, 10 FDRs, and 10 controls and analyzed event-related mu desynchronization (ERD) and beta synchronization. Forty percent FDRs presented reduced premovement mu ERD latency, suggesting that premovement cortical activation is impaired in FDRs. PMID:17000986

  3. Why psychosis is frequently associated with Parkinson's disease?

    PubMed Central

    Zhong, Jingmei; Wu, Shaoyuan; Zhao, Ying; Chen, Hui; Zhao, Naiwei; Zheng, Kunwen; Zhao, Zhong; Chen, Wenli; Wang, Bo; Wu, Kunhua

    2013-01-01

    Psychosis is a common non-motor symptom of Parkinson's disease whose pathogenesis remains poorly understood. Parkinson's disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as well as within some cortical areas. In this study, Parkinson's disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson's disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pallidus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pallidus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson's disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pallidus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson's disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms (frontal lobe, occipital lobe, cingulate gyrus, and hippocampus) and those associated with the motor symptoms of Parkinson's disease (the substantia nigra and globus pallidus). The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why chosis often occurs in Parkinson's disease patients. PMID:25206565

  4. Parkin gene causing benign autosomal recessive juvenile parkinsonism.

    PubMed

    Nisipeanu, P; Inzelberg, R; Abo Mouch, S; Carasso, R L; Blumen, S C; Zhang, J; Matsumine, H; Hattori, N; Mizuno, Y

    2001-06-12

    Autosomal recessive juvenile parkinsonism (AR-JP) is an early-onset parkinsonism caused by exonic deletions or point mutations in the parkingene. The relationship between the type of the genetic defect and the clinical presentation, the response to therapy, and the evolution have not been yet determined. The authors describe a single-basepair deletion at nucleotide 202 in exon 2 of the parkin gene in a kindred with a benign clinical course. PMID:11402119

  5. Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

    PubMed Central

    Arnulf, Isabelle; Neutel, Dulce; Herlin, Bastien; Golmard, Jean-Louis; Leu-Semenescu, Smaranda; Cochen de Cock, Valérie; Vidailhet, Marie

    2015-01-01

    Objective: To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. Methods: The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. Results: The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P < 0.0001). They reached the levels of 114 patients with Parkinson disease (ESS: 8.7 ± 4.8), whether they had (n = 78) or did not have (n = 36) concomitant RBD. The severity of sleepiness in idiopathic RBD correlated with younger age, but not with sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1–15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). Conclusions: Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems. Citation: Arnulf I, Neutel D, Herlin B, Golmard JL, Leu-Semenescu S, Cochen de Cock V, Vidailhet M. Sleepiness in idiopathic REM sleep behavior disorder and Parkinson disease. SLEEP 2015;38(10):1529–1535. PMID:26085299

  6. Visual hallucinations in photographs in Parkinson's disease.

    PubMed

    Vaou, Okeanis; Saint-Hilaire, Marie; Friedman, Joseph

    2013-01-01

    Visual hallucinations are reported in 16-37% of drug-treated patients with Parkinson's disease (PD) and are the most common hallucinations in PD. We report two patients with PD with symptoms that uniquely integrate visual hallucinations and delusions. We report two cases of patients with PD with visual hallucinations who saw the persistence of these hallucinations in photographs. These pictures were taken to prove the absence of these hallucinations. We believe this is the first description of this peculiar phenomenon, in which hallucinations or illusions could be replicated in photographs. Both patients had delusions associated with the images and we speculate that the images they saw in the photographs represent a further delusion, hence a 'delusional hallucination' or 'delusional illusion.' We believe that delusions fostering hallucinations are rare. PMID:23704424

  7. Citicoline in the treatment of Parkinson's disease.

    PubMed

    Martí Massó, J F; Urtasun, M

    1991-01-01

    The subjects were 20 patients with Parkinson's disease. They were aged 52 to 76 years and the duration of the disease ranged from four to 25 years (mean, 12.5 years). All the patients were receiving levodopa alone or in combination with tricyclic antidepressants, amantadine, bromocriptine, anticholinergic agents, or lisuride. Each patient received 1,000 mg of citicoline intramuscularly daily for 15 days and then 500 mg daily for 15 days. After 30 days of treatment, the scores on the Columbia rating scale improved 7.3%; rigidity was improved 18.8%; times to walk 10 m and turn over were reduced 17.5% and 37.4%; and the handwriting test scores improved 19.7%. No side effects were reported. Four patients with advanced parkinsonian symptoms and psychotic side effects received 2,000 mg of citicoline subcutaneously or intravenously for seven days. No improvements in symptoms or treatment side effects were noted. PMID:1863939

  8. Primary dystonia misinterpreted as Parkinson disease

    PubMed Central

    Neuwelt, Alexander J.; Nguyen, Tam; Leehey, Maureen

    2013-01-01

    Summary Diagnosing dystonia can be challenging and depends on the recognition of subtle clinical signs. Due to clinical heterogeneity, variable age at presentation, and overlapping features with other disorders, dystonia is under-recognized. The presence of dystonic tremor is often a reason for misdiagnosis. We report an illustrative case of a patient with DYT1 dystonia who was originally misdiagnosed with Parkinson disease. Careful physical examination and history-taking can reveal dystonia and prompt appropriate diagnostic studies, which, in turn, can lead to potentially life-changing treatment. Our report illustrates typical challenges in the recognition and diagnosis of dystonia, and serves to increase clinicians' awareness of this disabling, but treatable, condition. PMID:24353921

  9. Cell therapy for Parkinson's disease: what next?

    PubMed

    Bjorklund, Anders; Kordower, Jeffrey H

    2013-01-01

    The idea to use transplants of dopamine-producing cells to substitute for the lost midbrain dopamine neurons in Parkinson's disease (PD) goes back to the 1970s. In this review we give an overview of the history of cell transplantation in animal models of PD, and summarize the experience gained from the open-label and placebo-controlled clinical trials performed so far using intrastriatal transplants of human fetal dopamine neuroblasts. Further development of this therapeutic approach face numerous challenges, for example in the development of protocols that allow generation of fully functional and safe midbrain dopamine neurons from stem cells. Based on recent promising advancements, efforts are now being made to develop standardized and efficient protocols, and adapt these protocols to good laboratory practice (GLP)/good manufacturing practice (GMP) conditions, to move this technology closer to clinical translation. PMID:23390097

  10. Nrf2: a modulator of Parkinson's disease?

    PubMed

    Todorovic, Michael; Wood, Stephen A; Mellick, George D

    2016-06-01

    Parkinson's disease (PD) is a complex multifactorial disorder that has been associated with the processes of oxidative stress. In the absence of curative therapies, modification of the neurodegenerative process-including the manipulation of endogenous antioxidant pathways-is the focus of intensive research. Recently, genetic and pharmacological accretion of the transcription factor, and phase II antioxidant 'master regulator' Nrf2, has shown to demonstrably mitigate the toxic neuronal effects of parkinsonian agents such as MPP(+), rotenone, and hydrogen peroxide in vitro and in vivo. Furthermore, baseline genetic variability in Nrf2-dependant pathways may promote neuronal susceptibility to exogenous agents and correlate with PD onset within certain populations. While contemporary evidence directly implicating Nrf2 in the pathogenesis of PD is not conclusive and likely contingent upon the evaluation of complex interacting factors-including genetic variation and a history of environmental exposures-it remains a promising target for therapeutic benefit in the modulation of oxidative stress. PMID:27145762

  11. [Insufficient medication compliance in Parkinson's disease].

    PubMed

    Aerts, Marjolein B; van der Eijk, Martijn; Kramers, Kees; Bloem, Bastiaan R

    2011-01-01

    Medication compliance is generally suboptimal, particularly in patients with complex polypharmacy. This generic treatment problem is described here for Parkinson's disease (PD). We would expect patients with PD to have good medication compliance, since missed doses immediately result in worsening of symptoms. However, recent research has revealed that PD patients demonstrate poor medication compliance. Poor medication compliance is particularly undesirable for patients with PD because regular intake of medication is required for optimal treatment effect. Possible ways of improving medication compliance are pharmacotherapeutic measures and behavioural interventions. Modern methods of communication (text message reminders) and 'smart' pill dispensers may be beneficial, but the advantages of such interventions have not yet been scientifically studied. PMID:21527053

  12. Cognitive-motor learning in Parkinson's disease.

    PubMed

    Haaland, K Y; Harrington, D L; O'Brien, S; Hermanowicz, N

    1997-04-01

    Procedural learning deficits are common in Parkinson's disease (PD), but contradictory results have been reported in rotary pursuit learning. This article compared rotary pursuit learning in 2 nondemented PD groups and 2 normal control (NC) groups, using a between-subjects group design in which 3 rotation speeds were presented either randomly or in blocks. The pattern of learning differed between the randomized and the blocked conditions in the NC, but not in the PD groups. Learning was impaired in the PD group in the random condition only. Memory, visuospatial, or executive skills were not associated with the PD group's poorer learning in the randomized context. Results show that procedural learning deficits are not universal with basal ganglia abnormalities but rather depend on the specific cognitive requirements of the learning context. PMID:9110325

  13. Advances in Biomarker Research in Parkinson's Disease.

    PubMed

    Mehta, Shyamal H; Adler, Charles H

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future. PMID:26711276

  14. Parkinson's Disease and Sleep/Wake Disturbances

    PubMed Central

    Swick, Todd J.

    2012-01-01

    Parkinson's disease (PD) has traditionally been characterized by its cardinal motor symptoms of bradykinesia, rigidity, resting tremor, and postural instability. However, PD is increasingly being recognized as a multidimensional disease associated with myriad nonmotor symptoms including autonomic dysfunction, mood disorders, cognitive impairment, pain, gastrointestinal disturbance, impaired olfaction, psychosis, and sleep disorders. Sleep disturbances, which include sleep fragmentation, daytime somnolence, sleep-disordered breathing, restless legs syndrome (RLS), nightmares, and rapid eye movement (REM) sleep behavior disorder (RBD), are estimated to occur in 60% to 98% of patients with PD. For years nonmotor symptoms received little attention from clinicians and researchers, but now these symptoms are known to be significant predictors of morbidity in determining quality of life, costs of disease, and rates of institutionalization. A discussion of the clinical aspects, pathophysiology, evaluation techniques, and treatment options for the sleep disorders that are encountered with PD is presented. PMID:23326757

  15. Movement-related potentials in Parkinson's disease.

    PubMed

    Georgiev, Dejan; Lange, Florian; Seer, Caroline; Kopp, Bruno; Jahanshahi, Marjan

    2016-06-01

    To date, many different approaches have been used to study the impairment of motor function in Parkinson's disease (PD). Event-related potentials (ERPs) are averaged amplitude fluctuations of the ongoing EEG activity that are time locked to specific sensory, motor or cognitive events, and as such can be used to study different brain processes with an excellent temporal resolution. Movement-related potentials (MRPs) are ERPs associated with processes of voluntary movement preparation and execution in different paradigms. In this review we concentrate on MRPs in PD. We review studies recording the Bereitschaftspotential, the Contingent Negative Variation, and the lateralized readiness potential in PD to highlight the contributions they have made to further understanding motor deficits in PD. Possible directions for future research are also discussed. PMID:27178872

  16. Diagnosis and management of Parkinson's disease dementia

    PubMed Central

    Poewe, W; Gauthier, S; Aarsland, D; Leverenz, J B; Barone, P; Weintraub, D; Tolosa, E; Dubois, B

    2008-01-01

    Parkinson's disease (PD) has long been considered predominantly a motor disorder. However, its frequent association with dementia, which contributes significantly to the morbidity and mortality of the condition, is gaining increasing recognition. PD dementia (PDD) has a unique clinical profile and neuropathology, distinct from Alzheimer's disease (AD). Cholinergic deficits, a feature of both AD and PDD, underlie the rationale for cholinesterase inhibitor therapy in both conditions. In clinical practice, it is important that PDD should be recognised and appropriately treated. This review aims to outline the recently proposed clinical diagnostic criteria for PDD and to summarise the guidelines/recommendations published since 2006 on the use of cholinesterase inhibitors in the management of PDD. Although the cholinesterase inhibitor rivastigmine has recently been approved for the management of PDD, there remains a need for the development of novel therapies that can affect key mechanisms of the disease or prevent/delay patients with PD and mild cognitive impairment from progressing to PDD. PMID:18822028

  17. Tremor: Is Parkinson's disease a dynamical disease?

    NASA Astrophysics Data System (ADS)

    Beuter, Anne; Vasilakos, Konstantinon

    1995-03-01

    Experimental evidence has shown a plethora of short-term fluctuations in patients with Parkinson's disease. We investigate these transitory events using the concept of dynamical disease. Several examples of short-term fluctuations in tremor are analyzed, and in two cases, other systemic variables (i.e., respiration and blood pressure) are examined as well. A model for tremor, based on negative feedback with delays is proposed, and the transient events are simulated. The theoretical implications of the model suggest that interactions between the central and peripheral loops, as well as interactions between the control loops and other systemic signals, can give rise to transitory events in tremor, both in the pathological and in the normal case.

  18. Adaptive deep brain stimulation in Parkinson's disease.

    PubMed

    Beudel, M; Brown, P

    2016-01-01

    Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application. PMID:26411502

  19. A novel treatment target for Parkinson's disease.

    PubMed

    Wakade, Chandramohan; Chong, Raymond

    2014-12-15

    We hypothesize that GPR109A message and expression are up-regulated in individuals with Parkinson's disease (PD). GPR109A is a high-affinity niacin receptor. Niacin is a precursor for NAD-NADH which is needed for dopamine production. Thus, niacin supplementation may serve three purposes: reduce inflammation through GPR109A-related mechanisms, increase dopamine synthesis in the striatum through NADPH supply and increase NAD/NADH ratio to boost mitochondrial functions. GPR109A and its agonists are known to exert anti-inflammatory actions in the skin, gut and retina. However these roles are neither anticipated nor established in the CNS. For the first time here we propose the roles of GPR109A and its agonists including niacin in CNS pathology. Moreover we predict that the neuroprotective roles of either niacin or butyrates in CNS occur via GPR109A. PMID:25455298

  20. Impaired intracellular trafficking defines early Parkinson's disease

    PubMed Central

    Hunn, Benjamin H.M.; Cragg, Stephanie J.; Bolam, J. Paul; Spillantini, Maria-Grazia; Wade-Martins, Richard

    2015-01-01

    Parkinson's disease (PD) is an insidious and incurable neurodegenerative disease, and represents a significant cost to individuals, carers, and ageing societies. It is defined at post-mortem by the loss of dopamine neurons in the substantia nigra together with the presence of Lewy bodies and Lewy neurites. We examine here the role of α-synuclein and other cellular transport proteins implicated in PD and how their aberrant activity may be compounded by the unique anatomy of the dopaminergic neuron. This review uses multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells, and refined animal models to argue that prodromal PD can be defined as a disease of impaired intracellular trafficking. Dysfunction of the dopaminergic synapse heralds trafficking impairment. PMID:25639775

  1. Depression and disability in Parkinson's disease.

    PubMed

    Cole, S A; Woodard, J L; Juncos, J L; Kogos, J L; Youngstrom, E A; Watts, R L

    1996-01-01

    The relationship between depression and disability in idiopathic Parkinson's disease (PD) was examined in 31 outpatients. Thirteen percent had current major depression (MD), 10% dysthymia, and 32% a lifetime history of MD. Depression was significantly related to both illness severity and functional impairment. Male patients with early-onset PD (before age 55) had more mood and anxiety disorders than late-onset male patients. Patients with right-sided PD had significantly more depressive symptoms than those with left-sided PD. On multiple regression analyses, depression predicted impaired social, role, and physical functioning for men (but not for women), independent of the impact of illness severity. The results suggest that treatment of depression may improve function; however, findings of gender differences will require replication. PMID:8845697

  2. [The cognitive dysfunction in Parkinson's disease].

    PubMed

    Kanazawa, Akira

    2004-09-01

    Parkinson's disease (PD) is a slowly progressive disorder which begins with motor symptoms. Several cognitive deficits can be observed in nondemented patients with PD during their history. The core symptom in the cognitive deficits in PD is the executive dysfunction. Neuropsychological tests such as Wisconsin Card Sorting Test, Trail Making Test are used to measure the degree of this dysfunction. Executive dysfunction is thought related to abnormalities in the dorsolateral prefrontal circuit which largely passes through the caudate nucleus. The dysfunction emerges as the pathology spreads to the nigrocaudate project corresponding to Hoehn & Yahr stage II-III. Effective therapy for cognitive dysfunction in PD remains elusive, however donepezil, Attention Process Training, Music therapy and Transcranial magnetic stimulation have been reported to have partial efficacy. PMID:15462384

  3. Nonpharmacological treatments for patients with Parkinson's disease.

    PubMed

    Bloem, Bastiaan R; de Vries, Nienke M; Ebersbach, Georg

    2015-09-15

    Since 2013, a number of studies have enhanced the literature and have guided clinicians on viable treatment interventions outside of pharmacotherapy and surgery. Thirty-three randomized controlled trials and one large observational study on exercise and physiotherapy were published in this period. Four randomized controlled trials focused on dance interventions, eight on treatment of cognition and behavior, two on occupational therapy, and two on speech and language therapy (the latter two specifically addressed dysphagia). Three randomized controlled trials focused on multidisciplinary care models, one study on telemedicine, and four studies on alternative interventions, including music therapy and mindfulness. These studies attest to the marked interest in these therapeutic approaches and the increasing evidence base that places nonpharmacological treatments firmly within the integrated repertoire of treatment options in Parkinson's disease. PMID:26274930

  4. Parkinson patients as partners in care.

    PubMed

    Hirsch, Mark A; Sanjak, Mohammed; Englert, Danielle; Iyer, Sanjay; Quinlan, Margaret M

    2014-01-01

    Increasing physical activity, as part of an active lifestyle, is an important health goal for individuals with Parkinson's disease (PD). Exercise can positively impact health related quality of life. Given this, how can we promote physically active lifestyles among PD patients (most of whom are sedentary)? Here we suggest that health care professionals could significantly expand their impact by collaborating with PD patients and their spouses (or caregivers) as partners-in-care. We outline reasons why partners-in-care approaches are important in PD, including the need to increase social capital, which deals with issues of trust and the value of social networks in linking members of a community. We then present results of a qualitative study involving partners-in-care exercise beliefs among 19 PD patients and spouses, and conclude with our perspective on future benefits of this approach. PMID:24262175

  5. Peripheral neuropathy and parkinsonism: a large clinical and pathogenic spectrum.

    PubMed

    Vital, Anne; Lepreux, Sebastien; Vital, Claude

    2014-12-01

    Peripheral neuropathy (PN) has been reported in idiopathic and hereditary forms of parkinsonism, but the pathogenic mechanisms are unclear and likely heterogeneous. Levodopa-induced vitamin B12 deficiency has been discussed as a causal factor of PN in idiopathic Parkinson's disease, but peripheral nervous system involvement might also be a consequence of the underlying neurodegenerative process. Occurrence of PN with parkinsonism has been associated with a panel of mitochondrial cytopathies, more frequently related to a nuclear gene defect and mainly polymerase gamma (POLG1) gene. Parkin (PARK2) gene mutations are responsible for juvenile parkinsonism, and possible peripheral nervous system involvement has been reported. Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the β-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations. This article reviews conditions in which PN may coexist with parkinsonism. PMID:25582874

  6. Frontal deficits differentiate progressive supranuclear palsy from Parkinson's disease.

    PubMed

    Lee, Young-Eun C; Williams, David R; Anderson, Jacqueline F I

    2016-03-01

    The clinical differentiation of progressive supranuclear palsy from Parkinson's disease can be challenging, due to overlapping clinical features and a lack of diagnostic markers. Abnormalities in cognitive function form part of the clinical spectrums of these diseases and distinctive cognitive profiles may be helpful in differentiating these diseases in the diagnostic period. A comprehensive neuropsychological test battery was administered to 12 patients with clinically diagnosed progressive supranuclear palsy and 12 patients with Parkinson's disease matched for age and disease duration. Effect size (Cohen's d) was calculated for cognitive tests that were significantly different between groups. Patients with progressive supranuclear palsy performed significantly worse than those with Parkinson's disease on measures of processing speed, verbal fluency, planning, verbal abstract reasoning, verbal memory, and made more perseverative responses on a set shifting task. Measures of executive function, manual dexterity and processing speed were most diagnostically useful (Cohen's d > 2.0) in differentiating between progressive supranuclear palsy and Parkinson's disease. These findings suggest that more severe and prominent 'frontal' cognitive deficits in patients with progressive parkinsonism would be helpful in predicting progressive supranuclear palsy rather than Parkinson's disease and these findings may contribute to the development of diagnostic criteria. PMID:25223526

  7. Early Freezing of Gait: Atypical versus Typical Parkinson Disorders.

    PubMed

    Lieberman, Abraham; Deep, Aman; Dhall, Rohit; Tran, An; Liu, Ming-Jai

    2015-01-01

    In 18 months, 850 patients were referred to Muhammad Ali Parkinson Center (MAPC). Among them, 810 patients had typical Parkinson disease (PD) and 212 had PD for ≤5 years. Among the 212 patients with early PD, 27 (12.7%) had freezing of gait (FOG). Forty of the 850 had atypical parkinsonism. Among these 40 patients, all of whom had symptoms for ≤5 years, 12 (30.0%) had FOG. FOG improved with levodopa in 21/27 patients with typical PD but did not improve in the 12 patients with atypical parkinsonism. FOG was associated with falls in both groups of patients. We believe that FOG unresponsive to levodopa in typical PD resembles FOG in atypical parkinsonism. We thus compared the 6 typical PD patients with FOG unresponsive to levodopa plus the 12 patients with atypical parkinsonism with the 21 patients with typical PD responsive to levodopa. We compared them by tests of locomotion and postural stability. Among the patients with FOG unresponsive to levodopa, postural stability was more impaired than locomotion. This finding leads us to believe that, in these patients, postural stability, not locomotion, is the principal problem underlying FOG. PMID:25785228

  8. Biomarkers for dementia and mild cognitive impairment in Parkinson's disease.

    PubMed

    Delgado-Alvarado, Manuel; Gago, Belén; Navalpotro-Gomez, Irene; Jiménez-Urbieta, Haritz; Rodriguez-Oroz, María C

    2016-06-01

    Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well-established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin-like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society. PMID:27193487

  9. Morbidity in early Parkinson's disease and prior to diagnosis

    PubMed Central

    Frandsen, Rune; Kjellberg, Jakob; Ibsen, Rikke; Jennum, Poul

    2014-01-01

    Background Nonmotor symptoms are probably present prior to, early on, and following, a diagnosis of Parkinson's disease. Nonmotor symptoms may hold important information about the progression of Parkinson's disease. Objective To evaluated the total early and prediagnostic morbidities in the 3 years before a hospital contact leading to a diagnosis of Parkinson's disease. Methods Retrospective morbidity data from Danish National Patient Registry records (1997–2007) of 10,490 adult patients with a secondary care diagnosis of Parkinson's disease were compared with 42,505 control cases. Results Parkinson's disease was associated with significantly higher morbidity rates associated with conditions in the following categories: mental and psychiatric, nervous system, gastrointestinal, musculoskeletal system and connective tissue, genitourinary, abnormal clinical and laboratory findings, injury, poisoning and certain other external causes, and other factors influencing health status and contact with health services. It was negatively associated with neoplasm, cardiovascular, and respiratory diseases. Conclusions Patients with a diagnosis of Parkinson's disease present significant differences in morbidities early on, following, and prior to, their diagnosis, compared with healthy controls. PMID:24944873

  10. Hallucinations and psychosis in Parkinson's disease.

    PubMed

    Rabey, Josè Martin

    2009-12-01

    Although Parkinson's disease (PD) is considered mainly a movement disorder, robust information accumulated during the last 30 years has shown that about 30% of PD patients may also suffer from psychosis, which deeply affects their quality of life and eventually brings them to permanent hospitalization in nursing homes. PD psychosis (PDPsy) mainly occurs after 10 or more years of treatment. The main features of PDPsy include recurrent and continuous hallucinations and delusions for at least 1 month. In addition, a recent consensus of the National Institute of Neurological Disorders and Stroke and National Institute of Mental Health Working Group also included illusions and a false sense of presence as "minor symptoms" supporting the diagnosis. In addition, accumulated clinical data have shown that "minor symptoms" and benign hallucinations also imply a bad prognosis with time. In the diagnostic criteria for PDPsy, it is considered that patients suffer from PD for at least more than 1 year before psychosis develops. If this is not the case, there is an unsolved problem of an overlapping diagnosis with Dementia with Lewy Bodies. Most clinicians consider that the main cause of psychosis is chronic exposure to dopaminergic medication. However, from an operational point of view there remain difficulties in defining a specific time of exposure and dose of treatment and the occurrence of PDPsy. Specific rating scales have been developed for the evaluation of PDPsy, such as the Parkinson Psychosis Rating Scale. The Scale for the Assessment of Positive Symptoms usually applied in schizophrenic patients has also proved useful for scoring psychotic symptomatology in PD. Clozapine in low doses has been proven to be the most effective antipsychotic medication for PDPsy. However, its use may cause neutropenia. Therefore, new atypical antipsychotic drugs with serotonin 5-HT2A receptor inverse agonist properties have been developed. Recently, pimavanserin--a 5-HT2A inverse agonist

  11. Is acupuncture efficacious therapy in Parkinson's disease?

    PubMed

    Kim, Hee Jin; Jeon, Beom S

    2014-06-15

    This review aims to assess the evidences from recent clinical studies regarding the efficacy of acupuncture on Parkinson's disease. Relevant literatures were searched from 13 databases under the condition "published between 2000 and 2012" with language restrictions. Eleven studies were indentified including 6 randomized clinical trials (RCTs), 4 uncontrolled open label studies, and 1 crossover trial. The number of trials, and their total sample size were not enough to prove the favorable effects of acupuncture. Five studies failed to report proper diagnostic criteria for enrollment. Two of the 6 RCTs did not include the randomization methods and whether the assessors were blinded. Drop-outs were unreported or insufficiently reported in 2 trials. Three RCTs compared the effects of acupuncture with placebo acupuncture. Two of these trials failed to show superiority of acupuncture. One RCT showed beneficial effects of constitutional acupuncture, but not needle acupuncture. Three RCTs that assessed the effects of acupuncture adjunctive to conventional drugs reported beneficial effects of acupuncture. The placebo response to acupuncture was not excluded, because there was no control acupuncture group in these studies. Two uncontrolled studies showed significant positive effects of acupuncture, while other two uncontrolled trials failed. There were no recognized validated acupuncture treatment protocols and a lack of consensus on the location of acupoints. Safety and tolerability were reported only in 5 studies. No study evaluated the long-lasting effect of acupuncture following cessation of the treatment. To date, the evidence for the effectiveness of acupuncture for treating Parkinson's disease is not convincing. There are needs for further studies with improved methodological quality. PMID:24798223

  12. History of Wolff-Parkinson-White syndrome.

    PubMed

    Scheinman, Melvin M

    2005-02-01

    While Drs. Wolff, Parkinson, and White fully described the syndrome that bears their names in 1930, prior case reports had already described the essentials. Over the ensuing century this syndrome has captivated the interest of anatomists, clinical cardiologists, and cardiac surgeons. Stanley Kent described lateral muscular connections over the atrioventricular (AV) groove, which he felt were the normal AV connections. The normal AV connections were, however, clearly described by His and Tawara. True right-sided AV connections were initially described by Wood et al., while Ohnell first described left free wall pathways. David Scherf is thought to be the first to describe our current understanding of the pathogenesis of the Wolff-Parkinson-White (WPW) syndrome in terms of a reentrant circuit involving both the AV node--His axis as well as the accessory pathway. This hypothesis was not universally accepted and many theories were applied to explain the clinical findings. The basics of our understandings were established by the brilliant work of Pick, Langendorf, and Katz who by using careful deductive analysis of ECGs were able to define the basic pathophysiological processes. Subsequently, Wellens and Durrer applied invasive electrical stimulation to the heart in order to confirm the pathophysiological processes. Sealy and his colleagues at Duke University Medical Center were the first to successfully surgically divide an accessory pathway and ushered in the modern area for curative therapy for these patients. Morady and Scheinman were the first to successfully ablate an accessory pathway (posteroseptal) using high-energy direct-current shocks. Subsequently, Jackman, Kuck, Morady, and a number of groups proved the remarkable safety and efficiency of catheter ablation for pathways in all locations using radiofrequency energy. More recently, Gallob et al. first described the gene responsible for a familial form of WPW. The current ability to cure patients with WPW is

  13. [Pharmacotherapy of Parkinson's disease: progress or regress?].

    PubMed

    Pytka, Karolina; Zygmunt, Małgorzata; Filipek, Barbara

    2013-01-01

    Parkinson's disease (PD) is a chronic, progressive disease of the central nervous system (CNS), characterized by a slow loss of dopaminergic neurons in the substantia nigra, leading to significant decrease in dopamine (DA) levels in the striatum. Currently used drugs, such as levodopa (L-DOPA), amantadine, dopamine agonists (D) or anticholinergic drugs, are not effective enough, and do not eliminate the causes of disease. Many research centers are conducting research on new forms of currently used drugs (e.g. Duodopa, XP21279, IPX066), new drugs of already known groups (e.g. safinamide), medicines that suppress side effects of L-DOPA (e.g. AFQ056, fipamezole), and, finally, compounds with a novel mechanism of action (e.g. PMY50028, A2A receptor antagonists). A lot of scientific reports indicate an important role of A2A receptors in the regulation of the central movement system, so a new group of compounds - selective antagonists of A2A receptors (e.g. istradefylline, preladenant, SYN115) - has been developed and their potential use in PD has been examined. Clinical studies of A2A receptor antagonists have shown that this group of compounds can shorten off periods and at the same time they do not worsen dyskinesias in patients with PD. Moreover, there is ongoing research on new forms of treatment, such as gene therapy. Attempts to apply the viral vector AAV-2, which will be able to infect neurons with a variety of genes, including the gene of glutamate decarboxylase (GAD), neurturin (NTN), or aromatic L-amino acid decarboxylase, are currently being carried out. The results of phase I and II clinical studies showed some efficacy of this form of treatment, but the method requires further studies. An analysis of potential future therapies of Parkinson's disease suggests that some progress in this field has been made. PMID:24018435

  14. The cybrid model of sporadic Parkinson's disease.

    PubMed

    Trimmer, Patricia A; Bennett, James P

    2009-08-01

    Parkinson's disease (PD) is the eponym attached to the most prevalent neurodegenerative movement disorder of adults, derived from observations of an early nineteenth century physician and paleontologist, James Parkinson, and is now recognized to encompass much more than a movement disorder clinically or dopamine neuron death pathologically. Most PD ( approximately 90%) is sporadic (sPD), is associated with mitochondrial deficiencies and has been studied in cell and animal models arising from the use of mitochondrial toxins that unfortunately have not predicted clinical efficacy to slow disease progression in humans. We have extensively studied the cytoplasmic hybrid ("cybrid") model of sPD in which donor mtDNAs are introduced into and expressed in neural tumor cells with identical nuclear genetic and environmental backgrounds. sPD cybrids demonstrate many abnormalities in which increased oxidative stress drives downstream antioxidant response and cell death activating signaling pathways. sPD cybrids regulate mitochondrial ETC genes and gene ontology families like sPD brain. sPD cybrids spontaneously form Lewy bodies and Lewy neurites, linking mtDNA expression to neuropathology, and demonstrate impaired organelle transport in processes and reduced mitochondrial respiration. Our recent studies show that near-infrared laser light therapy normalizes mitochondrial movement and can stimulate respiration in sPD cybrid neurons, and mitochondrial gene therapy can restore respiration and stimulate mitochondrial ETC gene and protein expression. sPD cybrids have provided multiple lines of circumstantial evidence linking mtDNA to sPD pathogenesis and can serve as platforms for therapy development. sPD cybrid models can be improved by the use of non-tumor human stem cell-derived neural precursor cells and by an introduction of postmortem brain mtDNA to test its causality directly. PMID:19328199

  15. VPS35 Mutations in Parkinson Disease

    PubMed Central

    Vilariño-Güell, Carles; Wider, Christian; Ross, Owen A.; Dachsel, Justus C.; Kachergus, Jennifer M.; Lincoln, Sarah J.; Soto-Ortolaza, Alexandra I.; Cobb, Stephanie A.; Wilhoite, Greggory J.; Bacon, Justin A.; Behrouz, Bahareh; Melrose, Heather L.; Hentati, Emna; Puschmann, Andreas; Evans, Daniel M.; Conibear, Elizabeth; Wasserman, Wyeth W.; Aasly, Jan O.; Burkhard, Pierre R.; Djaldetti, Ruth; Ghika, Joseph; Hentati, Faycal; Krygowska-Wajs, Anna; Lynch, Tim; Melamed, Eldad; Rajput, Alex; Rajput, Ali H.; Solida, Alessandra; Wu, Ruey-Meei; Uitti, Ryan J.; Wszolek, Zbigniew K.; Vingerhoets, François; Farrer, Matthew J.

    2011-01-01

    The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD. PMID:21763482

  16. Living Well with Parkinson's Disease is an Art | NIH MedlinePlus the Magazine

    MedlinePlus

    ... about Parkinson's. Photo courtesy of Rob Cunningham When did you first get diagnosed with Parkinson's disease? What ... took up painting after you were diagnosed. How did you decide to do that? Does your condition ...

  17. Parkinson's Disease: New Research Offers Hope for Better Diagnosis and Treatments

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Parkinson's Disease New Research Offers Hope for Better Diagnosis and Treatments ... to rule out other diseases. Read More "Parkinson's Disease" Articles New Research Offers Hope for Better Diagnosis and Treatments / ...

  18. The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

    PubMed Central

    Goetz, Christopher G.

    2011-01-01

    Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease. PMID:22229124

  19. Antipsychotic Drugs Tied to Risk of Early Death in Parkinson's Patients

    MedlinePlus

    ... Drugs Tied to Risk of Early Death in Parkinson's Patients But it's unclear whether the medications or ... 22, 2016 (HealthDay News) -- New research suggests that Parkinson's patients who are given antipsychotics to treat dementia ...

  20. The history of Parkinson's disease: early clinical descriptions and neurological therapies.

    PubMed

    Goetz, Christopher G

    2011-09-01

    Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease. PMID:22229124

  1. People with Gaucher Disease at Seven to Nine Percent Risk of Developing Parkinson's

    MedlinePlus

    ... alike — in PDF's new scientific journal. Browse Now Parkinson's HelpLine Learn More Science News People with Gaucher ... at Seven to Nine Percent Risk of Developing Parkinson's - May 16 2014 Researchers have shown that people ...

  2. Parkinson's Disease: Diagnosis and Treatment | NIH MedlinePlus the Magazine

    MedlinePlus

    ... therapies for Parkinson's include massage, yoga, tai chi, hypnosis, acupuncture, and the Alexander technique, which optimizes posture ... therapies for Parkinson's include massage, yoga, tai chi, hypnosis, acupuncture, and the Alexander technique, which optimizes posture ...

  3. Imaging Amyloidopathy in Parkinson Disease and Parkinsonian Dementia Syndromes

    PubMed Central

    Frey, Kirk A.; Petrou, Myria

    2015-01-01

    Dementia arising in patients with Parkinson disease or parkinsonian neurodegeneration comprises a heterogeneous neuropathology. Clinical labeling of patients with both dementia and Parkinson disease is dichotomous, depending on the temporal development of cognitive impairment and motor parkinsonism. Patients with dementia arising first (or within the first year of PD) are classified as dementia with Lewy bodies; patients with PD for more than one year before cognitive decline are classified as Parkinson disease with dementia. Despite this differential clinical classification, autopsy studies demonstrate variable admixtures of cortical synuicleinopathy, Aβ-amyloidopathy and tau neurofibrillary tangle deposition. There are no routine clinical diagnostic measures that accurately distinguish the underlying neuropathologies in individual patients. In the present paper, we review the published literature describing characteristics of fibrillary Aβ-amyloid deposition on the basis of PET radiotracer imaging in patients with Parkinson disease and in parkinsonian dementia syndromes. Although individual reports often include only small-to-modest subject numbers, there is overall suggestion that PD patients have a lower incidence of Aβ-amyloid deposition than seen amongst elderly normal subjects, and that Parkinson disease with dementia patients have a lower incidence of Aβ-amyloid deposition than do patients with dementia with Lewy bodies. These apparent features contrast the findings of Aβ-amyloid-PET imaging in normal aging and the development of Alzheimer disease, where Aβ-amyloid deposition arises asymptomatically and apparently many years before development of signs or symptoms of dementia. It is proposed that focused, prospective studies are needed to further address and understand the complex role(s) of Aβ-amyloid pathology in Parkinson disease, and that this understanding will be critical to the development of targeted disease-modifying therapy for dementia in

  4. Is PIGD a legitimate motor subtype in Parkinson disease?

    PubMed

    Kotagal, Vikas

    2016-06-01

    Parkinson disease is a chronic progressive syndrome with a broad array of clinical features. Different investigators have suggested the heterogeneous motor manifestations of early Parkinson disease can be conceptualized through a taxonomy of clinical subtypes including tremor-predominant and postural instability and gait difficulty-predominant subtypes. Although it is theoretically valuable to distinguish subtypes of Parkinson disease, the reality is that few patients fit these discrete categories well and many transition from exhibiting elements of one subtype to elements of another. In the time since the initial description of the postural instability and gait difficulty-predominant subtype, Parkinson disease clinical research has blossomed in many ways - including an increased emphasis on the role of medical comorbidities and extranigral pathologies in Parkinson disease as markers of prognostic significance. By conceptualizing the pathogenesis of an expansive disease process in the limited terms of categorical motor subtypes, we run the risk of overlooking or misclassifying clinically significant pathogenic risk factors that lead to the development of motor milestones such as falls and related axial motor disability. Given its critical influence on quality of life and overall prognosis, we are in need of a model of postural instability and gait difficulty-predominant features in Parkinson disease that emphasizes the overlooked pathological influence of aging and medical comorbidities on the development of axial motor burden and postural instability and gait difficulty-predominant features. This Point of View proposes thinking of postural instability and gait difficulties in Parkinson disease not as a discrete subtype, but rather as multidimensional continuum influenced by several overlapping age-related pathologies. PMID:27547776

  5. Hearing impairment in Parkinson's disease: expanding the nonmotor phenotype.

    PubMed

    Vitale, Carmine; Marcelli, Vincenzo; Allocca, Roberto; Santangelo, Gabriella; Riccardi, Pasquale; Erro, Roberto; Amboni, Marianna; Pellecchia, Maria Teresa; Cozzolino, Autilia; Longo, Katia; Picillo, Marina; Moccia, Marcello; Agosti, Valeria; Sorrentino, G; Cavaliere, Michele; Marciano, Elio; Barone, Paolo

    2012-10-01

    The objective of this study was to evaluate hearing impairment in patients affected by Parkinson's disease compared with hearing scores observed in normal age- and sex-matched controls. One hundred eighteen consecutive patients with a clinical diagnosis of Parkinson's disease were screened. Severity of motor symptoms and staging were measured with the Unified Parkinson's Disease Rating Scale (section III) and the Hoehn and Yahr scale. Audiometric evaluation consisted of a comprehensive audiologic case history and questionnaire, visual otoscopic examination, acoustic immittance measures (tympanogram and acoustic reflexes), pure tone audiometry, and measurement of brain stem auditory-evoked potentials. Healthy age- and sex-matched subjects were selected as the control group. One hundred six of 118 patients were enrolled. Pure tone audiometry revealed age-dependent high-frequency hearing loss in patients with Parkinson's disease compared with both normative values and values for healthy age- and sex-matched controls (75/106 [71%], χ(2) = 5.959, P = .02; 92/106 [86.8%] vs 60/106 [56.6%], χ(2) = 23.804, P < .001, respectively). Pure tone audiometry scores correlated with Hoehn and Yahr scale scores (P < .05). Brain stem auditory-evoked potentials were normal in all patients. Our patients with Parkinson's disease showed age-dependent peripheral, unilateral, or bilateral hearing impairment. Whether these auditory deficits are intrinsic to Parkinson's disease or secondary to a more complex impaired processing of sensorial inputs occurring over the course of illness remains to be determined. Because α-synuclein is located predominately in the efferent neuronal system within the inner ear, it could affect susceptibility to noise-induced hearing loss or presbycusis. It is feasible that the natural aging process combined with neurodegenerative changes intrinsic to Parkinson's disease might interfere with cochlear transduction mechanisms, thus anticipating presbycusis. PMID

  6. [Exercices program and rehabilitation of motor disorders in Parkinson's disease].

    PubMed

    Pélissier, J; Pérennou, D

    2000-01-01

    As long as motor disorders are controlled by DOPAtherapy, exercise programs and rehabilitation would not appear to be essential for patients suffering from Parkinson's disease. Such measures do become necessary however when secondary occurrence of motor decline develops. Physical medicine and rehabilitation have not been really involved in Parkinson's disease and few articles have assessed the value of these programs. In fact, controlled randomized studies have faced two kinds of methodological difficulties, those due to rehabilitation practices, and those due to Parkinson's disease specificity, especially similarities between groups for Hoehn and Yahr stage at study onset and unchanged drug treatment during the period of the clinical trial. Assessment has had to rely on scales taking into account the main Parkinson impairments (e.g. walking ability, postural control, skill), their intensity and also their fluctuation such as on-off effects. The Unified Parkinson's Disease Rating Scale (UPDRS) looks well-adapted but has been only recently for such studies. Many exercise programs, aiming at improving coordination, sway balance, transfer and gait have been proposed in the literature; rhythmic visual or auditory cueing seem quite effective. Only four controlled studies with satisfactory methodology are available. They could lead to the conclusion that physiotherapy would be effective more by reducing daily life disability than by improving Parkinson symptoms such as bradykinesia or tremor. To be effectively performed at home, these exercises would have to be taught early in the course of the disease and during an on phase, physiotherapists giving special attention to postural control and prevention of falls. In another controlled randomized study occupational therapists successfully trained patients in everyday activities. For the most severely impaired patients, rehabilitation and home adaptations are the only means to achieve an less dependent status

  7. The neurobiology of the spinal cord in experimental parkinsonism and Parkinson's disease.

    PubMed

    Ferrucci, Michela; Biagioni, Francesca; Vivacqua, Giorgio; Busceti, Carla Letizia; Bartalucci, Alessia; Soldani, Paola; D'Este, Loredana; Fumagalli, Lorenzo; Fornai, Francesco

    2013-12-01

    The neurobiology of non-motor symptoms in Parkinson's disease (PD) reveals a number of unexpected areas which once were not recognized a priori as part of the neuropathology underlying PD. These areas may belong either to central nervous system or periphery. Among central areas major efforts in the last decade led to recognize a number of brain nuclei as part of the disease spreading or disease onset in PD patients. Unexpectedly recent evidence deriving from pathological studies in PD patients and corroborated by experimental models of PD provided clear evidence that the spinal cord is often recruited in PD pathology. Such an involvement is intriguing since the major degenerative disease of the spinal cord (amyotrophic lateral sclerosis) features the involvement of dopaminergic neurons of the substantia nigra pars compacta, while some environmental (parkinsonism, ALS, and dementia of Guam) and genetic (Kufor-Rakeb syndrome) diseases are known to be characterized by mixed degeneration of pyramidal and extrapyramidal regions. Thus, the clear-cut between degeneration of dopaminergic neurons in the substantia nigra and the loss of pyramidal motor system appears now more as a continuum of   degeneration which converge in abnormal activity and cell pathology of motor neurons as a final common pathway. Among motor neurons, visceral efferent cells of the spinal cord are involved and provide a robust neurobiological findings which may justify a variety of non-motor autonomic symptoms which characterize PD. Neurodegeneration in the spinal cord extends to the dorsal horn of the grey matter posing an intriguing link between PD and sensory alterations. The present manuscript reviews the involvement of multiple regions of the spinal cord in PD and experimental parkinsonism in the attempt to provide both a neurobiological background to understand non motor symptoms and to provide the anatomical basis for disease spreading. PMID:24873929

  8. 77 FR 50549 - Agency Information Collection: Emergency Submission for OMB Review (Telehealth in the Parkinson's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-21

    ... AFFAIRS Agency Information Collection: Emergency Submission for OMB Review (Telehealth in the Parkinson's... for information needed to improve the care and clinical outcomes of patients with Parkinson's disease... ``Telehealth in the Parkinson's Disease Research, Education and Clinical Center (PADRECC): The Key to...

  9. Control effects of stimulus paradigms on characteristic firings of parkinsonism.

    PubMed

    Zhang, Honghui; Wang, Qingyun; Chen, Guanrong

    2014-09-01

    Experimental studies have shown that neuron population located in the basal ganglia of parkinsonian primates can exhibit characteristic firings with certain firing rates differing from normal brain activities. Motivated by recent experimental findings, we investigate the effects of various stimulation paradigms on the firing rates of parkinsonism based on the proposed dynamical models. Our results show that the closed-loop deep brain stimulation is superior in ameliorating the firing behaviors of the parkinsonism, and other control strategies have similar effects according to the observation of electrophysiological experiments. In addition, in conformity to physiological experiments, we found that there exists optimal delay of input in the closed-loop GPtrain|M1 paradigm, where more normal behaviors can be obtained. More interestingly, we observed that W-shaped curves of the firing rates always appear as stimulus delay varies. We furthermore verify the robustness of the obtained results by studying three pallidal discharge rates of the parkinsonism based on the conductance-based model, as well as the integrate-and-fire-or-burst model. Finally, we show that short-term plasticity can improve the firing rates and optimize the control effects on parkinsonism. Our conclusions may give more theoretical insight into Parkinson's disease studies. PMID:25273214

  10. Gaucher disease and comorbidities: B-cell malignancy and parkinsonism.

    PubMed

    Cox, Timothy M; Rosenbloom, Barry E; Barker, Roger A

    2015-07-01

    Data emerging from the International Collaborative Gaucher Group (ICGG) Gaucher Registry together with other contemporary clinical surveys have revealed a close association between Gaucher disease and non-Hodgkin's B-cell lymphoma and myeloma and Gaucher disease and Parkinson's disease. Several possible explanations for increased B-cell proliferation and neoplasia in Gaucher disease have been proposed, including the possible influence of sphingosine (derived from the extra lysosomal metabolism of glucosylceramide), gene modifiers, splenectomy and immune system deregulation induced by cytokines, chemokines, and hydrolases released from Gaucher cells. Parkinson's disease is frequently seen in the otherwise-healthy relatives of Gaucher disease patients leading to the finding that GBA mutations represent a genetic risk factor for Parkinson's disease. The mechanism of the association between GBA mutations and Parkinson's disease has yet to be elucidated but the pathogenesis appears distinct from that of Gaucher disease. Several pathogenic pathways have been proposed including lysosomal and/or mitochondrial dysfunction. The effect of Gaucher disease specific therapies on the incidence of cancer or Parkinson's disease are not clear and will likely be evaluated in future ICGG Gaucher Registry studies. PMID:26096744

  11. [Health-related quality of life in Parkinson's disease].

    PubMed

    Cano-de la Cuerda, Roberto; Vela-Desojo, Lydia; Miangolarra-Page, Juan C; Macías-Macías, Yolanda; Muñoz-Hellin, Elena

    2010-01-01

    Parkinson's disease is a disabling and progressive neurological condition characterized by multiple motor and non motor symptoms that contribute to deterioration in quality of life. The diversity of symptoms associated with the disease and its management affect the patients on their physical, social and mental quality of life. The aim of this study was to identify key dimensions of health related quality of life (HRQOL) in a population affected with Parkinson's disease with a degree of mild-moderate impairment. Thirty six patients with Parkinson were recruited. The Hoehn and Yarh scale, the Unified Parkinson's Disease Rate Scale, the scale of activities of daily life and Schwab & England Get Up & Go Test were applied. HRQOL was assessed with the EuroQol-5D and the specific questionnaire Parkinson's Disease Questionnaire-39 items. The dimensions of the PDQ-39, except the PDQ-39 Pain domain and the EuroQol-5D correlated significantly with the severity of the disease. HRQOL was correlated with the functional status of patients. Only the PDQ-39 pain domain correlated with the risk of falls. Our results suggest that the HRQOL of patients with PD, in a state of mild-moderate impairment, is strongly influenced by disease severity and functional status. PMID:21163736

  12. Challenges of treatment adherence in older patients with Parkinson's disease.

    PubMed

    Bainbridge, Jacquelyn L; Ruscin, J Mark

    2009-01-01

    Patient adherence to a medication regimen is critical to treatment outcome, quality of life and future healthcare costs. For elderly patients with Parkinson's disease, obstacles to adherence can be particularly complex. Beyond age-related and economic factors, elderly patients with Parkinson's disease often require complicated dosing or titration schedules and have multiple co-morbidities that necessitate administration of therapies from multiple drug classes. In addition, neuropsychiatric disturbances and cognitive impairment, which are often part of the disease process, can affect adherence, as can variable responses to anti-parkinsonian agents as the disease progresses. Several recent studies in patients with Parkinson's disease point to the need for establishing good adherence patterns early and maintaining these throughout the course of treatment. To achieve optimal adherence in elderly patients with Parkinson's disease, a combination of pharmacological and non-pharmacological approaches appears to be the best strategy for success. Examples include a strong provider-patient relationship, educational intervention by phone or face-to-face contact, simplified dosing and administration schedules, management and understanding of medication adverse events, and the use of adherence aids such as pill boxes and hour-by-hour organizational charts. Research into new avenues that include improved drug monitoring, pharmacogenetics and neuroprotective regimens may give rise to better adherence in elderly patients with Parkinson's disease in the future. PMID:19220071

  13. James Parkinson (1755-1824): a pioneer of child care.

    PubMed

    Pearn, J; Gardner-Thorpe, C

    2001-02-01

    James Parkinson (1755-1824) of Parkinson's disease, is well recognized as a pioneer of clinical neurology; and is even more famous as a founder of modern palaeontology. We have reviewed from primary sources his extensive contributions to clinical child care and his pioneering advocacy for child welfare, protection and safety. His writings, outreach and advocacy for children's health characterizes him as one whose influence was an important springboard from which evolved the modern specialty of paediatrics. Parkinson was one of the first to write on child-rearing practices and in this context antedated Benjamin Spock by 150 years. Parkinson was a pioneer of child safety and the prevention of childhood trauma. He wrote of the resuscitation of near-drowned children and of first aid for injured children. This critical analysis reviews his pioneering description of child abuse and the development of post-abuse hydrocephalus. He wrote the datum description (in English) of the pathophysiology and pathology of appendicitis in children, of fatal rabies in children and highlighted the risk of death even when the biting dog was not clinically rabid. His advocacy for social reform for children's welfare was courageous and pioneering. James Parkinson, hitherto unacknowledged, was a significant founder of the evolving discipline of paediatrics and child health. PMID:11168861

  14. Control effects of stimulus paradigms on characteristic firings of parkinsonism

    NASA Astrophysics Data System (ADS)

    Zhang, Honghui; Wang, Qingyun; Chen, Guanrong

    2014-09-01

    Experimental studies have shown that neuron population located in the basal ganglia of parkinsonian primates can exhibit characteristic firings with certain firing rates differing from normal brain activities. Motivated by recent experimental findings, we investigate the effects of various stimulation paradigms on the firing rates of parkinsonism based on the proposed dynamical models. Our results show that the closed-loop deep brain stimulation is superior in ameliorating the firing behaviors of the parkinsonism, and other control strategies have similar effects according to the observation of electrophysiological experiments. In addition, in conformity to physiological experiments, we found that there exists optimal delay of input in the closed-loop GPtrain|M1 paradigm, where more normal behaviors can be obtained. More interestingly, we observed that W-shaped curves of the firing rates always appear as stimulus delay varies. We furthermore verify the robustness of the obtained results by studying three pallidal discharge rates of the parkinsonism based on the conductance-based model, as well as the integrate-and-fire-or-burst model. Finally, we show that short-term plasticity can improve the firing rates and optimize the control effects on parkinsonism. Our conclusions may give more theoretical insight into Parkinson's disease studies.

  15. Living with Parkinson's and the Emerging Role of Occupational Therapy

    PubMed Central

    Jansa, Jelka; Aragon, Ana

    2015-01-01

    Parkinson's disease is a chronic and increasingly complex condition, demanding multidisciplinary management. Over the last twenty years or so, alongside the growth of specialist services and healthcare teams specifically developed for people with Parkinson's, occupational therapy has grown in recognition as a treatment option, especially since evidence of its efficacy is now slowly emerging. The purpose of this work is to outline the role of occupational therapy clinical practice in the management of people living with Parkinson's disease and its emergent evidence base, combined with details of current occupational therapy philosophy and process, as applicable to occupational therapy practice for people with Parkinson's. The Canadian Practice Process Framework is used to structure this overview and was selected because it is a well-recognized, evidence-based tool used by occupational therapists and encompasses the core concepts of human occupation and person-centred practice. The framework employed allows the flexibility to reflect the pragmatic occupational therapy intervention process and so enables the illustration of the individually tailored approach required to accommodate to the complex pathology and personal, domestic, and social impacts, affecting the functioning of Parkinson's disease patients on a daily basis. PMID:26495151

  16. The late positive potential, emotion and apathy in Parkinson's disease.

    PubMed

    Dietz, J; Bradley, M M; Jones, J; Okun, M S; Perlstein, W M; Bowers, D

    2013-04-01

    Parkinson's disease is associated with emotional changes including depression, apathy, and anxiety. The current study investigated emotional processing in non-demented individuals with Parkinson disease (PD) using an electrophysiological measure, the centro-parietal late positive potential (LPP). Non-demented patients with Parkinson's disease (n=17) and healthy control participants (n=16) viewed pleasant, neutral, and unpleasant pictures while EEG was recorded from a 64-channel geodesic net. The Parkinson patients did not differ from controls in terms of early electrophysiological components that index perceptual processing (occipital P100, N150, P250). Parkinson patients, however, showed reduced LPP amplitude specifically when viewing unpleasant, compared to pleasant, pictures as well as when compared to controls, consistent with previous studies suggesting a specific difference in aversive processing between PD patients and healthy controls. Importantly, LPP amplitude during unpleasant picture viewing was most attenuated for patients reporting high apathy. The data suggest that apathy in PD may be related to a deficit in defensive activation, and may be indexed cortically using event-related potentials. PMID:23320979

  17. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism.

    PubMed

    Schrag, Anette; Schott, Jonathan M

    2006-04-01

    In this review we discuss the epidemiological, clinical, and genetic characteristics of early-onset parkinsonism, defined as parkinsonism starting before age 40 (sometimes 50) years. Juvenile parkinsonism is very rare and is the result of various secondary or genetic causes. In patients with onset at or above age 21 years, secondary causes require exclusion but are rare; most cases with a fairly pure parkinsonian syndrome (eg, young-onset Parkinson's disease; YOPD) are due to typical Lewy-body Parkinson's disease or, less commonly, genetic causes. In comparison with patients with late-onset disease, most patients with YOPD progress more slowly in terms of motor features and have a longer disease course with preservation of cognitive function, but typically develop motor fluctuations and dyskinesias earlier. Patients with YOPD generally experience a greater effect in their lives than those with late onset, with poorer social adjustment, higher rates of depression, and lower quality of life. Management of YOPD must therefore aim to maintain occupational, social, and daily functioning, while delaying or ameliorating motor complications of treatment, providing psychological support, and, where possible, preventing psychiatric complications including depression. PMID:16545752

  18. Epidemiology of psychosis in Parkinson's disease.

    PubMed

    Fénelon, Gilles; Alves, Guido

    2010-02-15

    Psychotic symptoms are frequent and disabling in patients with Parkinson's disease (PD). Methodological issues in the epidemiology of PD associated psychosis (PDP) include differences in the symptoms assessed, the methods of assessment, and the selection of patients. Most studies are prospective clinic-based cross-sectional studies providing point prevalence rates in samples on dopaminergic treatment. Visual hallucinations are present in about one quarter to one third of the patients, auditory in up to 20%. Tactile/somatic, and olfactory hallucinations are usually not systematically sought. Minor phenomena such as sense of presence and visual illusions affect 17 to 72% of the patients, and delusions about 5%. Lifetime prevalence of visual hallucinations reaches approximately 50%. Prospective longitudinal cohort studies suggest that hallucinations persist and worsen in individual patients, and that their prevalence increases with time. A facilitating role of treatment on PDP is demonstrated at least for dopaminergic agonists, but there is no simple dose-effect relationship between dopaminergic treatment and the presence or severity of hallucinations. The main endogenous non-modifiable risk factor is cognitive impairment. Other associated factors include older age/longer duration of PD, disease severity, altered dream phenomena, daytime somnolence, and possibly depression and dysautonomia. PDP reduces quality of life in patients and increases caregiver distress, and is an independent risk factor for nursing home placement and development of dementia. PMID:19740486

  19. From micrographia to Parkinson's disease dysgraphia.

    PubMed

    Letanneux, Alban; Danna, Jeremy; Velay, Jean-Luc; Viallet, François; Pinto, Serge

    2014-10-01

    Micrographia, an abnormal reduction in writing size, is a specific behavioral deficit associated with Parkinson's disease (PD). In recent years, the availability of graphic tablets has made it possible to study micrographia in unprecedented detail. Consequently, a growing number of studies show that PD patients also exhibit impaired handwriting kinematics. Is micrographia still the most characteristic feature of PD-related handwriting deficits? To answer this question, we identified studies that investigated handwriting in PD, either with conventional pencil-and-paper measures or with graphic tablets, and we reported their findings on key spatiotemporal and kinematic variables. We found that kinematic variables (velocity, fluency) differentiate better between control participants and PD patients, and between off- and on-treatment PD patients, than the traditional measure of static writing size. Although reduced writing size is an important feature of PD handwriting, the deficit is not restricted to micrographia stricto sensu. Therefore, we propose the term PD dysgraphia, which encompasses all deficits characteristic of Parkinsonian handwriting. We conclude that the computerized analysis of handwriting movements is a simple and useful tool that can contribute to both diagnosis and follow-up of PD. PMID:25156696

  20. Neural correlates underlying micrographia in Parkinson's disease.

    PubMed

    Wu, Tao; Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. PMID:26525918

  1. Cell replacement therapy for Parkinson's disease.

    PubMed

    Wijeyekoon, Ruwani; Barker, Roger A

    2009-07-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the degeneration of dopaminergic neurons projecting from the substantia nigra to the striatum is a key pathological feature of the disease. Although pharmacological dopamine replacement is generally very effective in early disease, it is only a symptomatic therapy and can have significant side effects with long term use. One of the key strategies in a more restorative approach to PD therapy involves replacement of this degenerating nigro-striatal dopaminergic network with cells and several possible cell sources are being explored. While much experience and some success have been gained with fetal ventral mesencephalic (FVM) tissue transplants, the rapidly advancing stem cell field is providing attractive alternative options which circumvent many of the ethical and practical problems inherent in trials with FVM tissue. Of these embryonic stem cells and induced pluripotent stem cells seem the most promising. However further development and optimisation of the safety and efficacy of the techniques involved in generating and manipulating these, as well as other, cell sources will be essential before any further clinical trials are carried out. PMID:19007882

  2. Sleep disturbances in Alzheimer's and Parkinson's diseases.

    PubMed

    Rothman, Sarah M; Mattson, Mark P

    2012-09-01

    Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders and exact a burden on our society greater than cardiovascular disease and cancer combined. While cognitive and motor symptoms are used to define AD and PD, respectively, patients with both disorders exhibit sleep disturbances including insomnia, hypersomnia and excessive daytime napping. The molecular basis of perturbed sleep in AD and PD may involve damage to hypothalamic and brainstem nuclei that control sleep-wake cycles. Perturbations in neurotransmitter and hormone signaling (e.g., serotonin, norepinephrine and melatonin) and the neurotrophic factor BDNF likely contribute to the disease process. Abnormal accumulations of neurotoxic forms of amyloid β-peptide, tau and α-synuclein occur in brain regions involved in the regulation of sleep in AD and PD patients, and are sufficient to cause sleep disturbances in animal models of these neurodegenerative disorders. Disturbed regulation of sleep often occurs early in the course of AD and PD, and may contribute to the cognitive and motor symptoms. Treatments that target signaling pathways that control sleep have been shown to retard the disease process in animal models of AD and PD, suggesting a potential for such interventions in humans at risk for or in the early stages of these disorders. PMID:22552887

  3. Concurrent discrimination learning in Parkinson's disease.

    PubMed

    Moody, Teena D; Chang, Grace Y; Vanek, Zeba F; Knowlton, Barbara J

    2010-02-01

    Studies of neuropsychological patients and experimental animals have demonstrated that the striatum plays a role in implicit habit learning. Here, we examined the performance of patients with Parkinson's disease (PD) on a concurrent discrimination task that can be learned implicitly by neurologically intact individuals. Participants viewed a pair of shapes on each trial and, under a timed deadline, guessed which one concealed a smiling face. About half the control participants exhibited minimal awareness of the cue-reward relationships as assessed by a post-test evaluation. Nevertheless, these participants were able to perform the discrimination task; there was no correlation between awareness and performance on the task. In contrast, minimally aware patients with PD showed no learning, whereas those who were more aware of the relationships performed as well as control participants on the task. There was a significant correlation between awareness and performance in patients with PD. These data support the idea that the basal ganglia play a role in implicit habit learning and underscore the importance of using tests of awareness to assess the content and process of learning in humans. PMID:20141275

  4. The proteomic approach in Parkinson's disease.

    PubMed

    Fasano, Mauro; Bergamasco, Bruno; Lopiano, Leonardo

    2007-11-01

    Parkinson's disease (PD) is a complex, multifactorial neurodegenerative disease affecting about 2% of the population over 65 years. Etiopathogenetic mechanisms of PD are not fully understood, although a number of factors contributing to the selective degeneration of substantia nigra neurons have been identified, including mitochondrial dysfunction, proteasomal impairment, oxidative stress, excitotoxicity, and inflammation. Although a global view of the disease at the molecular level can be obtained only from the biochemical analysis of the affected human tissue, difficulties in obtaining human specimens of the affected area have limited substantially the number of reports published to date. Therefore, cellular and animal models of the disease have been developed to investigate single factors contributing to disease pathogenesis, e.g., protein aggregation or altered dopamine homeostasis. In this review, we report how proteomic methodologies have been used so far to investigate cellular and animal models of PD, as well as to compare postmortem specimens of substantia nigra of affected patients to that of control subjects. Proteomic studies concur to highlight the role of a compromised antioxidant defense in PD pathogenesis. The proteomic approach in the investigation of etiopathogenetic mechanisms of PD is still at its beginning, however, the findings reviewed here should serve as a useful foundation to further work. PMID:21136640

  5. Modeling proteasome dynamics in Parkinson's disease.

    PubMed

    Sneppen, Kim; Lizana, Ludvig; Jensen, Mogens H; Pigolotti, Simone; Otzen, Daniel

    2009-01-01

    In Parkinson's disease (PD), there is evidence that alpha-synuclein (alphaSN) aggregation is coupled to dysfunctional or overburdened protein quality control systems, in particular the ubiquitin-proteasome system. Here, we develop a simple dynamical model for the on-going conflict between alphaSN aggregation and the maintenance of a functional proteasome in the healthy cell, based on the premise that proteasomal activity can be titrated out by mature alphaSN fibrils and their protofilament precursors. In the presence of excess proteasomes the cell easily maintains homeostasis. However, when the ratio between the available proteasome and the alphaSN protofilaments is reduced below a threshold level, we predict a collapse of homeostasis and onset of oscillations in the proteasome concentration. Depleted proteasome opens for accumulation of oligomers. Our analysis suggests that the onset of PD is associated with a proteasome population that becomes occupied in periodic degradation of aggregates. This behavior is found to be the general state of a proteasome/chaperone system under pressure, and suggests new interpretations of other diseases where protein aggregation could stress elements of the protein quality control system. PMID:19411740

  6. Physiological Phenotype and Vulnerability in Parkinson's Disease

    PubMed Central

    Surmeier, D. James; Guzman, Jaime N.; Sanchez, Javier; Schumacker, Paul T.

    2012-01-01

    This review will focus on the principles underlying the hypothesis that neuronal physiological phenotype—how a neuron generates and regulates action potentials—makes a significant contribution to its vulnerability in Parkinson's disease (PD) and aging. A cornerstone of this hypothesis is that the maintenance of ionic gradients underlying excitability can pose a significant energetic burden for neurons, particularly those that have sustained residence times at depolarized membrane potentials, broad action potentials, prominent Ca2+ entry, and modest intrinsic Ca2+ buffering capacity. This energetic burden is shouldered in neurons primarily by mitochondria, the sites of cellular respiration. Mitochondrial respiration increases the production of damaging superoxide and other reactive oxygen species (ROS) that have widely been postulated to contribute to cellular aging and PD. Many of the genetic mutations and toxins associated with PD compromise mitochondrial function, providing a mechanistic linkage between known risk factors and cellular physiology that could explain the pattern of pathology in PD. Because much of the mitochondrial burden created by this at-risk phenotype is created by Ca2+ entry through L-type voltage-dependent channels for which there are antagonists approved for human use, a neuroprotective strategy to reduce this burden is feasible. PMID:22762023

  7. Dopaminergic Dysregulation, Artistic Expressiveness, and Parkinson's Disease

    PubMed Central

    López-Pousa, S.; Lombardía-Fernández, C.; Olmo, J. Garre; Monserrat-Vila, S.; Vilalta-Franch, J.; Calvó-Perxas, L.

    2012-01-01

    Background The most frequent behavioral manifestations in Parkinson's disease (PD) are attributed to the dopaminergic dysregulation syndrome (DDS), which is considered to be secondary to the iatrogenic effects of the drugs that replace dopamine. Over the past few years some cases of patients improving their creative abilities after starting treatment with dopaminergic pharmaceuticals have been reported. These effects have not been clearly associated to DDS, but a relationship has been pointed out. Methods Case study of a patient with PD. The evolution of her paintings along medication changes and disease advance has been analyzed. Results The patient showed a compulsive increase of pictorial production after the diagnosis of PD was made. She made her best paintings when treated with cabergolide, and while painting, she reported a feeling of well-being, with loss of awareness of the disease and reduction of physical limitations. Conclusions Dopaminergic antagonists (DA) trigger a dopaminergic dysfunction that alters artistic creativity in patients having a predisposition for it. The development of these skills might be due to the dopaminergic overstimulation due to the therapy with DA, which causes a neurophysiological alteration that globally determines DDS. PMID:23185168

  8. Predicting Parkinson's disease - why, when, and how?

    PubMed

    Postuma, R B; Montplaisir, J

    2009-12-01

    Parkinson's disease (PD) is a progressive disorder with a presymptomatic interval; that is, there is a period during which the pathologic process has begun, but motor signs required for the clinical diagnosis are absent. There is considerable interest in discovering markers to diagnose this preclinical stage. Current predictive marker development stems mainly from two principles; first, that pathologic processes occur in lower brainstem regions before substantia nigra involvement and second, that redundancy and compensatory responses cause symptoms to emerge only after advanced degeneration. Decreased olfaction has recently been demonstrated to predict PD in prospective pathologic studies, although the lead time may be relatively short and the positive predictive value and specificity are low. Screening patients for depression and personality changes, autonomic symptoms, subtle motor dysfunction on quantitative testing, sleepiness and insomnia are other potential simple markers. More invasive measures such as detailed autonomic testing, cardiac MIBG-scintigraphy, transcranial ultrasound, and dopaminergic functional imaging may be especially useful in those at high risk or for further defining risk in those identified through primary screening. Despite intriguing leads, direct testing of preclinical markers has been limited, mainly because there is no reliable way to identify preclinical disease. Idiopathic RBD is characterized by loss of normal atonia with REM sleep. Approximately 50% of affected individuals will develop PD or dementia within 10 years. This provides an unprecedented opportunity to test potential predictive markers before clinical disease onset. The results of marker testing in idiopathic RBD with its implications for disease prediction will be detailed. PMID:20082967

  9. Eryptosis as a marker of Parkinson's disease

    PubMed Central

    Pretorius, Etheresia; Swanepoel, Albe C; Buys, Antoinette V; Vermeulen, Natasha; Duim, Wiebren; Kell, Douglas B

    2014-01-01

    A major trend in recent Parkinson's disease (PD) research is the investigation of biological markers that could help in identifying at-risk individuals or to track disease progression and response to therapies. Central to this is the knowledge that inflammation is a known hallmark of PD and of many other degenerative diseases. In the current work, we focus on inflammatory signalling in PD, using a systems approach that allows us to look at the disease in a more holistic way. We discuss cyclooxygenases, prostaglandins, thromboxanes and also iron in PD. These particular signalling molecules are involved in PD pathophysiology, but are also very important in an aberrant coagulation/hematology system. We present and discuss a hypothesis regarding the possible interaction of these aberrant signalling molecules implicated in PD, and suggest that these molecules may affect the erythrocytes of PD patients. This would be observable as changes in the morphology of the RBCs and of PD patients relative to healthy controls. We then show that the RBCs of PD patients are indeed rather dramatically deranged in their morphology, exhibiting eryptosis (a kind of programmed cell death). This morphological indicator may have useful diagnostic and prognostic significance. PMID:25411230

  10. Modeling proteasome dynamics in Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Sneppen, Kim; Lizana, Ludvig; Jensen, Mogens H.; Pigolotti, Simone; Otzen, Daniel

    2009-09-01

    In Parkinson's disease (PD), there is evidence that α-synuclein (αSN) aggregation is coupled to dysfunctional or overburdened protein quality control systems, in particular the ubiquitin-proteasome system. Here, we develop a simple dynamical model for the on-going conflict between αSN aggregation and the maintenance of a functional proteasome in the healthy cell, based on the premise that proteasomal activity can be titrated out by mature αSN fibrils and their protofilament precursors. In the presence of excess proteasomes the cell easily maintains homeostasis. However, when the ratio between the available proteasome and the αSN protofilaments is reduced below a threshold level, we predict a collapse of homeostasis and onset of oscillations in the proteasome concentration. Depleted proteasome opens for accumulation of oligomers. Our analysis suggests that the onset of PD is associated with a proteasome population that becomes occupied in periodic degradation of aggregates. This behavior is found to be the general state of a proteasome/chaperone system under pressure, and suggests new interpretations of other diseases where protein aggregation could stress elements of the protein quality control system.

  11. Medication Adherence in People With Parkinson Disease.

    PubMed

    Shin, Ju Young; Habermann, Barbara

    2016-01-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. Because there is no cure for PD currently, pharmacological therapy is the mainstay of PD symptom management. Despite the importance of medication adherence in PD, several studies have reported medication nonadherence and/or suboptimal adherence. This literature review provides an overview of medication adherence issues in people with PD. Articles were identified for this study using computerized database searches and journal hand searches. Of the 72 medication adherence articles reviewed, the following articles were eligible for this review: (a) 10 articles measuring medication adherence in people with PD, (b) four medication adherence intervention articles, and (c) six studies of medication adherence in hospitalized settings. The importance of adherence assessment and strategies in improving medication adherence are discussed with the goal of improving symptom management and clinical outcomes in people with PD. Because medication taking is a complex and multifaceted phenomena, patient-centered, theory-driven interventions are needed to improve medication adherence and quality of care and life in people with PD. PMID:27224682

  12. Oral Health in Elders with Parkinson's Disease.

    PubMed

    Ribeiro, Giselle Rodrigues; Campos, Camila Heitor; Garcia, Renata Cunha Matheus Rodrigues

    2016-01-01

    This study aimed to evaluate objectively and subjectively the oral health of elders with Parkinson's disease (PD), using clinical oral assessments and the General Oral Health Assessment Index (GOHAI). Subjects included 37 removable prosthesis wearers, 17 with PD (mean age 69.59±5.09 years) and 20 without PD (mean age 72.00±5.69 years). The objective assessment included an evaluation of oral characteristics, including the number of remaining teeth, decayed, missing and filled teeth (DMFT), visible plaque index (VPI), salivary flow rate and removable prosthesis conditions. The subjective assessment included self-perception of oral health collected using the GOHAI index. The number of remaining teeth, DMFT, VPI, salivary flow rate and GOHAI data were compared between the groups using t-tests. Removable prosthesis conditions were analyzed using χ2 tests (p<0.05). There were no group differences in the number of remaining teeth, DMFT, VPI or salivary flow rate (p>0.05). Greater maxillary prosthesis defects were observed in the control group (p=0.037). GOHAI scores were low for the PD group and moderate for controls, yielding a group difference (p=0.04). In conclusion, elders with PD have similar oral health to controls. Although all elders had few remaining teeth, high DMFT and high VPI, PD elders had more negative self-perceptions of their oral health than did the controls. PMID:27224571

  13. Drooling in Parkinson's Disease: a review

    PubMed Central

    Srivanitchapoom, Prachaya; Pandey, Sanjay; Hallett, Mark

    2014-01-01

    Parkinson's disease (PD) is a neurodegenerative disease causing both motor and non-motor symptoms. Drooling, an excessive pooling and spillover of saliva out of the oral cavity, is one of the non-motor symptoms in PD patients that produces various negative physical and psychosocial consequences for patients and their caregivers. At present, the pathophysiology of drooling in PD is not completely certain; however, impaired intra-oral salivary clearance is likely the major contributor. There are neither standard diagnostic criteria nor standard severity assessment tools for evaluating drooling in PD. In accordance with the possible pathophysiology, dopaminergic agents have been used to improve salivary clearance; however, these agents are not completely effective in controlling drooling. Various pharmacological and nonpharmacological treatment options have been studied. Local injection with botulinum toxin serotypes A and B into major salivary glands is most effective to reduce drooling. Future research to explore the exact pathophysiology and develop standard diagnostic criteria and standard severity assessment tools are needed to formulate specific treatment options and improve patient care. PMID:25200111

  14. The prediagnostic phase of Parkinson's disease.

    PubMed

    Noyce, Alastair John; Lees, Andrew John; Schrag, Anette-Eleonore

    2016-08-01

    The field of prediagnostic Parkinson's disease (PD) is fast moving with an expanding range of clinical and laboratory biomarkers, and multiple strategies seeking to discover those in the earliest stages or those 'at risk'. It is widely believed that the highest likelihood of securing neuroprotective benefit from drugs will be in these subjects, preceding current point of diagnosis of PD. In this review, we outline current knowledge of the prediagnostic phase of PD, including an up-to-date review of risk factors (genetic and environmental), their relative influence, and clinical features that occur prior to diagnosis. We discuss imaging markers across a range of modalities, and the emerging literature on fluid and peripheral tissue biomarkers. We then explore current initiatives to identify individuals at risk or in the earliest stages that might be candidates for future clinical trials, what we are learning from these initiatives, and how these studies will bring the field closer to realistically commencing primary or secondary preventive trials for PD. Further progress in this field hinges on greater clinical and biological description, and understanding of the prediagnostic, peridiagnostic and immediate postdiagnostic stages of PD. Identifying subjects 3-5 years before they are currently diagnosed may be an ideal group for neuroprotective trials. At the very least, these initiatives will help clarify the stage before and around diagnosis, enabling the field to push into unchartered territory at the earliest stages of disease. PMID:26848171

  15. Modeling neural circuits in Parkinson's disease.

    PubMed

    Psiha, Maria; Vlamos, Panayiotis

    2015-01-01

    Parkinson's disease (PD) is caused by abnormal neural activity of the basal ganglia which are connected to the cerebral cortex in the brain surface through complex neural circuits. For a better understanding of the pathophysiological mechanisms of PD, it is important to identify the underlying PD neural circuits, and to pinpoint the precise nature of the crucial aberrations in these circuits. In this paper, the general architecture of a hybrid Multilayer Perceptron (MLP) network for modeling the neural circuits in PD is presented. The main idea of the proposed approach is to divide the parkinsonian neural circuitry system into three discrete subsystems: the external stimuli subsystem, the life-threatening events subsystem, and the basal ganglia subsystem. The proposed model, which includes the key roles of brain neural circuit in PD, is based on both feed-back and feed-forward neural networks. Specifically, a three-layer MLP neural network with feedback in the second layer was designed. The feedback in the second layer of this model simulates the dopamine modulatory effect of compacta on striatum. PMID:25416983

  16. Online multimedia teaching tool for Parkinson's disease.

    PubMed

    Misiaszek, Greg; Riconscente, Michelle; Henke, Maria; Walsh, John P

    2008-01-01

    We developed an online multimedia tool designed to enhance the student-learning environment in neurosciences through multi-sensory engagement. The combined use of scrolling text, narrations, and visual imagery engages multiple sensory modalities for effective learning, and it assists students in visualizing complex processes in the nervous system. The initial rollout of the online tool is for instruction in Parkinson's disease (PD), but its structure is flexible and can be used for teaching a variety of subjects. The instructor can access the tool online during lecture, and students can access the same information via the internet outside of class. In addition, each chapter is stand-alone and thus can be accessed online by other faculty or students to supplement other courses. Within each chapter or module, information is presented in outline format with greater detail accessible via sequential drop-down menus. This layering of related topics creates a spatial and motor-accessed path for learning. These multiple forms of engagement offer rich information representations to improve students' knowledge encoding, storing, and retrieval via multiple pathways. For instance, the tool includes student-controlled 2-D and 3-D animations, and video clip demonstrations of both patient case studies and on-campus research projects directly related to the subject material. Supplemental readings consist of current research articles (in Adobe Acrobat PDF file format) accessed within each educational topic. The teaching tool for PD is online at http://geroauen.usc.edu/Gero414_Beta/. PMID:23493487

  17. Altered Pharyngeal Muscles in Parkinson Disease

    PubMed Central

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Beach, Thomas G.

    2012-01-01

    Dysphagia (impaired swallowing) is common in Parkinson disease (PD) patients and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor (PC) and cricopharyngeal (CP) sphincter muscles in postmortem specimens from 8 PD and 4 age-matched control patients. Pharyngeal muscles in PD patients exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, the PD patients with dysphagia had a higher percentage of atrophic myofibers vs. with those without dysphagia and controls. The fast-to-slow fiber type transition is consistent with abnormalities in swallowing, slow movement of food and increased tone in the CP sphincter in PD patients. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in PD patients. PMID:22588389

  18. Traversing a wormhole to combat Parkinson's disease.

    PubMed

    Caldwell, Guy A; Caldwell, Kim A

    2008-01-01

    Human movement disorders represent a significant and unresolved societal burden. Among these, the most prevalent is Parkinson's disease (PD), a disorder afflicting millions worldwide. Despite major advances, stemming primarily from human genetics, there remains a significant gap in our understanding of what factors underlie disease susceptibility, onset, and progression. Innovative strategies to discern specific intracellular targets for subsequent drug development are needed to more rapidly translate basic findings to the clinic. Here we briefly review the recent contributions of research using the nematode roundworm Caenorhabditis elegans as a model system for identifying and characterizing gene products associated with PD. As a microscopic but multicellular and genetically tractable animal with a well-defined nervous system and an experimentally tenable lifespan, C. elegans affords significant advantages to researchers attempting to determine causative and therapeutic factors that influence neuronal dysfunction and age-associated neurodegeneration. The rapidity with which traditional genetic, large-scale genomic, and pharmacological screening can be applied to C. elegans epitomizes the utility of this animal for disease research. Moreover, with mature bioinformatic and functional genomic data readily available, the nematode is well positioned to play an increasingly important role in PD-associated discoveries. PMID:19048050

  19. Associations between B Vitamins and Parkinson's Disease.

    PubMed

    Shen, Liang

    2015-09-01

    B vitamins may correlate with Parkinson's disease (PD) through regulating homocysteine level. However, there is no comprehensive assessment on the associations between PD and B vitamins. The present study was designed to perform a meta-analytic assessment of the associations between folate, vitamin B6, and vitamin B12 and PD, including the status of B vitamins in PD patients compared with controls, and associations of dietary intakes of B vitamins and risk of PD. A literature search using Medline database obtained 10 eligible studies included in the meta-analyses. Stata 12.0 statistical software was used to perform the meta-analysis. Pooled data revealed that there was no obvious difference in folate level between PD patients and healthy controls, and PD patients had lower level of vitamin B12 than controls. Available data suggested that higher dietary intake of vitamin B6 was associated with a decreased risk of PD (odds ratio (OR) = 0.65, 95% confidence intervals (CI) = (0.30, 1.01)), while no significant association was observed for dietary intake of folate and vitamin B12 and risk of PD. PD patients had lower level of vitamin B12 and similar level of folate compared with controls. Dietary intake of vitamin B6 exhibited preventive effect of developing PD based on the available data. As the number of included studies is limited, more studies are needed to confirm the findings and elucidate the underpinning underlying these associations. PMID:26343714

  20. Gastric electromechanical dysfunction in Parkinson's disease.

    PubMed

    Krygowska-Wajs, A; Lorens, K; Thor, P; Szczudlik, A; Konturek, S

    2000-01-01

    This study was designed to evaluate gastric myoelectrical and mechanical activities in idiopathic Parkinson's disease (IPD) patients. Twenty patients with IPD (14 male and 6 female, mean age 42 +/- 9 years) were studied. Patients were divided into two groups: group A--early stage of disease (no. = 6) and group B--advanced IPD (no. = 14). Electrogastrography (EGG) was performed in fasting and postprandial conditions (Synectics system). The cross-sectional area of the gastric antrum was measured by sonography (Hitachi EUB-240). The antral area in fasting conditions was 2.1 +/- 0.4 and 4.2 +/- 1.2 cm2 and gastric emptying was 75 +/- 5 and 125 +/- 12 min in groups A and B respectively. EGG showed dysrhythmias (range 1-6 cycles per minute) in about 75% of both groups of IPD patients without increase in signal amplitude after a meal. Our results suggest that gastric motility is particularly impaired in patients with advanced IPD. It may be caused by the primary degenerative process in the autonomic nervous system of the gut. PMID:10842759

  1. Theory of Mind in Parkinson's disease.

    PubMed

    Freedman, Morris; Stuss, Donald T

    2011-11-15

    Theory of Mind is an important concept within social cognition and refers to the ability to attribute mental states to oneself and others. Other terms for this concept include mentalizing and mind reading. Deficits in Theory of Mind may contribute to behavioral abnormalities, such as paranoia and delusions that are common in dementia. There are several experimental tasks for measuring Theory of Mind. A classical example is the false belief test. Examples of other measures include tests of understanding metaphor, sarcasm, irony, deception, and faux pas, determining what a person is thinking or feeling from photographs of the eye region, and visual perspective taking. There are several anatomical areas related to Theory of Mind. These include regions within the frontal and temporal lobes, and temporoparietal junction. There is a small but emerging literature on Theory of Mind in Parkinson's disease (PD). The data suggest that Theory of Mind is impaired in PD and that the deficits precede the development of dementia. Future studies are needed to better define the nature of the Theory of Mind deficits in PD, as well as the impact of these deficits on clinical disability in this disorder. PMID:21705020

  2. Multimodal Imaging Signatures of Parkinson's Disease

    PubMed Central

    Bowman, F. DuBois; Drake, Daniel F.; Huddleston, Daniel E.

    2016-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disorder that manifests through hallmark motor symptoms, often accompanied by a range of non-motor symptoms. There is a putative delay between the onset of the neurodegenerative process, marked by the death of dopamine-producing cells, and the onset of motor symptoms, creating an urgent need to develop biomarkers that may yield early PD detection. Neuroimaging offers a non-invasive approach to examining the potential utility of a vast number of functional and structural brain characteristics as biomarkers. We present a statistical framework for analyzing neuroimaging data from multiple modalities to determine features that reliably distinguish PD patients from healthy control (HC) subjects. Our approach builds on elastic net, performing regularization and variable selection, while introducing additional criteria centering on parsimony and reproducibility. We apply our method to data from 42 subjects (28 PD patients and 14 HC). Our approach demonstrates extremely high accuracy, assessed via cross-validation, and isolates brain regions that are implicated in the neurodegenerative PD process. PMID:27147942

  3. Animal Models of Parkinson's Disease: Vertebrate Genetics

    PubMed Central

    Lee, Yunjong; Dawson, Valina L.; Dawson, Ted M.

    2012-01-01

    Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially mice, have aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of showing a broad range of phenotypes and, coupled with their conserved genetic and anatomical structures, provide unparalleled molecular and pathological tools to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. Here, we provide an overview of the generation and characterization of transgenic and knockout mice used to study PD followed by a review of the molecular insights that have been gleaned from current PD mouse models. Finally, potential approaches to refine and improve current models are discussed. PMID:22960626

  4. Cellular Repair Strategies in Parkinson's Disease

    PubMed Central

    Winner, Beate; Vogt-Weisenhorn, Daniela M.; Lie, Chichung D.; Winkler, Jürgen

    2009-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 0.7% of the elderly population (defined as over 65 years of age). PD is clinically characterized by resting tremor, muscular rigidity, hypokinesia and postural instability. These motor symptoms result largely from the deficiency or dysfunction of dopaminergic neurons in the substantia nigra. Histopathological analysis reveals depletion of dopaminergic neurons as well as eosinophilic intracytoplasmic inclusions (Lewy bodies) in surviving neurons of the substantia nigra and other brain regions. The molecular pathogenesis is linked to protein misfolding by compromised alpha-synuclein and/or related proteins (synucleinopathy). Therefore, successful therapy of motor symptoms aims for the restoration of dopaminergic neurotransmission. Pharmacological drug treatment is usually effective only at an early stage of the disease but cannot halt progressive neuronal degeneration. With recent developments in stem cell technology, cell repair or replacement approaches came into focus. Here, we review new therapeutic strategies resulting from the innate propensity of the adult brain to generate new neurons, either by pharmacological stimulation of endogenous adult stem cell population or exogenous cell transplantation modalities. PMID:21180641

  5. Delayed gastric emptying in Parkinson's disease.

    PubMed

    Marrinan, Sarah; Emmanuel, Anton V; Burn, David J

    2014-01-01

    Gastrointestinal symptoms are evident in all stages of Parkinson's disease (PD). Most of the gastrointestinal abnormalities associated with PD are attributable to impaired motility. At the level of the stomach, this results in delayed gastric emptying. The etiology of delayed gastric emptying in PD is probably multifactorial but is at least partly related to Lewy pathology in the enteric nervous system and discrete brainstem nuclei. Delayed gastric emptying occurs in both early and advanced PD but is underdetected in routine clinical practice. Recognition of delayed gastric emptying is important because it can cause an array of upper gastrointestinal symptoms, but additionally it has important implications for the absorption and action of levodopa. Delayed gastric emptying contributes significantly to response fluctuations seen in people on long-term l-dopa therapy. Neurohormonal aspects of the brain-gut axis are pertinent to discussions regarding the pathophysiology of delayed gastric emptying in PD and are also hypothesized to contribute to the pathogenesis of PD itself. Ghrelin is a gastric-derived hormone with potential as a therapeutic agent for delayed gastric emptying and also as a novel neuroprotective agent in PD. Recent findings relating to ghrelin in the context of PD and gastric emptying are considered. This article highlights the pathological abnormalities that may account for delayed gastric emptying in PD. It also considers the wider relevance of abnormal gastric pathology to our current understanding of the etiology of PD. PMID:24151126

  6. Prospects of statins in Parkinson disease.

    PubMed

    Roy, Avik; Pahan, Kalipada

    2011-06-01

    Parkinson disease (PD) is second only to Alzheimer disease as the most common neurodegenerative disorder in humans. Despite intense investigations, no effective therapy is available to halt the progression of PD. Although statins are widely used cholesterol-lowering drugs throughout the world, recent studies suggest that these drugs modulate neurodegeneration-related signaling processes and may be beneficial for PD. Simvastatin is the most potent statin in crossing the blood-brain barrier, and this particular statin drug negatively correlates with the incidence of PD and shows efficacy in animal models of PD. However, PD mainly occurs in the aging population, who are more vulnerable to cholesterol or lipid-related disorders, raising questions whether this possible beneficial effect of statins in PD patients is cholesterol dependent or cholesterol independent. This article presents data on the therapeutic efficacy of simvastatin in a chronic MPTP model of PD, reviews recent literature, and discusses the pros and cons of statin therapy in PD. PMID:21252380

  7. Pragmatic comprehension deficit in Parkinson's disease.

    PubMed

    Holtgraves, Thomas; McNamara, Patrick

    2010-04-01

    Recognizing the specific speech act (Searle, 1969) that a speaker performs with an utterance is a fundamental feature of pragmatic competence. However, little is known about neurocognitive mediation of speech act comprehension. The present research examined the extent to which people with Parkinson's disease (PD) comprehend specific speech acts. In the first experiment, participants read conversational utterances and then performed a lexical decision task (decide whether a target string of letters was a word). Consistent with past research, nonimpaired participants performed this task more quickly when the target string was the speech act associated with the preceding utterance. In contrast, people with PD did not demonstrate this effect, suggesting that speech act activation is slowed or is not an automatic component of comprehension for people with PD. In a second study, participants were given unlimited time to indicate their recognition of the speech act performed with an utterance. PD participants were significantly poorer at this task than were control participants. We conclude that a previously undocumented language disorder exists in PD and that this disorder involves a selective deficit in speech act comprehension. Frontostriatal systems (the systems impaired in PD) likely contribute to normal speech act comprehension. PMID:19763993

  8. Improving Symptom Control in Early Parkinson's Disease

    PubMed Central

    Hauser, Robert A.

    2009-01-01

    Motor symptoms in Parkinson's disease (PD) are caused by a severe loss of pigmented dopamine-producing nigro-striatal neurons. Symptomatic therapies provide benefit for motor features by restoring dopamine receptor stimulation. Studies have demonstrated that delaying the introduction of dopaminergic medical therapy is associated with a rapid decline in quality of life. Nonmotor symptoms, such as depression, are common in early PD and also affect quality of life. Therefore, dopaminergic therapy should typically be initiated at, or shortly following, diagnosis. Monamine oxidase-B inhibitors provide mild symptomatic benefit, have excellent side effect profiles, and may improve long-term outcomes, making them an important first-line treatment option. Dopamine agonists (DAs) provide moderate symptomatic benefit but are associated with more side effects than levodopa. However, they delay the development of motor complications by delaying the need for levodopa. Levodopa (LD) is the most efficacious medication, but its chronic use is associated with the development of motor complications that can be difficult to resolve. Younger patients are more likely to develop levodopa-induced motor complications and they are therefore often treated with a DA before levodopa is added. For older patients, levodopa provides good motor benefit with a relatively low-risk of motor complications. Using levodopa with a dopa-decarboxylase inhibitor lessens adverse effects, and further adding a catechol-O-methyl transferase inhibitor can improve symptom control. PMID:21180628

  9. Metabotropic Glutamate Receptors for Parkinson's Disease Therapy

    PubMed Central

    Gasparini, Fabrizio; Di Paolo, Thérèse; Gomez-Mancilla, Baltazar

    2013-01-01

    Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson's disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD. PMID:23853735

  10. Hypothesis: Somatic Mosaicism and Parkinson Disease

    PubMed Central

    Kim, Han-Joon

    2014-01-01

    Mutations causing genetic disorders can occur during mitotic cell division after fertilization, which is called somatic mutations. This leads to somatic mosaicism, where two or more genetically distinct cells are present in one individual. Somatic mutations are the most well studied in cancer where it plays an important role and also have been associated with some neurodegenerative disorders. The study of somatic mosaicism in Parkinson disease (PD) is only in its infancy, and a case with somatic mutation has not yet been described. However, we can speculate that a somatic mutation affecting cells in the central nervous system including substantia nigra dopaminergic neurons could lead to the development of PD through the same pathomechanisms of genetic PD even in the absence of a germ-line mutation. Theoretically, a number of genes could be candidates for genetic analysis for the presence of somatic mosaicism. Among them, SNCA and PARK2 could be the best candidates to analyze. Because analyzing brain tissues in living patients is impossible, alternative tissues could be used to indicate the genetic status of the brain. Performance of the technology is another factor to consider when analyzing the tissues. PMID:25548528

  11. Multimodal Imaging Signatures of Parkinson's Disease.

    PubMed

    Bowman, F DuBois; Drake, Daniel F; Huddleston, Daniel E

    2016-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disorder that manifests through hallmark motor symptoms, often accompanied by a range of non-motor symptoms. There is a putative delay between the onset of the neurodegenerative process, marked by the death of dopamine-producing cells, and the onset of motor symptoms, creating an urgent need to develop biomarkers that may yield early PD detection. Neuroimaging offers a non-invasive approach to examining the potential utility of a vast number of functional and structural brain characteristics as biomarkers. We present a statistical framework for analyzing neuroimaging data from multiple modalities to determine features that reliably distinguish PD patients from healthy control (HC) subjects. Our approach builds on elastic net, performing regularization and variable selection, while introducing additional criteria centering on parsimony and reproducibility. We apply our method to data from 42 subjects (28 PD patients and 14 HC). Our approach demonstrates extremely high accuracy, assessed via cross-validation, and isolates brain regions that are implicated in the neurodegenerative PD process. PMID:27147942

  12. The natural history of Parkinson's disease.

    PubMed

    Poewe, W H; Wenning, G K

    1998-09-01

    There are still insufficient data on the natural course of Parkinson's disease (PD) owing to lack of standardized longitudinal follow-up studies. Reported progression rates in early PD vary considerably by a factor of 2 to 3. Similarly, data from sequential [18F]dopa PET studies in PD patients have produced variable decline rates of PET indices ranging between 7 and 70% per decade. Risk factors for rapid progression include old age at onset, concomitant major depression, dementia, and akinetic-rigid symptom presentation. The introduction of levodopa into the routine treatment of PD patients had a dramatic impact on symptomatic control without affecting the underlying rate of disease progression. By contrast, monoamine oxidase (MAO) B inhibition by deprenyl monotherapy in early PD was shown to delay the need for levodopa by around 9 months. However, the neuroprotective action disappeared after 2 years of follow-up. Furthermore, deprenyl also failed to influence the subsequent development of levodopa-induced motor complications. Available studies on mortality in PD provide heterogeneous mortality rates, probably because of discrepancies between patient populations with respect to co-morbidity, disease stage at study entry, and diagnostic accuracy. However, the most recent follow-up from the DATATOP cohort suggests normal life expectancy in carefully selected patients without significant co-morbidity and with adequate treatment and expert follow-up. PMID:9749568

  13. Non-motor symptoms in Parkinson's disease.

    PubMed

    Poewe, W

    2008-04-01

    Although still considered a paradigmatic movement disorder, Parkinson's disease (PD) is associated with a broad spectrum of non-motor symptoms. These include disorders of mood and affect with apathy, anhedonia and depression, cognitive dysfunction and hallucinosis, as well as complex behavioural disorders. Sensory dysfunction with hyposmia or pain is almost universal, as are disturbances of sleep-wake cycle regulation. Autonomic dysfunction including orthostatic hypotension, urogenital dysfunction and constipation is also present to some degree in a majority of patients. Whilst overall non-motor symptoms become increasingly prevalent with advancing disease, many of them can also antedate the first occurrence of motor signs - most notably depression, hyposmia or rapid eye movement sleep behaviour disorder (RBD). Although exact clinicopathological correlations for most of these non-motor features are still poorly understood, the occurrence of constipation, RBD or hyposmia prior to the onset of clinically overt motor dysfunction would appear consistent with the ascending hypothesis of PD pathology proposed by Braak and colleagues. Screening these early non-motor features might, therefore, be one approach towards early 'preclinical' diagnosis of PD. This review article provides an overview of the clinical spectrum of non-motor symptoms in PD together with a brief review of treatment options. PMID:18353132

  14. Diagnostic aspects of early Parkinson's disease.

    PubMed

    Müller, Thomas; Fuchs, Gerd; Hahne, Matthias; Klein, Wolfgang; Schwarz, Michael

    2006-08-01

    Insidious onset of mild, unspecific, sensitive, vegetative, psychopathological, cognitive and perceptive disturbances, i. e., visual and olfactory dysfunction, with a resulting change of personal behavior, i. e., reduced stress tolerance, precede the initially intermittently occurring motor symptoms in patients with Parkinson's disease (PD). Novel neuropathological findings suggest an expansion pattern of the neurodegenerative process beyond the nigral dopaminergic neurons with the initial event located outside the brain. This underlines the clinical concept of an initial premotor phase, which starts in nondopaminergic areas in PD. Moreover a more global general understanding of chronic neurodegeneration enables the performance of clinical trials on neuroprotection, since there is increasing evidence that diagnosis of PD at the threshold of onset of motor symptoms or cognitive symptoms in Alzheimer's disease is too late. Such an earlier diagnosis of chronic neurodegeneration will allow a more convincing demonstration of the efficacy of a neuroprotective or disease modifying compound. It will also support the concept of a clinically effective pharmacological intervention on a disease process, which is also more and more demanded by the health authorities for drug approval. PMID:16944354

  15. [Future standards in diagnosing Parkinson syndrome].

    PubMed

    Reichmann, H

    2010-03-01

    So far, the diagnosis of an idiopathic Parkinson-syndrome was based on the British Brain Bank Criteria, that is the occurrence of bradykinesia together with at least one more of the cardinal symptoms, i. e. resting tremor, rigidity or postural instability. The latter symptom is not useful, since it occurs only in the Hoehn and Yahr stage III which is seen in advanced PD patients. Thus, this symptom is certainly not useful for EARLY diagnosis. Early signs for PD are hyposmia, constipation, REM sleep behaviour disorder and depression. Early diagnosis is still a clinical one, which can be supported by a levodopa test. It can be expected that in the near future gene chips will be available for patients with a positive family history for PD or with an early onset. As long as a blood test for PD is not available, methods such as SPECT and PET are extremely useful in patients with an unclear clinical symptomatology. In my own view, each PD patient should receive once in his career a cranial CT or MRI. PMID:20195942

  16. The neurobiology of dysautonomia in Parkinson's disease.

    PubMed

    Natale, Gianfranco; Biagioni, Francesca; Vivacqua, Giorgio; D'Este, Loredana; Fumagalli, Lorenzo; Fornai, Francesco

    2013-12-01

    Neurodegenerative diseases (NDs) include a large variety of disorders that affects specific areas of the centralnervous system, leading to psychiatric and movement pathologies. A common feature that characterizes thesedisorders is the neuronal formation and accumulation of misfolded protein aggregates that lead to cell death. Inparticular, different proteinaceous aggregates accumulate to trigger a variety of clinical manifestations: prionprotein (PrPSc) in prion diseases, β-amyloid (Aβ) in Alzheimer's disease (AD), α-synuclein in Parkinson's disease(PD), huntingtin in Huntington's disease (HD), superoxide dismutase and TDP-43 in amyotrophic lateral sclerosis(ALS), tau in tauopathies. Non-motor alterations also occur in several viscera, in particular the gastrointestinaltract. These often precede the onset of motor symptoms by several years. For this reason, dysautonomic changescan be predictive of NDs and their correct recognition is being assuming a remarkable importance. This peculiarfeature led more and more to the concept that neurodegeneration may initiate in the periphery and propagate retrogradelytowards the central nervous system in a prion-like manner. In recent years, a particular attention wasdedicated to the clinical assessment of autonomic disorders in patients affected by NDs. In this respect, experimentalanimal models have been developed to understand the neurobiology underlying these effects as well as toinvestigate autonomic changes in peripheral organs. This review summarizes experimental studies that have beencarried out to understand autonomic symptoms in NDs, with the purpose to provide appropriate tools for comprehensiveand integrated studies. PMID:24873928

  17. Parkinson's disease in the older patient.

    PubMed

    Lewis, Simon J; Gangadharan, Sanjay; Padmakumar, Chandrasekhara Pillai

    2016-08-01

    Parkinson's disease (PD) is the second most commonly encountered neurodegenerative condition in clinical practice and probably offers a significantly greater variety of challenges than the management of Alzheimer's disease. As with most neurodegenerative diseases, age represents the leading risk factor for the development of PD. Current estimates would suggest that PD affects 1-2% of people over the age of 65 years and each decade sees an increasing number of cases. In addition, it is well recognised that most industrialised nations have an increasing proportion of individuals living longer. For example, recent data from Australia indicates that the prevalence of PD is anticipated to rise by 80% over the next 20 years and as such, we must all strive towards improving our clinical management of this common condition. In this article, we will attempt to highlight the issues that should be actively sought out and, where possible, addressed. We hope that an improved level of understanding will lead to better outcomes in older patients with PD. PMID:27481385

  18. Disease-modifying strategies for Parkinson's disease.

    PubMed

    Kalia, Lorraine V; Kalia, Suneil K; Lang, Anthony E

    2015-09-15

    Parkinson's disease (PD) is an increasingly prevalent and progressively disabling neurodegenerative disease. The impact of PD on patients and their families as well as its burden on health care systems could be substantially reduced by disease-modifying therapies that slow the rate of neurodegeneration or stop the disease process. Multiple agents have been studied in clinical trials designed to assess disease modification in PD, but all have failed. Over the last 3 years, clinical trials investigating the potential of adeno-associated virus serotype 2 (AAV)-neuturin, coenzyme Q10, creatine, pramipexole, and pioglitazone reported negative findings or futility. Despite these disappointments, progress has been made by expanding our understanding of molecular pathways involved in PD to reveal new targets, and by developing novel animal models of PD for preclinical studies. Currently, at least eight ongoing clinical trials are testing the promise of isradipine, caffeine, nicotine, glutathione, AAV2-glial cell-line derived neurotrophic factor (GDNF), as well as active and passive immunization against α-synuclein (α-Syn). In this review, we summarize the clinical trials of disease-modifying therapies for PD that were published since 2013 as well as clinical trials currently in progress. We also discuss promising approaches and ongoing challenges in this area of PD research. PMID:26208210

  19. Parkinson's disease and sleep/wake disturbances.

    PubMed

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2015-03-01

    Sleep disturbances are a common non-motor feature in patients with Parkinson's disease (PD). Early diagnosis and appropriate management are imperative for enhancing patient quality of life. Sleep disturbances can be caused by multiple factors in addition to age-related changes in sleep, such as nocturnal motor symptoms (rigidity, resting tremor, akinesia, tardive dyskinesia, and the "wearing off" phenomenon), non-motor symptoms (pain, hallucination, and psychosis), nocturia, and medication. Disease-related pathology involving the brainstem and changes in the neurotransmitter systems (norepinephrine, serotonin, and acetylcholine) responsible for regulating sleep structure and the sleep/wake cycle play a role in emerging excessive daytime sleepiness and sleep disturbances. Additionally, screening for sleep apnea syndrome, rapid eye movement sleep behavior disorder, and restless legs syndrome is clinically important. Questionnaire-based assessment utilizing the PD Sleep Scale-2 is useful for screening PD-related nocturnal symptoms. In this review, we focus on the current understanding and management of sleep disturbances in PD. PMID:25687697

  20. Monoamine Reuptake Inhibitors in Parkinson's Disease

    PubMed Central

    Huot, Philippe; Fox, Susan H.; Brotchie, Jonathan M.

    2015-01-01

    The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia. PMID:25810948

  1. The prediagnostic phase of Parkinson's disease

    PubMed Central

    Noyce, Alastair John; Lees, Andrew John; Schrag, Anette-Eleonore

    2016-01-01

    The field of prediagnostic Parkinson's disease (PD) is fast moving with an expanding range of clinical and laboratory biomarkers, and multiple strategies seeking to discover those in the earliest stages or those ‘at risk’. It is widely believed that the highest likelihood of securing neuroprotective benefit from drugs will be in these subjects, preceding current point of diagnosis of PD. In this review, we outline current knowledge of the prediagnostic phase of PD, including an up-to-date review of risk factors (genetic and environmental), their relative influence, and clinical features that occur prior to diagnosis. We discuss imaging markers across a range of modalities, and the emerging literature on fluid and peripheral tissue biomarkers. We then explore current initiatives to identify individuals at risk or in the earliest stages that might be candidates for future clinical trials, what we are learning from these initiatives, and how these studies will bring the field closer to realistically commencing primary or secondary preventive trials for PD. Further progress in this field hinges on greater clinical and biological description, and understanding of the prediagnostic, peridiagnostic and immediate postdiagnostic stages of PD. Identifying subjects 3–5 years before they are currently diagnosed may be an ideal group for neuroprotective trials. At the very least, these initiatives will help clarify the stage before and around diagnosis, enabling the field to push into unchartered territory at the earliest stages of disease. PMID:26848171

  2. Action verbal fluency in Parkinson's patients.

    PubMed

    Rodrigues, Inês Tello; Ferreira, Joaquim J; Coelho, Miguel; Rosa, Mario M; Castro-Caldas, Alexandre

    2015-06-01

    We compared the performance of 31 non-demented Parkinson's disease (PD) patients to 61 healthy controls in an action verbal fluency task. Semantic and phonemic fluencies, cognitive impairment and behavioural dysfunction were also assessed. The mean disease duration of PD was 9.8 years (standard deviation (SD) = 6.13). There were no age (U = 899.5, p = 0.616), gender(chi-square = 0.00, p = 1.00) or literacy (U = 956, p = 0.96) differences between the two groups. A significant difference was observed between the two groups in the action verbal fluency task (U = 406.5, p < 0.01) that was not found in the other fluency tasks. The education level was the only biographical variable that influenced the action (verb) fluency outcomes, irrespective of disease duration. Our findings suggest a correlation between the disease mechanisms in PD and a specific verb deficit, support the validity of the action (verb) fluency as an executive function measure and suggest that this task provides unique information not captured with traditional executive function tasks. PMID:26083889

  3. Management of sexual dysfunction in Parkinson's disease.

    PubMed

    Bronner, Gila; Vodušek, David B

    2011-11-01

    Nonmotor symptoms, among them sexual dysfunction, are common and underrecognized in patients with Parkinson disease; they play a major role in the deterioration of quality of life of patients and their partners. Loss of desire and dissatisfaction with their sexual life is encountered in both genders. Hypersexuality (HS), erectile dysfunction and problems with ejaculation are found in male patients, and loss of lubrication and involuntary urination during sex are found in female patients. Tremor, hypomimia, muscle rigidity, bradykinesia, 'clumsiness' in fine motor control, dyskinesias, hypersalivation and sweating may interfere with sexual function. Optimal dopaminergic treatment should facilitate sexual encounters of the couple. Appropriate counselling diminishes some of the problems (reluctance to engage in sex, problems with ejaculation, lubrication and urinary incontinence). Treatment of erectile dysfunction with sildenafil and apomorphine is evidence based. HS or compulsive sexual behaviour are side effects of dopaminergic therapy, particularly by dopaminergic agonists, and should be treated primarily by diminishing their dose. Neurologists should actively investigate sexual dysfunction in their Parkinsonian patients and offer treatment, optimally within a multidisciplinary team, where a dedicated professional would deal with sexual counselling. PMID:22164191

  4. Sensorimotor adaptation of speech in Parkinson's disease.

    PubMed

    Mollaei, Fatemeh; Shiller, Douglas M; Gracco, Vincent L

    2013-10-01

    The basal ganglia are involved in establishing motor plans for a wide range of behaviors. Parkinson's disease (PD) is a manifestation of basal ganglia dysfunction associated with a deficit in sensorimotor integration and difficulty in acquiring new motor sequences, thereby affecting motor learning. Previous studies of sensorimotor integration and sensorimotor adaptation in PD have focused on limb movements using visual and force-field alterations. Here, we report the results from a sensorimotor adaptation experiment investigating the ability of PD patients to make speech motor adjustments to a constant and predictable auditory feedback manipulation. Participants produced speech while their auditory feedback was altered and maintained in a manner consistent with a change in tongue position. The degree of adaptation was associated with the severity of motor symptoms. The patients with PD exhibited adaptation to the induced sensory error; however, the degree of adaptation was reduced compared with healthy, age-matched control participants. The reduced capacity to adapt to a change in auditory feedback is consistent with reduced gain in the sensorimotor system for speech and with previous studies demonstrating limitations in the adaptation of limb movements after changes in visual feedback among patients with PD. PMID:23861349

  5. Glucocerebrosidase and parkinsonism: lessons to learn.

    PubMed

    Marković, Ivanka; Kresojević, Nikola; Kostić, Vladimir S

    2016-05-01

    Both homo- (causing autosomal-recessive Gaucher's disease; GD) and heterozygous mutations in the glucocerebrosidase gene (GBA) are associated with Parkinson's disease (PD), and represent the most robust known genetic susceptibility factors identified in PD. Since the accumulation of α-synuclein has been considered critical to the pathogenesis of PD among several possible pathways through which glucocerebrosidase (GCase) deficiency may promote the pathogenesis of PD, particular attention was given to the reciprocity with α-synuclein levels, lysosomal dysfunction, endoplasmatic reticulum-Golgi trafficking of GCase, dysregulation of calcium homeostasis and mitochondrial abnormalities. The proportion of PD patients that carry GBA mutations is estimated to be approximately between 5 and 10 %. Individual PD patients with or without GBA mutations cannot be discriminated on clinical or pathological grounds. However, GBA mutation carriers may have slightly earlier age at PD onset, more likely have a positive family history for PD, and more prevalent non-motor symptoms when compared to those patients who are not carriers. Establishing the concept of GBA-related PD promoted a search for the pathogenic mechanisms through which GCase deficiency may influence pathogenesis of PD, suggesting that targeting the GCase-lysosomal pathway might be a rational approach for the development of neuroprotective drugs in PD. PMID:26995357

  6. Fibroblasts from skin biopsies as a tool for biomarker discovery in Parkinson׳s disease.

    PubMed

    Mastroberardino, Pier Giorgio; Ambrosi, Giulia; Blandini, Fabio; Milanese, Chiara; Sepe, Sara

    2014-10-01

    Parkinson׳s disease (PD) is a complex disease and the current interest and focus of scientific research is both investigating the variety of causes that underlie PD pathogenesis, and identifying reliable biomarkers to diagnose and monitor the progression of pathology. Investigation on pathogenic mechanisms in peripheral cells, such as fibroblasts derived from patients with sporadic PD and age/gender matched controls, might generate deeper understanding of the deficits affecting dopaminergic neurons and, possibly, new tools applicable to clinical practice. The chronic and slow progressing nature of PD may result from subtle yet persistent alterations in biological mechanisms, which might be undetectable in basal, unchallenged conditions. Unlike body fluids, dermal fibroblasts can be exposed to different challenges while in culture and can therefore generate information about the dynamic cellular responses to exogenous stressors. These studies may ultimately generate indicators highlighting the biological defects intrinsic to PD. In fact, fibroblasts from idiopathic PD patients' exhibit deficits typically sustaining the neurodegenerative process of PD, such as increased susceptibility to rotenone as well as deficits in protein homeostasis and mitochondrial bioenergetics Fibroblasts therefore represent a powerful and minimally invasive tool to investigate PD pathogenic mechanisms, which might translate into considerable advances in clinical management of the disease. PMID:26461279

  7. Translational research for Parkinson׳s disease: The value of pre-clinical primate models.

    PubMed

    Aron Badin, Romina; Vadori, Marta; Cozzi, Emanuele; Hantraye, Philippe

    2015-07-15

    Animal models have been highly questioned for their ability to predict the efficacy of different therapeutic strategies for neurodegenerative diseases. The increasing number of phase I/II clinical trials that fail to proceed to further stages of drug development has discredited the pertinence of such investigations. However, critical analysis of the data has often revealed errors and partially explained the lack of efficacy, opening the way to a refinement in designing pre-clinical studies. In parallel, many promising methods of drug delivery to the brain such as gene therapy or cell therapy have considerably advanced thanks to the clinical failures in the past 10 years. As methodological advances appear and knowledge becomes available, scientists will be faced with the choice of how to test new strategies or re-test old ones. With the hardening of social views and legislation regarding animal experimentation, there is increasing pressure to find alternative methods of assessment that predict efficacy (such as computational based models), or to perform efficacy trials directly in patients and only safety assays in animals. In this review we will focus on Parkinson׳s disease and on the impact of a body of data issued from NHP studies. We will attempt to critically examine the advantages and limitations of various approaches from the perspective of the animal model used to address specific questions. PMID:25841877

  8. Pisa syndrome in Parkinson's disease and parkinsonism: clinical features, pathophysiology, and treatment.

    PubMed

    Barone, Paolo; Santangelo, Gabriella; Amboni, Marianna; Pellecchia, Maria Teresa; Vitale, Carmine

    2016-09-01

    Pisa syndrome is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. It is a frequent and often disabling complication of Parkinson's disease, and has also been described in several atypical forms of parkinsonism and in neurodegenerative and psychiatric disorders after drug exposure and surgical procedures. Although no consistent diagnostic criteria for Pisa syndrome are available, most investigations have adopted an arbitrary cutoff of at least 10° of lateral flexion for the diagnosis of the syndrome. Pathophysiological mechanisms underlying Pisa syndrome have not been fully explained. One hypothesis emphasises central mechanisms, whereby Pisa syndrome is thought to be caused by alterations in sensory-motor integration pathways; by contrast, a peripheral hypothesis emphasises the role of anatomical changes in the musculoskeletal system. Furthermore, several drugs are reported to induce Pisa syndrome, including antiparkinsonian drugs. As Pisa syndrome might be reversible, clinicians need to be able to recognise this condition early to enable prompt management. Nevertheless, further research is needed to determine optimum treatment strategies. PMID:27571158

  9. Mitochondrial DNA sequence analysis of four Alzheimer`s and Parkinson`s disease patients

    SciTech Connect

    Brown, M.D.; Shoffner, J.M.; Wallace, D.C.

    1996-01-22

    The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer`s disease (AD) exhibiting AD plus Parkinson`s disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA{sup Gln} gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients or 905 controls. In the second AD + PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD + PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber`s hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a casual role for these base substitutions in neurodegenerative disease. 68 refs., 2 tabs.

  10. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    PubMed

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD. PMID:26618044

  11. Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson's disease.

    PubMed

    Ling, Helen; Massey, Luke A; Lees, Andrew J; Brown, Peter; Day, Brian L

    2012-04-01

    Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease defines bradykinesia as 'slowness of initiation with progressive reduction in speed and amplitude of repetitive action'. Although progressive supranuclear palsy is considered an atypical parkinsonian syndrome, it is not known whether patients with progressive supranuclear palsy have criteria-defined bradykinesia. This study objectively assessed repetitive finger tap performance and handwriting in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n = 9) and healthy age- and gender-matched controls (n = 16). The motion of the hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb tapping trials. The main finding was hypokinesia without decrement in patients with progressive supranuclear palsy, which differed from the finger tap pattern in Parkinson's disease. Average finger separation amplitude in progressive supranuclear palsy was less than half of that in controls and Parkinson's disease (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was computed by linear regression. The average amplitude slope in progressive supranuclear palsy was nearly zero (0.01°/cycle) indicating a lack of decrement, which differed from the negative slope in patients with Parkinson's disease OFF levodopa (-0.20°/cycle, P = 0.002). 'Hypokinesia', defined as <50% of control group's mean amplitude, combined with 'absence of decrement', defined as mean positive amplitude slope, were identified in 87% of finger tap trials in the progressive supranuclear palsy group and only 12% in the Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the mean amplitude was not correlated with disease duration or other clinimetric scores. In Parkinson's disease, finger tap pattern was compatible with criteria-defined bradykinesia

  12. High-dose thiamine as initial treatment for Parkinson's disease

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Compagnoni, Laura; Colangeli, Marco

    2013-01-01

    Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23986125

  13. Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders

    PubMed Central

    Scholz, Sonja W.; Bras, Jose

    2015-01-01

    Atypical parkinsonism syndromes, such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, are neurodegenerative diseases with complex clinical and pathological features. Heterogeneity in clinical presentations, possible secondary determinants as well as mimic syndromes pose a major challenge to accurately diagnose patients suffering from these devastating conditions. Over the last two decades, significant advancements in genomic technologies have provided us with increasing insights into the molecular pathogenesis of atypical parkinsonism and their intriguing relationships to related neurodegenerative diseases, fueling new hopes to incorporate molecular knowledge into our diagnostic, prognostic and therapeutic approaches towards managing these conditions. In this review article, we summarize the current understanding of genetic mechanisms implicated in atypical parkinsonism syndromes. We further highlight mimic syndromes relevant to differential considerations and possible future directions. PMID:26501269

  14. Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders.

    PubMed

    Scholz, Sonja W; Bras, Jose

    2015-01-01

    Atypical parkinsonism syndromes, such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, are neurodegenerative diseases with complex clinical and pathological features. Heterogeneity in clinical presentations, possible secondary determinants as well as mimic syndromes pose a major challenge to accurately diagnose patients suffering from these devastating conditions. Over the last two decades, significant advancements in genomic technologies have provided us with increasing insights into the molecular pathogenesis of atypical parkinsonism and their intriguing relationships to related neurodegenerative diseases, fueling new hopes to incorporate molecular knowledge into our diagnostic, prognostic and therapeutic approaches towards managing these conditions. In this review article, we summarize the current understanding of genetic mechanisms implicated in atypical parkinsonism syndromes. We further highlight mimic syndromes relevant to differential considerations and possible future directions. PMID:26501269

  15. Into the groove: can rhythm influence Parkinson's disease?

    PubMed

    Nombela, Cristina; Hughes, Laura E; Owen, Adrian M; Grahn, Jessica A

    2013-12-01

    Previous research has noted that music can improve gait in several pathological conditions, including Parkinson's disease, Huntington's disease and stroke. Current research into auditory-motor interactions and the neural bases of musical rhythm perception has provided important insights for developing potential movement therapies. Specifically, neuroimaging studies show that rhythm perception activates structures within key motor networks, such as premotor and supplementary motor areas, basal ganglia and the cerebellum - many of which are compromised to varying degrees in Parkinson's disease. It thus seems likely that automatic engagement of motor areas during rhythm perception may be the connecting link between music and motor improvements in Parkinson's disease. This review seeks to describe the link, address core questions about its underlying mechanisms, and examine whether it can be utilized as a compensatory mechanism. PMID:24012774

  16. [Parkinson's disease due to laboral exposition to paraquat].

    PubMed

    León-Verastegui, Angel Gilberto

    2012-01-01

    Parkinson's disease is considered a neurodegenerative disorder, which involves environmental factors in the etiology of the disease. Such as chemical agents with neuromolecular effect among which is the MPTP (1-methyl-4-phenyl-1, 2, 3, 6 tetra-hydropyridine), MPP (1-methyl-4-phenyl hypyridinium), paraquat, the latter used as a herbicide in the agricultural fields of our country. It has been documented in epidemiological and experimental studies the association of occupational exposure to paraquat and Parkinson's disease. The aim of this paper is to describe a clinical case of occupational medicine in Parkinson's disease in occupationally exposed workers to paraquat, elevating the importance of medical history work, which was the key to the clinical case study. PMID:23331754

  17. Valproate-Associated Parkinsonism: A Critical Review of the Literature.

    PubMed

    Brugger, Florian; Bhatia, Kailash P; Besag, Frank M C

    2016-06-01

    Valproate was first approved as an antiepileptic drug in 1962 and has since also become established as a mood stabiliser and as prophylaxis for migraine. In 1979, Lautin published the first description of a valproate-associated extrapyramidal syndrome. Many cases of valproate-associated parkinsonism have subsequently been published, but uncertainties remain concerning its prevalence, risk factors and prognosis. The aim of this paper is to provide a critical review of the existing literature on valproate-associated parkinsonism and to discuss possible mechanisms. Literature databases were searched systematically: we identified a total of 116 patients with valproate-associated parkinsonism published in case reports, case series and systematic analyses. Prevalence rates ranged widely, between 1.4 and 75 % of patients taking valproate. There was great heterogeneity with regard to clinical presentation, age of onset, valproate dose, concomitant conditions and imaging findings. In all patients apart from three, valproate plasma concentrations were within or even below the recommended reference range when the parkinsonism occurred. Parkinsonism was reversible in the majority of patients, although recovery was often prolonged and sometimes incomplete. A dopaminergic deficit was confirmed in three of six patients investigated with dopamine transporter imaging. Seven of 14 patients who were treated with dopaminergic medication had a good response. The quality of the evidence was assessed and probability of causation was examined using the Naranjo score, which ranged from 0 to 7 (median: 5.0). Several pathophysiological mechanisms, including altered gene expression and neurotransmitter signalling, enhanced neurodegeneration or unmasking subclinical dopaminergic degeneration, could theoretically lead to valproate-associated parkinsonism. Further studies are warranted to elucidate this entity and its underlying pathophysiology. PMID:27255404

  18. Quantitative Motor Performance and Sleep Benefit in Parkinson Disease

    PubMed Central

    van Gilst, Merel M.; van Mierlo, Petra; Bloem, Bastiaan R.; Overeem, Sebastiaan

    2015-01-01

    Study Objectives: Many people with Parkinson disease experience “sleep benefit”: temporarily improved mobility upon awakening. Here we used quantitative motor tasks to assess the influence of sleep on motor functioning in Parkinson disease. Design: Eighteen Parkinson patients with and 20 without subjective sleep benefit and 20 healthy controls participated. Before and directly after a regular night sleep and an afternoon nap, subjects performed the timed pegboard dexterity task and quantified finger tapping task. Subjective ratings of motor functioning and mood/vigilange were included. Sleep was monitored using polysomnography. Results: On both tasks, patients were overall slower than healthy controls (night: F2,55 = 16.938, P < 0.001; nap: F2,55 = 15.331, P < 0.001). On the pegboard task, there was a small overall effect of night sleep (F1,55 = 9.695, P = 0.003); both patients and controls were on average slightly slower in the morning. However, in both tasks there was no sleep*group interaction for nighttime sleep nor for afternoon nap. There was a modest correlation between the score on the pegboard task and self-rated motor symptoms among patients (rho = 0.233, P = 0.004). No correlations in task performance and mood/vigilance or sleep time/efficiency were found. Conclusions: A positive effect of sleep on motor function is commonly reported by Parkinson patients. Here we show that the subjective experience of sleep benefit is not paralleled by an actual improvement in motor functioning. Sleep benefit therefore appears to be a subjective phenomenon and not a Parkinson-specific reduction in symptoms. Citation: van Gilst MM, van Mierlo P, Bloem BR, Overeem S. Quantitative Motor Performance and Sleep Benefit in Parkinson Disease. SLEEP 2015;38(10):1567–1573. PMID:25902811

  19. Recent progress of imaging agents for Parkinson's disease.

    PubMed

    Wu, Xiaoai; Cai, Huawei; Ge, Ran; Li, Lin; Jia, Zhiyun

    2014-12-01

    Parkinson's disease (PD) is a common progressive, neurodegenerative brain disease that is promoted by mitochondrial dysfunction, oxidative stress, protein aggregation and proteasome dysfunction in the brain. Compared with computer tomography (CT) or magnetic resonance imaging (MRI), non-invasive nuclear radiopharmaceuticals have great significance for the early diagnosis of PD due to their high sensitivity and specificity in atypical and preclinical cases. Based on the development of coordination chemistry and chelator design, radionuclides may be delivered to lesions by attaching to PD-related transporters and receptors, such as dopamine, serotonin, and others. In this review, we comprehensively detailed the current achievements in radionuclide imaging in Parkinson's disease. PMID:25977680

  20. Genetics of Parkinson disease: paradigm shifts and future prospects.

    PubMed

    Farrer, Matthew James

    2006-04-01

    Parkinson disease is a complex, multifactorial neurodegenerative disease. Although a heritable basis was originally thought unlikely, recent studies have implicated several genes in its pathogenesis, and molecular findings now allow accurate diagnosis and challenge past criteria for defining Parkinson disease. Most importantly, genetic insights provide the rationale for new strategies for prevention or therapy, and have led to animal models of disease in which these strategies can be tested. Neuroprotective therapies can now be designed to slow or halt disease progression in affected subjects and asymptomatic carriers. PMID:16543934

  1. Oral rehabilitation of a Parkinson's patient: A case report.

    PubMed

    Singh, Yashpal; Saini, Monika; Garg, Neha

    2013-04-16

    Parkinson's disease is an idiopathic disorder of the central nervous system, characterized by resting tremors, muscular rigidity, slow and decreased movements. Oral rehabilitation of these patients requires special care, especially in those cases where the patient's socioeconomic status is not good and patient cannot come several times for fabrication of a complete denture. This clinical report presents a case of a Parkinson's patient who was completely rehabilitated in 3 appointments using special techniques. Border molding, final impression and jaw relation procedures were done in one appointment by using a custom tray with detachable handles and occlusal rims. PMID:24303468

  2. Transient dynamics in motor control of patients with Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Beuter, Anne; Labrie, Christiane; Vasilakos, Konstantinon

    1991-10-01

    Experimental observations of movement disorders including tremor and voluntary microdisplacements recorded in patients with Parkinson's disease (PD) during a simple visuomotor tracking task are analyzed. The performance of patients with PD having a very large amplitude tremor is characterized either by the intermittent appearance of transient dynamics or by the presence of sudden transitions in the amplitude or frequency of the signal. The need to develop new tools to characterize changes in dynamics (i.e., transitions) and to redefine neurological degeneration, such as Parkinson's disease, in terms of qualitative changes in oscillatory behaviors is emphasized.

  3. Arachnophobia alleviated by subthalamic nucleus stimulation for Parkinson's disease.

    PubMed

    Allert, Niels; Gippert, Sabrina M; Sajonz, Bastian E A; Nelles, Christoph; Bewernick, Bettina; Schlaepfer, Thomas E; Coenen, Volker A

    2016-06-01

    We report on a Parkinson patient with motor fluctuations and dyskinesias in whom deep brain stimulation (DBS) of the subthalamic nucleus (STN) not only improved motor symptoms but also pre-existing arachnophobia. Arachnophobia had been unchanged by the course of Parkinson's disease but rapidly improved with STN-DBS. Both, motor effects and the improvement of arachnophobia were stable during 2 years follow-up. To our knowledge this is the first report on STN stimulation effects on a specific phobia. PMID:27198699

  4. The Demise of Poskanzer and Schwab's Influenza Theory on the Pathogenesis of Parkinson's Disease

    PubMed Central

    Okun, Michael S.

    2013-01-01

    In 1961, David C. Poskanzer and Robert S. Schwab presented a paper, “Studies in the epidemiology of Parkinson's disease predicting its disappearance as a major clinical entity by 1980.” This paper introduced the hypothesis that Parkinson's disease was derived from a single aetiology, the influenza virus. We review the original Poskanzer and Schwab hypothesis that Parkinson's disease was based on the association between the 1918-19 influenza epidemic and the later observation of Parkinsonism in some influenza sufferers. We also further explore the prediction that Parkinson's disease would totally disappear as an entity once original influenza victims were all deceased. Current research has revealed that there are many potential causes and factors important in the occurrence of Parkinson's disease, postencephalitic Parkinsonism, and encephalitis lethargica. Poskanzer and Schwab presented a novel hypothesis; however, it was proven false by a combination of research and time. PMID:23853734

  5. Nocturnal manifestations of atypical and vascular parkinsonism: how do they differ from Parkinson's disease?

    PubMed

    Bhidayasiri, Roongroj; Jitkritsadakul, Onanong; Petchrutchatachart, Sitthi; Kaewwilai, Lalita; Panyakaew, Pattamon; Boonrod, Nonglak; Colosimo, Carlo

    2014-08-01

    While nocturnal disturbances of Parkinson's disease (PD) are increasingly recognized as being part of a continuum that includes daytime manifestations, there is still little analysis in the medical literature that assesses these complex phenomena in patients with atypical (AP) and vascular parkinsonisms (VP). The objective of our study was to determine the prevalence of these disturbances in patients with AP and VP and to determine the range of nighttime symptoms that occur compared with those in patients with PD. This comparison was done using a semi-structured interview and self-rated questionnaires in 63 AP and VP patients (PSP 24, MSA 24, CBD 5, and VP 10), and 208 PD patients. 61 AP and VP patients (96.8%) and 201 PD patients (96.6%) reported at least one nocturnal symptom with a score of less than 6 on the Modified Parkinson's Disease Sleep Scale (MPDSS). Nocturnal akinesia, as measured on the Nocturnal Akinesia, Dystonia, and Cramp Score, was found to be significantly greater in patients with PSP (p = 0.006), MSA (p = 0.002), and CBD (p = 0.012) than PD patients, but not VP patients (p = 0.428). Like those with PD, patients with AP and VP identified the problem of getting up at night to urinate (MPDSS item 8) as being the most frequent and troublesome nocturnal symptom. MSA and PSP patients reported more frequent (p = 0.001) and troublesome (p < 0.001) urinary incontinence (MPDSS item 9) than PD patients and MSA patients had more severe problems with unexpectedly falling asleep during the day (MPDSS item 15) than PD patients (p = 0.003). In summary, our study determined that nocturnal manifestations are commonly experienced by patients with AP and VP and highlighted specific nocturnal symptoms, which are more prevalent and troublesome in certain AP syndromes. The concept of 24-h control of symptoms should not be limited to only PD and we recommend that all who are involved in the care of AP and VP patients should realize that many nocturnal symptoms are

  6. Deep Brain Stimulation for Parkinson Disease

    PubMed Central

    Bronstein, Jeff M.; Tagliati, Michele; Alterman, Ron L.; Lozano, Andres M.; Volkmann, Jens; Stefani, Alessandro; Horak, Fay B.; Okun, Michael S.; Foote, Kelly D.; Krack, Paul; Pahwa, Rajesh; Henderson, Jaimie M.; Hariz, Marwan I.; Bakay, Roy A.; Rezai, Ali; Marks, William J.; Moro, Elena; Vitek, Jerrold L.; Weaver, Frances M.; Gross, Robert E.; DeLong, Mahlon R.

    2015-01-01

    Objective To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). Data Sources and Study Selection An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. Data Extraction and Synthesis A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. Conclusions (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients. PMID:20937936

  7. MAO-inhibitors in Parkinson's Disease

    PubMed Central

    Laux, Gerd

    2011-01-01

    Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD. PMID:22110357

  8. Depression and subsequent risk of Parkinson disease

    PubMed Central

    Gustafsson, Helena; Nordström, Anna

    2015-01-01

    Objective: To investigate the long-term risk of Parkinson disease (PD) after depression and evaluate potential confounding by shared susceptibility to the 2 diagnoses. Methods: The nationwide study cohort included 140,688 cases of depression, matched 1:3 using a nested case-control design to evaluate temporal aspects of study parameters (total, n = 562,631). Potential familial coaggregation of the 2 diagnoses was investigated in a subcohort of 540,811 sibling pairs. Associations were investigated using multivariable adjusted statistical models. Results: During a median follow-up period of 6.8 (range, 0–26.0) years, 3,260 individuals in the cohort were diagnosed with PD. The multivariable adjusted odds ratio (OR) for PD was 3.2 (95% confidence interval [CI], 2.5–4.1) within the first year of depression, decreasing to 1.5 (95% CI, 1.1–2.0) after 15 to 25 years. Among participants with depression, recurrent hospitalization was an independent risk factor for PD (OR, 1.4; 95% CI, 1.1–1.9 for ≥5 vs 1 hospitalization). In family analyses, siblings' depression was not significantly associated with PD risk in index persons (OR, 1.1; 95% CI, 0.9–1.4). Conclusions: The time-dependent effect, dose-response pattern for recurrent depression, and lack of evidence for coaggregation among siblings all indicate a direct association between depression and subsequent PD. Given that the association was significant for a follow-up period of more than 2 decades, depression may be a very early prodromal symptom of PD, or a causal risk factor. PMID:25995056

  9. Submovements during pointing movements in Parkinson's disease.

    PubMed

    Dounskaia, Natalia; Fradet, Laetitia; Lee, Gyusung; Leis, Berta C; Adler, Charles H

    2009-03-01

    Velocity irregularities frequently observed during deceleration of arm movements have usually been interpreted as corrective submovements that improve motion accuracy. This hypothesis is re-examined here in application to movements of Parkinson's disease (PD) patients in which submovements are specifically frequent. Pointing movements in patients and age-matched controls to large and small targets in three movement modes were studied. The modes were discrete (stop on the target), continuous (reverse on the target), and passing (stop after crossing the target). Two types of submovements were distinguished, gross and fine. In both groups, gross submovements were more frequent during the discrete and passing than continuous mode, specifically for large targets. This suggested that gross submovements were fluctuations accompanying motion termination (stabilization at the target) that was included in discrete and passing but not continuous movements. Gross submovements were specifically frequent in patients, suggesting that PD causes deficiency in smooth motion termination. Although in both groups fine submovements were more frequent for small than large targets, this relation was also observed in passing movements after crossing the target, i.e., when no corrections were needed. This result, together with higher jerk of the entire trajectory found for smaller targets, indicates that fine submovements may also be not corrective adjustments but rather velocity fluctuations emerging due to low speed of movements to small targets. This interpretation is consistent with the recognized inability of PD patients to promptly change generated force as well as to quickly re-plan current motion. The results suggest a need to re-examine the traditional interpretation of submovements in PD and the related theory that the production of iterative submovements is a strategy used by patients to compensate for a decreased initial force pulse. PMID:19048238

  10. Neurobehavioral functioning of persons with Parkinson's disease.

    PubMed

    Mathias, J L

    2003-01-01

    This study examines the neurobehavioral functioning of persons with Parkinson's disease (PD) using the Neuropsychology Behavior and Affect Profile (NBAP), a self-report version of the Neurobehavioral Rating Scale (NRS-Revised), and the Dysexecutive Questionnaire (DEX). In the absence of existing data, the psychometric properties of these measures were assessed prior to examining neurobehavioral functioning. Self- and observer report versions of the NBAP, NRS-Revised, and DEX were administered to a group of 30 persons with PD and 30 matched controls. Reliability analyses revealed that, although the total scores from these measures provided internally reliable assessments of neurobehavioral functioning, the sub-scale scores of the NBAP demonstrated lower reliability. In addition, the 3 measures of neurobehavioral functioning showed moderate to high correlations with one another and with measures of disease severity. When the PD and control groups were compared on measures of current neurobehavioral functioning, the PD group was found to exhibit problems on the NRS-Revised. Since the onset of their disease, the PD group showed increasing levels of depression, inappropriate behavior, and a reduced ability to follow the subtleties of communication as measured by the NBAP. There was good agreement between self- and observer-reports of neurobehavioral functioning, suggesting that problems with insight did not affect patients' reports of symptomatology. Overall, the findings indicate the emergence of a number of neurobehavioral problems in the early stages of PD that are likely to adversely affect the social interactions of persons with PD. When combined with the motor and cognitive effects of PD, these problems may lead to social isolation. PMID:12788680

  11. Genomic and pharmacogenomic biomarkers of Parkinson's disease.

    PubMed

    Alonso-Navarro, Hortensia; Jimenez-Jimenez, Felix Javier; Garcia-Martin, Elena; Agundez, Jose A G

    2014-02-01

    The relative role of genetic and environmental factors in the pathogenesis of Parkinson's disease (PD) has been the matter of investigation and debate, especially in the last 30 years. The possible interaction between genetic and environmental factors led to a great number of association studies between single nucleotide polymorphisms (SNPs) of many candidate genes and PD risk. In this study we summarized and critically reviewed the results of studies published on this issue, with especial reference to those reported in the last 5 years. Many studies provided conflicting findings and, when positive associations were identified, associations were weak. Polymorphisms related with activation or detoxification of drugs and xenobiotics, such as CYP1A1, CYP1A2, CYP19A1, CYP1B1, CYP2C9, CYP2C19, CYP2E1, CYP2D6, NAT2, GSTM1, GSTM3, GSTO1, GSTP1, PON1, PON2, ABCB1 and ADH genes have not been demonstrated convincingly a definitive association with the risk of developing PD. Nor did polymorphisms in genes related to dopamine or serotonin DRD, DAT, TH, DDC, DBH, MAO, COMT, SLC6A4, MTR, MTHFR, oxidative stress NOQ1, NOQ2, mEPHX, HFE, GPX, CAT, mnSOD, HFE, HO-1, HO-2, NFE2L2, KEAP1, inflammatory processes, ILs, TNF, ACT, NOS, HNMT, ABP1, HRHs, trophic and growth factors BDNF, FGF, or mitochondrial metabolism and function. In addition we analyzed other putative relations and genes associated with monogenic familial PD.Taking together the results of candidate gene association studies and genome wide association studies, only some SNPs of the MAPT, SNCA, HLA and GBA genes seem to be the most likely associated with PD risk. PMID:24694231

  12. Methylphenidate : a treatment for Parkinson's disease?

    PubMed

    Devos, David; Moreau, Caroline; Delval, Arnaud; Dujardin, Kathy; Defebvre, Luc; Bordet, Regis

    2013-01-01

    Parkinson's disease (PD) affects about 1 % of the population over the age of 60 years and is characterized by a combination of rest tremor, bradykinesia, rigidity, postural instability, stooped posture and freezing of gait (FoG). However, the clinical spectrum also spans a wide range of non-motor symptoms, such as depression, apathy, cognitive disorders, sleepiness, fatigue and pain. Given that the loss of dopamine in the striatum is the primary pathochemical hallmark in PD, pharmacological treatment of the disease has focused on restoring dopaminergic neurotransmission. The currently licensed dopaminergic treatments for PD modulate all the key steps in the dopamine transmission except the most powerful determinant of extracellular dopamine concentrations: the presynaptic dopamine transporter (DaT). Methylphenidate is a CNS stimulant that blocks the DaT and the noradrenaline (norepinephrine) transporter in the striatum and the prefrontal cortex in particular. Here, we report on and discuss the main open-label studies and randomized controlled trials on the effect of methylphenidate on severe gait disorders (e.g. the FoG) and non-motor symptoms in advanced PD. The various pharmacodynamic effects of methylphenidate mean that the drug may have significant value in the treatment of PD. However, there is a lack of randomized controlled trials in this field. Furthermore, more rigorous selection of the types and doses of the associated dopaminergic treatments is required because these parameters may profoundly influence the mechanisms of action of methylphenidate and the clinical outcomes. Pharmacogenetic tools could be of use in better defining study patients as a function of their dopaminergic metabolism and drug responsiveness. PMID:23160937

  13. Olfaction in Parkinson's disease and related disorders

    PubMed Central

    Doty, Richard L.

    2012-01-01

    Olfactory dysfunction is an early ‘pre-clinical’ sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology,or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances. PMID:22192366

  14. Familial aggregation of Parkinson disease in Utah

    PubMed Central

    Savica, Rodolfo; Pulst, Stefan

    2016-01-01

    Objective: To describe clustering of death from Parkinson disease (PD) in relatives in a large US study. Methods: We analyzed the Utah Population Database resource, which includes genealogy data of more than 2.7 million individuals linked to 519,061 individuals with a Utah death certificate (DC). We identified individuals whose DC included PD as a cause of death using ICD coding. In those individuals whose Utah DC listed PD as a cause of death, the relative risk (RR) of death with PD was determined among close and distant relatives using sex-, birth year–, and birthplace-specific rates. Results: We identified 4,031 individuals whose DC indicated PD. Among 18,127 first-degree relatives of probands with a Utah DC, the RR of death with PD was significantly increased (RR = 1.82, 95% confidence interval [CI] 1.61–2.04). The RR of death with PD was also significantly increased among 40,546 second-degree relatives with a Utah DC (RR = 1.44, 95% CI 1.29–1.60) and among 93,398 third-degree relatives with a Utah DC (RR = 1.10, 95% CI 1.03–1.18). Conclusions: Significant evidence for excess familial clustering was observed for PD deaths. The excess familial clustering and the significantly elevated RRs for PD among close and distant relatives strongly support a genetic contribution to PD mortality. These results confirm and expand the results of previous studies of PD by quantifying the risk of PD death among more distant relatives. PMID:27123483

  15. [A 73-year-old woman with familial Parkinson's disease].

    PubMed

    Takanashi, M; Urabe, T; Ohta, S; Hamano, Y; Mori, H; Shirai, T; Kondo, T; Mizuno, Y

    1999-12-01

    We report a 73-year-old Japanese woman with familial Parkinson's disease. The patient was well until her 67 years of the age, when she noted rest tremor in her right hand. Soon after her gait became short stepped. She visited our clinic on October 6, 1992 when she was 68 years old. She was alert and well oriented without dementia. She showed masked face, small voice, small stepped gait, retropulsion, resting tremor in her right hand, rigidity in the neck, and bradykinesia. She was treated with 400 mg/day of levodopa-carbidopa, which improved her symptoms, however, she developed wearing off phenomenon 3 years after the initiation of levodopa treatment. On August 26, 1998, she developed abdominal pain, diarrhea, and vomiting. She was admitted to another hospital, where abdominal plain x-ray revealed an evidence of intestinal obstruction (ileus). She was treated with nasogastric suction and intravenous fluid. Her condition did not improve and she was transferred to our hospital on August 29, 1998. Her family history revealed no consanguineous marriage. She had two elder brothers and three elder sisters. One of her brothers had been diagnosed as Parkinson's disease. Her husband also suffered from Parkinson's disease, however, her parents apparently did not have Parkinson's disease. On admission, she appeared to be drowsy. Her blood pressure was 102/70 mmHg, body temperature 36.2 degrees C. The lungs were clear and no cardiac murmur was present. Abdomen was flat and bowel sound was audible. No abnormal mass was palpable. Neurologic examination revealed mild consciousness disturbance, masked face, and small voice. No motor paralysis was noted. Muscle tone was hypotonic. No abnormal involuntary movement was noted. Abnormal laboratory findings on admission were as follows; WBC 11,300/microliter, amylase 1,373 IU/l, CK 446 IU/l, BUN 50 mg/dl, creatinine 1.17 mg/dl, CRP 22.7 mg/ dl, Na 134 mEq/l, K 3.1 mEq/l, and Cl 81 mEq/l. A chest x-ray film revealed pneumonic shadows in

  16. Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease: ICICLE-PD study.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; Firbank, Michael J; Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Owen, Adrian M; Khoo, Tien K; Brooks, David J; Rowe, James B; Barker, Roger A; Burn, David J; O'Brien, John T

    2015-10-01

    Mild cognitive impairment in Parkinson's disease is associated with progression to dementia (Parkinson's disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson's disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects with newly diagnosed idiopathic Parkinson's disease and 37 healthy matched controls had serial 3 T structural magnetic resonance imaging scans with clinical and neuropsychological assessments at baseline, which were repeated after 18 months. The Movement Disorder Society Task Force criteria were used to classify the Parkinson's disease subjects into Parkinson's disease with mild cognitive impairment (n = 39) and Parkinson's disease with no cognitive impairment (n = 66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. At baseline, cases with Parkinson's disease with mild cognitive impairment demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and subjects with Parkinson's disease with no cognitive impairment. Regional cortical thickness at baseline was correlated with global cognition in the combined Parkinson's disease cohort. Over 18 months, patients with Parkinson's disease with mild cognitive impairment demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to those with Parkinson's disease and no cognitive impairment and healthy controls, whereas subjects with Parkinson's disease and no cognitive impairment showed more severe frontal cortical thinning compared to healthy controls. At baseline, Parkinson's disease with no cognitive impairment

  17. The medical treatment of Parkinson disease from James Parkinson to George Cotzias.

    PubMed

    Fahn, Stanley

    2015-01-01

    It took exactly 150 years since James Parkinson's description in 1817 of the illness bearing his name until the development of effective therapy for this disorder, namely, the introduction of high-dosage levodopa by George Cotzias in 1967. During the first 50 years, no effective therapy was available, but neurologists reported using different agents, including metals. Then, around 1867, Charcot found solanaceous alkaloids to be somewhat helpful, and these became the accepted and popular therapy for the next 75 years. When basic scientists discovered that these alkaloids had central antimuscarinic activity, pharmaceutical chemists developed synthetic chemical agents that were equally effective, with possibly less adverse effects, and around 1950 these synthetic drugs became the standard medical therapy for Parkinson's disease (PD). The link between dopamine and PD did not take place until 1957, 140 years after Parkinson's Essay. The clue came from research on reserpine, a drug derived from the Rauwolfia plant that caused a sedative effect, now recognized as a drug-induced parkinsonian state. Initial investigations revealed that reserpine caused the release and depletion of serotonin stores in the brain. With that knowledge, Arvid Carlsson, a young pharmacologist in Sweden, decided to explore the possibility that reserpine might also affect brain catecholamines. In his now famous, elegant, and simple experiment, he showed that injecting l-dopa, the precursor of catecholamines, alleviated the reserpine-induced parkinsonian state in animals, whereas the precursor of serotonin failed to do so. Carlsson then developed a highly sensitive assay to measure dopamine, and his lab found that dopamine is selectively present in high concentrations in the striatum and that administered l-dopa could restore the dopamine depleted by reserpine. Carlsson postulated that all these findings implicate dopamine in motor disorders. Oleh Hornykiewicz, a young pharmacologist in Vienna, on

  18. CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

    PubMed

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S; Toledo, Jon B; Weintraub, Daniel; Galasko, Douglas R; Irwin, David J; Van Deerlin, Vivianna; Chen-Plotkin, Alice S; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W; Chowdhury, Sohini; Trojanowski, John Q; Shaw, Leslie M

    2016-06-01

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

  19. Finger tapping analysis in patients with Parkinson's disease and atypical parkinsonism.

    PubMed

    Djurić-Jovičić, Milica; Petrović, Igor; Ječmenica-Lukić, Milica; Radovanović, Saša; Dragašević-Mišković, Nataša; Belić, Minja; Miler-Jerković, Vera; Popović, Mirjana B; Kostić, Vladimir S

    2016-08-01

    The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinson's disease (PD), progressive supranuclear palsy-Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n=13), PSP-R (n=15), and MSA-P (n=14) patients and matched healthy controls (HC; n=14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of -0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (-0.21°/cycle, p=0.032), and particularly from PD (-0.56°/cycle, p=0.001), and MSA-P patients (-1.48°/cycle, p=0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (pmsa-pd=0.726, pmsa-psp=0.363, ppsp-pd=0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism. PMID:27343040

  20. α-Synuclein inclusions in the skin of Parkinson's disease and parkinsonism

    PubMed Central

    Rodríguez-Leyva, Ildefonso; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E; Rentería-Palomo, Ana Arely; Hernandez-Rodriguez, Héctor Gerardo; Valdés-Rodríguez, Rodrigo; Fuentes-Ahumada, Cornelia; Torres-Álvarez, Bertha; Sepúlveda-Saavedra, Julio; Soto-Domínguez, Adolfo; Santoyo, Martha E; Rodriguez-Moreno, José Ildefonso; Castanedo-Cázares, Juan Pablo

    2014-01-01

    Objective The presence in the brain of α-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of α-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. Our goals were, first, to demonstrate the presence of α-synuclein inclusions in the skin and, second, to detect quantitative differences between patients with PD and atypical parkinsonism (AP). Methods Skin biopsies were taken from 67 patients and 20 controls. The biopsies underwent immunohistochemistry (IHC) and immunofluorescence (IF) testing for α-synuclein, whereupon its presence was quantified as the percentage of positive cells. Patients were divided into those with PD and those with AP. AP patients included AP with neurodegenerative disease (proteinopathies) and secondary AP. Results Sixty-seven patients (34 with PD) and 20 controls were recruited. In the PD group, α-synuclein was detected in 58% of the cells in the spinous cell layer (SCL), 62% in the pilosebaceous unit (PSU), and 58% in the eccrine glands (EG). The AP-proteinopathies group showed 7%, 7%, and 0% expression of α-synuclein, respectively. No expression was found in the skin of the control group. Conclusions The expression of α-synuclein in the skin was relatively high in the PD group, scarce in AP, and null for the individuals in the control group. While these findings require further confirmation, this minimally invasive technique may aid in the improvement of the accuracy of PD diagnoses. PMID:25356418

  1. Throat clicking as the initial symptom of Parkinson's disease.

    PubMed

    Iyer, Sanjay S; Morgan, John C; Glover, Andrea L; Sethi, Kapil D

    2005-10-01

    The presenting manifestations of Parkinson's disease (PD) are variable, but a majority of patients note tremor as the initial symptom. Others complain of slowing of movements, loss of dexterity, fatigue, or changes in handwriting as initial symptoms. We describe a patient who developed an unusual clicking sound emanating from his throat as the initial manifestation of PD. PMID:16001408

  2. Impaired Awareness of Movement Disorders in Parkinson's Disease

    ERIC Educational Resources Information Center

    Amanzio, Martina; Monteverdi, Silvia; Giordano, Alessandra; Soliveri, Paola; Filippi, Paola; Geminiani, Giuliano

    2010-01-01

    Background: This study analyzed the presence of awareness of movement disorders (dyskinesias and hypokinesias) in 25 patients with Parkinson's disease (PD) and motor fluctuations (dyskinesias, wearing off, on-off fluctuations). Of the few studies that have dealt with this topic, none have analyzed the differences in the awareness of motor deficits…

  3. ORNL research could lead to new treatment for Parkinson's

    ScienceCinema

    Boyd Evans

    2010-01-08

    Parkinson's disease can be debilitating, and right now, there is no cure. But soon, there could be one more way doctors can help fight off the symptoms of that disease, along with stroke and brain tumors. It's all because of research conducted over the past five years at the Oak Ridge National Laboratory.

  4. Anatomic and physiological considerations in pallidotomy for Parkinson's disease.

    PubMed

    Dogali, M; Berić, A; Sterio, D; Eidelberg, D; Fazzini, E; Takikawa, S; Samelson, D R; Devinsky, O; Kolodny, E H

    1995-01-01

    Our ongoing study of ventral pallidotomy for the control of Parkinson's disease in selected patients has provided the opportunity to explore the topographical and somatotopic organization of the human globus pallidus. Utilizing microelectrode techniques we have obtained recordings which were correlated with data from MPTP-parkinsonian primates. In addition, we performed pre- and post-operative FDG/PET scans in these patients. Our studies reveal similarities between the MPTP-parkinsonian primate model and human Parkinson's disease in terms of physiologic recordings and responses. However, we have encountered significant differences between dominant and non-dominant hemisphere representations, particularly for the hand, in the human. In addition, our PET studies confirmed, as in previous parkinsonian primate models, glucose hypermetabolism in the lenticular area of Parkinson's disease patients. This hypermetabolism is dramatically altered by creation of a lesion in the globus pallidus medialis. This is demonstrated by follow-up PET scans which reveal not only a decrease in metabolism of the operated lenticular region, but also in the frontal cortical projections. These combined observations of the cellular activity in the globus pallidus and the observed changes in PET metabolism support the selection of the pallidum for lesioning and control of Parkinson's disease, and offer insight into the underlying physiology of this disorder. The above physiological and PET data will be clinically correlated with our ongoing series of 35+ patients. PMID:8748575

  5. Impaired Emotion Recognition in Music in Parkinson's Disease

    ERIC Educational Resources Information Center

    van Tricht, Mirjam J.; Smeding, Harriet M. M.; Speelman, Johannes D.; Schmand, Ben A.

    2010-01-01

    Music has the potential to evoke strong emotions and plays a significant role in the lives of many people. Music might therefore be an ideal medium to assess emotion recognition. We investigated emotion recognition in music in 20 patients with idiopathic Parkinson's disease (PD) and 20 matched healthy volunteers. The role of cognitive dysfunction…

  6. Wolff-Parkinson-white syndrome mimics a conduction disease.

    PubMed

    Marrakchi, S; Kammoun, I; Kachboura, S

    2014-01-01

    Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a "false positive" of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope. PMID:25114686

  7. Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

    PubMed Central

    Marrakchi, S.; Kammoun, I.; Kachboura, S.

    2014-01-01

    Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a “false positive” of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope. PMID:25114686

  8. Roles of PTEN with DNA Repair in Parkinson's Disease.

    PubMed

    Ogino, Mako; Ichimura, Mayuko; Nakano, Noriko; Minami, Akari; Kitagishi, Yasuko; Matsuda, Satoru

    2016-01-01

    Oxidative stress is considered to play key roles in aging and pathogenesis of many neurodegenerative diseases such as Parkinson's disease, which could bring DNA damage by cells. The DNA damage may lead to the cell apoptosis, which could contribute to the degeneration of neuronal tissues. Recent evidence suggests that PTEN (phosphatase and tensin homolog on chromosome 10) may be involved in the pathophysiology of the neurodegenerative disorders. Since PTEN expression appears to be one dominant determinant of the neuronal cell death, PTEN should be a potential molecular target of novel therapeutic strategies against Parkinson's disease. In addition, defects in DNA damage response and DNA repair are often associated with modulation of hormone signaling pathways. Especially, many observations imply a role for estrogen in a regulation of the DNA repair action. In the present review, we have attempted to summarize the function of DNA repair molecules at a viewpoint of the PTEN signaling pathway and the hormone related functional modulation of cells, providing a broad interpretation on the molecular mechanisms for treatment of Parkinson's disease. Particular attention will be paid to the mechanisms proposed to explain the health effects of food ingredients against Parkinson's disease related to reduce oxidative stress for an efficient therapeutic intervention. PMID:27314344

  9. Analysis of Mitochondrial haemoglobin in Parkinson's disease brain.

    PubMed

    Shephard, Freya; Greville-Heygate, Oliver; Liddell, Susan; Emes, Richard; Chakrabarti, Lisa

    2016-07-01

    Mitochondrial dysfunction is an early feature of neurodegeneration. We have shown there are mitochondrial haemoglobin changes with age and neurodegeneration. We hypothesised that altered physiological processes are associated with recruitment and localisation of haemoglobin to these organelles. To confirm a dynamic localisation of haemoglobin we exposed Drosophila melanogaster to cyclical hypoxia with recovery. With a single cycle of hypoxia and recovery we found a relative accumulation of haemoglobin in the mitochondria compared with the cytosol. An additional cycle of hypoxia and recovery led to a significant increase of mitochondrial haemoglobin (p<0.05). We quantified ratios of human mitochondrial haemoglobin in 30 Parkinson's and matched control human post-mortem brains. Relative mitochondrial/cytosolic quantities of haemoglobin were obtained for the cortical region, substantia nigra and cerebellum. In age matched post-mortem brain mitochondrial haemoglobin ratios change, decreasing with disease duration in female cerebellum samples (n=7). The change is less discernible in male cerebellum (n=18). In cerebellar mitochondria, haemoglobin localisation in males with long disease duration shifts from the intermembrane space to the outer membrane of the organelle. These new data illustrate dynamic localisation of mitochondrial haemoglobin within the cell. Mitochondrial haemoglobin should be considered in the context of gender differences characterised in Parkinson's disease. It has been postulated that cerebellar circuitry may be activated to play a protective role in individuals with Parkinson's. The changing localisation of intracellular haemoglobin in response to hypoxia presents a novel pathway to delineate the role of the cerebellum in Parkinson's disease. PMID:27181046

  10. Neural Substrates of Cognitive Skill Learning in Parkinson's Disease

    ERIC Educational Resources Information Center

    Beauchamp, M. H.; Dagher, A.; Panisset, M.; Doyon, J.

    2008-01-01

    While cognitive skill learning is normally acquired implicitly through frontostrial circuitry in healthy individuals, neuroimaging studies suggest that patients with Parkinson's disease (PD) do so by activating alternate, intact brain areas associated with explicit memory processing. To further test this hypothesis, 10 patients with PD and 12…

  11. Feasibility of Group Voice Therapy for Individuals with Parkinson's Disease

    ERIC Educational Resources Information Center

    Searl, Jeff; Wilson, Kristel; Haring, Karen; Dietsch, Angela; Lyons, Kelly; Pahwa, Rajesh

    2011-01-01

    Purpose: The primary purpose was to demonstrate the feasibility of executing treatment tasks focused on increasing loudness in a group format for individuals with Parkinson's disease (PD). A second purpose was to report preliminary pre-to-post treatment outcomes for individuals with PD immediately after they complete the group program. Methods:…

  12. Caring for the Student with Wolff-Parkinson-White Syndrome

    ERIC Educational Resources Information Center

    Prenni, Patricia G.

    2009-01-01

    Wolff-Parkinson-White syndrome is a cardiac condition in which an extra electrical pathway within the heart causes an abnormal increase in heart rate. It affects one to three people of every 1,000 people worldwide, occurring more often in males. Diagnosis usually occurs during young adulthood, so it is important for school nurses to be familiar…

  13. Emotional Changes with Multiple Sclerosis and Parkinson's Disease.

    ERIC Educational Resources Information Center

    Rao, Stephen M.; And Others

    1992-01-01

    Examines specific methodological issues associated with research in area of emotional disorders among patients with multiple sclerosis (MS) or Parkinson's disease (PD); describes range and severity of emotional disorders in MS and PD; and examines both endogenous and reactive explanations to account for increased prevalence of emotional…

  14. Swallowing Disorders in Parkinson's Disease: Impact of Lingual Pumping

    ERIC Educational Resources Information Center

    Argolo, Natalie; Sampaio, Marília; Pinho, Patrícia; Melo, Ailton; Nóbrega, Ana Caline

    2015-01-01

    Background: Lingual pumping (LP) is a repetitive, involuntary, anteroposterior movement of the tongue on the soft palate that is executed prior to transferring the food bolus to the pharynx, but we also observed LP when multiple swallows were taken. LP may be associated with rigidity and bradykinesia in patients with Parkinson's disease (PD). This…

  15. Autosomal dominant Parkinson's disease caused by SNCA duplications.

    PubMed

    Konno, Takuya; Ross, Owen A; Puschmann, Andreas; Dickson, Dennis W; Wszolek, Zbigniew K

    2016-01-01

    The discovery in 1997 that mutations in the SNCA gene cause Parkinson's disease (PD) greatly advanced our understanding of this illness. There are pathogenic missense mutations and multiplication mutations in SNCA. Thus, not only a mutant protein, but also an increased dose of wild-type protein can produce autosomal dominant parkinsonism. We review the literature on SNCA duplications and focus on pathologically-confirmed cases. We also report a newly-identified American family with SNCA duplication whose proband was autopsied. We found that over half of the reported cases with SNCA duplication had early-onset parkinsonism and non-motor features, such as dysautonomia, rapid eye movement sleep behavior disorder (RBD), hallucinations (usually visual) and cognitive deficits leading to dementia. Only a few cases have presented with typical features of PD. Our case presented with depression and RBD that preceded parkinsonism, and dysautonomia that led to an initial diagnosis of multiple system atrophy. Dementia and visual hallucinations followed. Our patient and the other reported cases with SNCA duplications had widespread cortical Lewy pathology. Neuronal loss in the hippocampal cornu ammonis 2/3 regions were seen in about half of the autopsied SNCA duplication cases. Similar pathology was also observed in SNCA missense mutation and triplication carriers. PMID:26350119

  16. Freezing of Gait in Parkinsonism and its Potential Drug Treatment.

    PubMed

    Zhang, Li-Li; Canning, S Duff; Wang, Xiao-Ping

    2016-01-01

    Freezing of gait (FOG) is a heterogeneous symptom. Studies of treatment for FOG are scarce. Levodopa and monoamine oxidase inhibitors (rasagiline and selegiline) have shown effective improvement for FOG. Other drugs, such as L-threo-3, 4-dihydroxyphenylserine, amantadine, and botulinum toxin have exhibited some beneficial effects. The present review summarizes the potential drug treatment for FOG in Parkinsonism. PMID:26635194

  17. Linguistic Correlates of Asymmetric Motor Symptom Severity in Parkinson's Disease

    ERIC Educational Resources Information Center

    Holtgraves, Thomas; McNamara, Patrick; Cappaert, Kevin; Durso, Raymond

    2010-01-01

    Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N = 31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the…

  18. When Are High-Tech Communicators Effective in Parkinson's Disease?

    ERIC Educational Resources Information Center

    Ferriero, Giorgio; Caligari, Marco; Ronconi, Gianpaolo; Franchignoni, Franco

    2012-01-01

    This report describes a 63-year-old woman with Parkinson's disease showing loss of intelligibility of speech and severely impaired handwriting, despite undergoing physical and speech therapies. As the patient had sufficient residual motor abilities and adequate cognitive function and motivation, a computer-based communication aid with a software…

  19. Horizontal and Vertical Attentional Orienting in Parkinson's Disease

    ERIC Educational Resources Information Center

    Nys, Gudrun M. S.; Santens, Patrick; Vingerhoets, Guy

    2010-01-01

    Patients with Parkinson's disease (PD) typically suffer from an asymmetric degeneration of dopaminergic cells in the substantia nigra, resulting in right-sided (RPD) or left-sided (LPD) predominance of motor symptomatology. As the dopaminergic system is also involved in attention, we examined horizontal and vertical orienting of attention in LPD…

  20. Lingual Kinematics during Rapid Syllable Repetition in Parkinson's Disease

    ERIC Educational Resources Information Center

    Wong, Min Ney; Murdoch, Bruce E.; Whelan, Brooke-Mai

    2012-01-01

    Background: Rapid syllable repetition tasks are commonly used in the assessment of motor speech disorders. However, little is known about the articulatory kinematics during rapid syllable repetition in individuals with Parkinson's disease (PD). Aims: To investigate and compare lingual kinematics during rapid syllable repetition in dysarthric…

  1. Nonmotor Symptoms in a Malaysian Parkinson's Disease Population

    PubMed Central

    Azmin, Shahrul; Khairul Anuar, Abdul Manaf; Tan, Hui Jan; Nafisah, Wan Yahya; Raymond, Azman Ali; Hanita, Othman; Shah, Shamsul Azhar; Norlinah, Mohamed Ibrahim

    2014-01-01

    Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson's disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson's disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson's disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0–8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (rs: 0.727, P < 0.001). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson's disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study. PMID:24800102

  2. Parkinson's Law quantified: three investigations on bureaucratic inefficiency

    NASA Astrophysics Data System (ADS)

    Klimek, Peter; Hanel, Rudolf; Thurner, Stefan

    2009-03-01

    We formulate three famous, descriptive essays of Parkinson on bureaucratic inefficiency in a quantifiable and dynamical socio-physical framework. In the first model we show how the use of recent opinion formation models for small groups can be used to understand Parkinson's observation that decision-making bodies such as cabinets or boards become highly inefficient once their size exceeds a critical 'Coefficient of Inefficiency', typically around 20. A second observation of Parkinson—which is sometimes referred to as Parkinson's Law—is that the growth of bureaucratic or administrative bodies usually goes hand in hand with a drastic decrease of its overall efficiency. In our second model we view a bureaucratic body as a system of a flow of workers, who enter, become promoted to various internal levels within the system over time, and leave the system after having served for a certain time. Promotion usually is associated with an increase of subordinates. Within the proposed model it becomes possible to work out the phase diagram under which conditions of bureaucratic growth can be confined. In our last model we assign individual efficiency curves to workers throughout their life in administration, and compute the optimum time to give them the old age pension, in order to ensure a maximum of efficiency within the body—in Parkinson's words we compute the 'Pension Point'.

  3. Medication Impairs Probabilistic Classification Learning in Parkinson's Disease

    ERIC Educational Resources Information Center

    Jahanshahi, Marjan; Wilkinson, Leonora; Gahir, Harpreet; Dharminda, Angeline; Lagnado, David A.

    2010-01-01

    In Parkinson's disease (PD), it is possible that tonic increase of dopamine associated with levodopa medication overshadows phasic release of dopamine, which is essential for learning. Thus while the motor symptoms of PD are improved with levodopa medication, learning would be disrupted. To test this hypothesis, we investigated the effect of…

  4. Dynamic Structure of Emotions Among Individuals with Parkinson's Disease

    ERIC Educational Resources Information Center

    Chow, Sy-Miin; Nesselroade, John R.; Shifren, Kim; McArdle, John J.

    2004-01-01

    With few exceptions, the dynamics underlying the mood structures of individuals with Parkinson's Disease have consistently been overlooked. Based on 12 participants' daily self-reports over 72 days, we identified 10 participants whose covariance matrices for positive and negative affect were similar enough to warrant pooling. Dynamic factor models…

  5. ORNL research could lead to new treatment for Parkinson's

    SciTech Connect

    Boyd Evans

    2009-08-12

    Parkinson's disease can be debilitating, and right now, there is no cure. But soon, there could be one more way doctors can help fight off the symptoms of that disease, along with stroke and brain tumors. It's all because of research conducted over the past five years at the Oak Ridge National Laboratory.

  6. Evaluation of Nonmotor Symptoms in Diagnosis of Parkinsonism and Tremor

    PubMed Central

    Chai, Chiun-Hian

    2016-01-01

    Background. Nonmotor symptoms particularly olfactory dysfunction, RBD, depression, hallucinations, and constipation are currently not included in the typical clinical criteria for diagnosing Lewy body Parkinsonian disorders (LBPD). The aim of this study is to determine the diagnostic value of nonmotor symptoms in patients presenting with Parkinsonism and tremor. Methods. All new patients seen between January 2007 and May 2013 in the Movement Disorders Specialist Clinics of the Royal Melbourne Hospital (RMH), who were referred with a possible neurodegenerative syndrome or concerns of Parkinsonism and/or tremor, were included. Patients underwent routine evaluation with the four-minute “Sniffin Sticks” test, RBD, depression, and constipation. Results. 291 patients were included in the analysis. Conclusion. We found that lower olfaction scores based on “Sniffin Sticks” testing combined with reports of depression and constipation are independent predictors for the diagnosis of the spectrum of Lewy body Parkinsonian disorders (LBPD). Parkinson's disease (PD) cannot be reliably clinically differentiated from other causes of Parkinsonism that share symptomatology and structural abnormalities. PMID:27403372

  7. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease

    PubMed Central

    Neumann, Juliane; Bras, Jose; Deas, Emma; O'Sullivan, Sean S.; Parkkinen, Laura; Lachmann, Robin H.; Li, Abi; Holton, Janice; Guerreiro, Rita; Paudel, Reema; Segarane, Badmavady; Singleton, Andrew; Lees, Andrew; Hardy, John; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W.

    2009-01-01

    Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, the most common lysosomal storage disorder. Parkinsonism is an established feature of Gaucher's disease and an increased frequency of mutations in GBA has been reported in several different ethnic series with sporadic Parkinson's disease. In this study, we evaluated the frequency of GBA mutations in British patients affected by Parkinson's disease. We utilized the DNA of 790 patients and 257 controls, matched for age and ethnicity, to screen for mutations within the GBA gene. Clinical data on all identified GBA mutation carriers was reviewed and analysed. Additionally, in all cases where brain material was available, a neuropathological evaluation was performed and compared to sporadic Parkinson's disease without GBA mutations. The frequency of GBA mutations among the British patients (33/790 = 4.18%) was significantly higher (P = 0.01; odds ratio = 3.7; 95% confidence interval = 1.12–12.14) when compared to the control group (3/257 = 1.17%). Fourteen different GBA mutations were identified, including three previously undescribed mutations, K7E, D443N and G193E. Pathological examination revealed widespread and abundant α-synuclein pathology in all 17 GBA mutation carriers, which were graded as Braak stage of 5–6, and had McKeith's limbic or diffuse neocortical Lewy body-type pathology. Diffuse neocortical Lewy body-type pathology tended to occur more frequently in the group with GBA mutations compared to matched Parkinson's disease controls. Clinical features comprised an early onset of the disease, the presence of hallucinations in 45% (14/31) and symptoms of cognitive decline or dementia in 48% (15/31) of patients. This study demonstrates that GBA mutations are found in British subjects at a higher frequency than any other known Parkinson's disease gene. This is the largest study to date on a non-Jewish patient sample with a detailed genotype/phenotype/pathological analyses

  8. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.

    PubMed

    Neumann, Juliane; Bras, Jose; Deas, Emma; O'Sullivan, Sean S; Parkkinen, Laura; Lachmann, Robin H; Li, Abi; Holton, Janice; Guerreiro, Rita; Paudel, Reema; Segarane, Badmavady; Singleton, Andrew; Lees, Andrew; Hardy, John; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W

    2009-07-01

    Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, the most common lysosomal storage disorder. Parkinsonism is an established feature of Gaucher's disease and an increased frequency of mutations in GBA has been reported in several different ethnic series with sporadic Parkinson's disease. In this study, we evaluated the frequency of GBA mutations in British patients affected by Parkinson's disease. We utilized the DNA of 790 patients and 257 controls, matched for age and ethnicity, to screen for mutations within the GBA gene. Clinical data on all identified GBA mutation carriers was reviewed and analysed. Additionally, in all cases where brain material was available, a neuropathological evaluation was performed and compared to sporadic Parkinson's disease without GBA mutations. The frequency of GBA mutations among the British patients (33/790 = 4.18%) was significantly higher (P = 0.01; odds ratio = 3.7; 95% confidence interval = 1.12-12.14) when compared to the control group (3/257 = 1.17%). Fourteen different GBA mutations were identified, including three previously undescribed mutations, K7E, D443N and G193E. Pathological examination revealed widespread and abundant alpha-synuclein pathology in all 17 GBA mutation carriers, which were graded as Braak stage of 5-6, and had McKeith's limbic or diffuse neocortical Lewy body-type pathology. Diffuse neocortical Lewy body-type pathology tended to occur more frequently in the group with GBA mutations compared to matched Parkinson's disease controls. Clinical features comprised an early onset of the disease, the presence of hallucinations in 45% (14/31) and symptoms of cognitive decline or dementia in 48% (15/31) of patients. This study demonstrates that GBA mutations are found in British subjects at a higher frequency than any other known Parkinson's disease gene. This is the largest study to date on a non-Jewish patient sample with a detailed genotype/phenotype/pathological analyses

  9. Biomarkers of Parkinson's disease: present and future.

    PubMed

    Miller, Diane B; O'Callaghan, James P

    2015-03-01

    Sporadic or idiopathic Parkinson's disease (PD) is an age-related neurodegenerative disorder of unknown origin that ranks only second behind Alzheimer's disease (AD) in prevalence and its consequent social and economic burden. PD neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta; however, more widespread involvement of other CNS structures and peripheral tissues now is widely documented. The onset of molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD. The hallmark symptoms of PD, resting tremors, rigidity and postural disabilities, are related to dopamine (DA) deficiency. Current therapies treat these symptoms by replacing or boosting existing DA. All current interventions have limited therapeutic benefit for disease progression because damage likely has progressed over an estimated period of ~5 to 15years to a loss of 60%-80% of the nigral DA neurons, before symptoms emerge. There is no accepted definitive biomarker of PD. An urgent need exists to develop early diagnostic biomarkers for two reasons: (1) to intervene at the onset of disease and (2) to monitor the progress of therapeutic interventions that may slow or stop the course of the disease. In the context of disease development, one of the promises of personalized medicine is the ability to predict, on an individual basis, factors contributing to the susceptibility for the development of a given disease. Recent advances in our understanding of genetic factors underlying or contributing to PD offer the potential for monitoring susceptibility biomarkers that can be used to identify at-risk individuals and possibly prevent the onset of disease through treatment. Finally, the exposome concept is new in the biomarker discovery arena and it is suggested as a way to move forward in identifying biomarkers of neurological diseases. It is a two-stage scheme involving a first stage

  10. Association Between Tuberculosis and Parkinson Disease

    PubMed Central

    Shen, Chih-Hao; Chou, Chung-Hsing; Liu, Feng-Cheng; Lin, Te-Yu; Huang, Wen-Yen; Wang, Yu-Chiao; Kao, Chia-Hung

    2016-01-01

    Abstract Few studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB. We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models. A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30–1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02–2.52), hypertension (aHR: 2.23, 95% CI: 2.04–2.44), head injury (aHR: 2.32, 95% CI: 1.95–2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49–2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66–2.05), depression (aHR: 4.66, 95% CI: 3.59–6.05), dementia (aHR: 3.70, 95% CI: 2.99–4.59), and stroke (aHR: 2.56, 95% CI: 2.28–2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58–2.00) and decreased with the follow-up period in the TB cohort. Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients. PMID:26937925

  11. Biomarkers in Parkinson's disease (recent update).

    PubMed

    Sharma, Sushil; Moon, Carolyn Seungyoun; Khogali, Azza; Haidous, Ali; Chabenne, Anthony; Ojo, Comfort; Jelebinkov, Miriana; Kurdi, Yousef; Ebadi, Manuchair

    2013-09-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder mostly affecting the aging population over sixty. Cardinal symptoms including, tremors, muscle rigidity, drooping posture, drooling, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons are already destroyed. Hence we need early, sensitive, specific, and economical peripheral and/or central biomarker(s) for the differential diagnosis, prognosis, and treatment of PD. These can be classified as clinical, biochemical, genetic, proteomic, and neuroimaging biomarkers. Novel discoveries of genetic as well as nongenetic biomarkers may be utilized for the personalized treatment of PD during preclinical (premotor) and clinical (motor) stages. Premotor biomarkers including hyper-echogenicity of substantia nigra, olfactory and autonomic dysfunction, depression, hyposmia, deafness, REM sleep disorder, and impulsive behavior may be noticed during preclinical stage. Neuroimaging biomarkers (PET, SPECT, MRI), and neuropsychological deficits can facilitate differential diagnosis. Single-cell profiling of dopaminergic neurons has identified pyridoxal kinase and lysosomal ATPase as biomarker genes for PD prognosis. Promising biomarkers include: fluid biomarkers, neuromelanin antibodies, pathological forms of α-Syn, DJ-1, amyloid β and tau in the CSF, patterns of gene expression, metabolomics, urate, as well as protein profiling in the blood and CSF samples. Reduced brain regional N-acetyl-aspartate is a biomarker for the in vivo assessment of neuronal loss using magnetic resonance spectroscopy and T2 relaxation time with MRI. To confirm PD diagnosis, the PET biomarkers include [(18)F]-DOPA for estimating dopaminergic neurotransmission, [(18)F]dG for mitochondrial bioenergetics, [(18)F]BMS for mitochondrial complex-1, [(11)C](R)-PK11195 for microglial activation, SPECT imaging with (123)Iflupane and βCIT for dopamine transporter, and urinary

  12. Investigation of Urination Disorder in Parkinson's Disease

    PubMed Central

    Zhang, Li-Mei; Zhang, Xu-Ping

    2015-01-01

    Background: Urination disorders are common in Parkinson's disease (PD) and respond poorly to medication. This study aimed to analyze the risk factors for urination disorders in PD. Methods: Ninety-one patients with PD (aged 34–83 years old) were recruited. Patients were assessed with the Unified PD Rating Scale (UPDRS), Hoehn and Yahr stage, Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Scale (HAMA). Micturition number was recorded, and Type B ultrasound was used to evaluate residual urine. Statistics was performed using binary logistic regression, bivariate correlations, and Chi-square and t-tests. Results: Of 91 patients, urinary dysfunction occurred in 55.0%. Among these, 49.5% suffered with nocturia, 47.3% with pollakiuria. Nocturia number had a positive linear relationship with HAMA score (odds ratio [OR] = 0.340, P = 0.001), HAMD score (OR = 0.323, P = 0.002), duration of L-dopa medication (OR = 0.328, P = 0.001), dose of L-dopa (OR = 0.273, P = 0.009), UPDRS-II (OR = 0.402, P = 0.000), UPDRS-III score (OR = 0.291, P = 0.005), and PSQI score (OR = 0.249, P = 0.017). Micturition number over 24 h was positively associated with HAMA (OR = 0.303, P = 0.004) and UPDRS-II scores (OR = 0.306, P = 0.003). Of patients with residual urine, 79.3% had a volume of residual urine <50 ml. Residual urine was present in 44.4% of the patients with nocturia, 46.5% of the patients with pollakiuria, and 80.0% of the patients with dysuria. More men than women had residual urine (35.2% male vs. 13.3% female; P = 0.002). Conclusions: Nocturia and pollakiuria were common micturition symptoms in our participants with PD. Nocturia was associated with depression, anxiety, sleep problems, and severity of PD. Pollakiuria was associated with anxiety and severity of PD. Male patients were more prone to residual urine and pollakiuria. PMID:26521789

  13. Ventricular dilatation and brain atrophy in patients with Parkinson's disease with incipient dementia.

    PubMed

    Camicioli, Richard; Sabino, Jennifer; Gee, Myrlene; Bouchard, Thomas; Fisher, Nancy; Hanstock, Chris; Emery, Derek; Martin, W R Wayne

    2011-07-01

    Age-related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age- and sex-matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1-weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini-Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss. PMID:21442661

  14. Trib3 Is Elevated in Parkinson's Disease and Mediates Death in Parkinson's Disease Models

    PubMed Central

    Sun, Xiaotian; Zareen, Neela; Rao, Apeksha; Berman, Zachary; Volpicelli-Daley, Laura; Bernd, Paulette; Crary, John F.; Levy, Oren A.; Greene, Lloyd A.

    2015-01-01

    Parkinson's disease (PD) is characterized by the progressive loss of select neuronal populations, but the prodeath genes mediating the neurodegenerative processes remain to be fully elucidated. Trib3 (tribbles pseudokinase 3) is a stress-induced gene with proapoptotic activity that was previously described as highly activated at the transcriptional level in a 6-hydroxydopamine (6-OHDA) cellular model of PD. Here, we report that Trib3 immunostaining is elevated in dopaminergic neurons of the substantia nigra pars compacta (SNpc) of human PD patients. Trib3 protein is also upregulated in cellular models of PD, including neuronal PC12 cells and rat dopaminergic ventral midbrain neurons treated with 6-OHDA, 1-methyl-4-phenylpyridinium (MPP+), or α-synuclein fibrils (αSYN). In the toxin models, Trib3 induction is substantially mediated by the transcription factors CHOP and ATF4. Trib3 overexpression is sufficient to promote neuronal death; conversely, Trib3 knockdown protects neuronal PC12 cells as well as ventral midbrain dopaminergic neurons from 6-OHDA, MPP+, or αSYN. Mechanism studies revealed that Trib3 physically interacts with Parkin, a prosurvival protein whose loss of function is associated with PD. Elevated Trib3 reduces Parkin expression in cultured cells; and in the SNpc of PD patients, Parkin levels are reduced in a subset of dopaminergic neurons expressing high levels of Trib3. Loss of Parkin at least partially mediates the prodeath actions of Trib3 in that Parkin knockdown in cellular PD models abolishes the protective effect of Trib3 downregulation. Together, these findings identify Trib3 and its regulatory pathways as potential targets to suppress the progression of neuron death and degeneration in PD. SIGNIFICANCE STATEMENT Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Current treatments ameliorate symptoms, but not the underlying neuronal death. Understanding the core neurodegenerative processes in PD is a

  15. Drug-induced Parkinsonism versus Idiopathic Parkinson Disease: Utility of Nigrosome 1 with 3-T Imaging.

    PubMed

    Sung, Young Hee; Noh, Young; Lee, Jongho; Kim, Eung Yeop

    2016-06-01

    Purpose To explore the utility of nigrosome 1 with 3-T magnetic resonance (MR) imaging to differentiate idiopathic Parkinson disease (IPD) from drug-induced parkinsonism (DIP). Materials and Methods The institutional review board approved this study, and participants gave informed consent. This study enrolled patients with DIP (n = 20) and IPD (n = 29) who underwent N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl)nortropane ((18)F-FP-CIT) positron emission tomography (PET) and healthy participants (n = 20). All participants underwent 0.5 × 0.5 × 1.0 mm(3) oblique axial three-dimensional multiecho-data image combination imaging to view the nigrosome 1 with 3-T imaging. Two reviewers independently assessed the nigrosome 1 without clinical information. DIP was diagnosed when no abnormality was seen at (18)F-FP-CIT PET. Diagnostic sensitivity, specificity, and accuracy of the nigrosome 1 imaging were evaluated between the IPD and DIP patients and between the IPD patients and healthy participants. Interrater agreement was assessed with Cohen κ. Results Both reviewers agreed in 63 of 69 participants (91.3%) for the presence of any abnormality on either side of the nigrosome 1 (κ = 0.825). Findings in all 29 IPD patients (100%) and three of 20 DIP patients (15%) were rated as abnormal and in 17 of 20 DIP patients (85%) they were interpreted as normal on the basis of imaging of the nitgrosome 1 (sensitivity, 100% (29 of 29); specificity, 85.0% (17 of 20); accuracy, 93.9% (46 of 49) between IPD and DIP patients). Findings in 3 of 20 healthy participants (15.0%) were interpreted as abnormal on the basis of imaging the nigrosome 1 while in the other 17 of 20 healthy participants (85.0%) they were rated as normal (sensitivity, 100% [29 of 29]; specificity, 85.0% [17 of 20]; accuracy, 93.9% [46 of 49] between IPD patients and healthy participants [κ = 0.831]). Conclusion The imaging of nigrosome 1 with 3-T imaging can differentiate DIP from IPD with high accuracy and

  16. Parkinsonism and Neurological Manifestations of Influenza Throughout the 20th and 21st Centuries

    PubMed Central

    Henry, Julie; Smeyne, Richard J.; Jang, Haeman; Miller, Bayard; Okun, Michael S.

    2015-01-01

    Purpose Given the recent paper by Jang et al. on “A Highly Pathogenic H5N1 Influenza Virus” which reported a novel animal model of parkinsonism, we aimed to perform a complete historical review of the 20th and 21st century literature on parkinsonism and neurological manifestations of influenza. Scope There were at least twelve major flu pandemics reported in the literature in the 20th and 21st century. Neurological manifestations most prevalent during the pandemics included delirium, encephalitis, ocular abnormalities, amyotrophy, myelopathy, radiculopathy, ataxia and seizures. Very little parkinsonism was reported with the exception of the 1917 cases originally described by von Economo. Conclusions To date there have been surprisingly few cases of neurological issues inclusive of parkinsonism associated with influenza pandemics. Given the recent animal model of H5N1 influenza associated parkinsonism, the medical establishment should be prepared to evaluate for the re-emergence of parkinsonism during future outbreaks. PMID:20650672

  17. The safety, tolerability and efficacy of pimavanserin tartrate in the treatment of psychosis in Parkinson's disease.

    PubMed

    Hermanowicz, Stefan; Hermanowicz, Neal

    2016-06-01

    Parkinson's disease psychosis (PDP) is a common and often very disturbing component of Parkinson's disease (PD). PDP consists of hallucinations that are mainly visual and delusions that are often of a paranoid nature. These symptoms can be the most troubling and disruptive of all the manifestations of Parkinson's disease. Current treatment methods include the reduction of anti-Parkinson's medications, a strategy that may worsen the motor problems the medications are prescribed to alleviate, and the introduction of selected antipsychotic medications that carry with them the potential for troubling side effects and serious consequences. Pimavanserin has been developed and studied in clinical trials to specifically address Parkinson's disease psychosis and has been submitted to the U.S. Food and Drug Administration for its approval for this purpose. If this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis. PMID:26908168

  18. Atomoxetine restores the response inhibition network in Parkinson's disease.

    PubMed

    Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-08-01

    Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction

  19. Pathways to Parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson's disease.

    PubMed

    Kumaran, Ravindran; Cookson, Mark R

    2015-10-15

    In the past few years, there have been a large number of genes identified that contribute to the lifetime risk of Parkinson's disease (PD). Some genes follow a Mendelian inheritance pattern, but others are risk factors for apparently sporadic PD. Here, we will focus on those genes nominated by genome-wide association studies (GWAS) in sporadic PD, with a particular emphasis on genes that overlap between familial and sporadic disease such as those encoding a-synuclein (SNCA), tau (MAPT), and leucine-rich repeat kinase 2 (LRRK2). We will advance the view that there are likely relationships between these genes that map not only to neuronal processes, but also to neuroinflammation. We will particularly discuss evidence for a role of PD proteins in microglial activation and regulation of the autophagy-lysosome system that is dependent on microtubule transport in neurons. Thus, there are at least two non-mutually exclusive pathways that include both non-cell-autonomous and cell-autonomous mechanisms in the PD brain. Collectively, these data have highlighted the amount of progress made in understanding PD and suggest ways forward to further dissect this disorder. PMID:26101198

  20. Mitochondrial DNA in CSF distinguishes LRRK2 from idiopathic Parkinson's disease.

    PubMed

    Podlesniy, Petar; Vilas, Dolores; Taylor, Peggy; Shaw, Leslie M; Tolosa, Eduard; Trullas, Ramon

    2016-10-01

    Mitochondrial DNA regulates mitochondrial function which is altered in both idiopathic and familial forms of Parkinson's disease. To investigate whether these two disease forms exhibit an altered regulation of mitochondrial DNA we measured cell free mitochondrial DNA content in cerebrospinal fluid (CSF) from idiopathic and LRRK2-related Parkinson's disease patients. The concentration of mitochondrial DNA was measured using a digital droplet polymerase chain reaction technique in a total of 98 CSF samples from a cohort of subjects including: 20 LRRK2(G2019S) mutation carriers with Parkinson's disease, 26 asymptomatic LRRK2(G2019S) mutation carriers, 31 patients with idiopathic Parkinson's disease and 21 first-degree relatives of LRRK2 Parkinson's disease patients without the mutation. Here we report that LRRK2(G2019S) mutation carriers with Parkinson's disease exhibit a high concentration of mitochondrial DNA in CSF compared with asymptomatic LRRK2(G2019S) mutation carriers and with idiopathic Parkinson's disease patients. In addition, idiopathic, but not LRRK2 Parkinson's disease is associated with low CSF concentration of α-synuclein. These results show that high mitochondrial DNA content in CSF distinguishes idiopathic from LRRK2-related Parkinson's disease suggesting that different biochemical pathways underlie neurodegeneration in these two disorders. PMID:27260835

  1. The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism

    PubMed Central

    DePaolo, J.; Goker-Alpan, O.; Samaddar, T.; Lopez, G.; Sidransky, E.

    2009-01-01

    A body of work has emerged over the past decade demonstrating a relationship between mutations in glucocerebrosidase (GBA), the gene implicated in Gaucher disease, and the development of parkinsonism. Several different lines of research support this relationship. First, patients with Gaucher disease who are homozygous for mutations in GBA have a higher than expected propensity to develop Parkinson disease (PD). Furthermore, carriers of GBA mutations, particularly family members of patients with Gaucher disease have displayed an increased rate of parkinsonism. Subsequently, investigators from centers around the world screened cohorts of patients with parkinsonism for GBA mutations and found that overall, subjects with Parkinson disease as well as other Lewy body disorders have at least a five–fold increase in the number of carriers of GBA mutations as compared to age matched controls. In addition, neuropathologic studies of subjects with parkinsonism carrying GBA mutations demonstrate Lewy bodies, depletion of neurons of the substantia nigra and involvement of hippocampal layers CA2−4. While the basis for this association has yet to be elucidated, evidence continues to support the role of GBA as a Parkinson risk factor across different centers, synucleinopathies and ethnicities. Further studies of the association between Gaucher disease and parkinsonism will stimulate new insights into the pathophysisology of the two disorders, and will prove crucial for both genetic counseling of patients and family members and the design of relevant therapeutic strategies for specific patients with parkinsonism. PMID:19425057

  2. Mendelian Randomization — the Key to Understanding Aspects of Parkinson's Disease Causation?

    PubMed Central

    Nalls, Mike A.

    2015-01-01

    Parkinson's disease has multiple determinants and is associated with a wide range of exposures that appear to modify risk in traditional observational studies, including numerous lifestyle and environmental factors. Across other fields of medicine, Mendelian randomization has emerged as a powerful method to examine whether associations between exposures and disease outcomes are causal. Here we discuss the concept of Mendelian randomization, its potential relevance to Parkinson's disease, and suggest avenues through which the method could be employed to further understanding of the causal basis of Parkinson's disease. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:26695521

  3. Mendelian Randomization - the Key to Understanding Aspects of Parkinson's Disease Causation?

    PubMed

    Noyce, Alastair J; Nalls, Mike A

    2016-04-01

    Parkinson's disease has multiple determinants and is associated with a wide range of exposures that appear to modify risk in traditional observational studies, including numerous lifestyle and environmental factors. Across other fields of medicine, Mendelian randomization has emerged as a powerful method to examine whether associations between exposures and disease outcomes are causal. Here we discuss the concept of Mendelian randomization, its potential relevance to Parkinson's disease, and suggest avenues through which the method could be employed to further understanding of the causal basis of Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society. PMID:26695521

  4. Weight variation before and after surgery in Parkinson's disease: a noradrenergic modulation?

    PubMed

    Guimarães, Joana; Moura, Eduardo; Vieira-Coelho, Maria Augusta; Garrett, Carolina

    2012-08-01

    Changes in the nutritional profile of patients with Parkinson's disease have been reported before and after deep brain stimulation surgery. The major determinants of the weight variation in Parkinson's disease are not yet understood, and the mechanism seems complex. Based on the influence of the sympathetic nervous system in metabolic syndrome obesity, the intent of the present review is to consider the role of noradrenergic modulation on weight variations in Parkinson's disease. In this review the authors raise the following hypothesis: weight variation in Parkinson's disease before and after deep brain stimulation of the subthalamic nucleus could be influenced by noradrenergic interaction between the locus coeruleus, subthalamic nucleus, and hypothalamic nucleus. PMID:22700383

  5. Preclinical Parkinson's disease: detection of motor and nonmotor manifestations.

    PubMed

    Tetrud, J W

    1991-05-01

    The advent of possible protective therapies for Parkinson's disease has created a need for methods of diagnosing the disease before the clinical features become fully evident. As a number of motor and nonmotor manifestations of the disease emerge months to years before a diagnosis can be made, a battery of clinical tests might be sufficient to identify individuals at an earlier stage than is currently possible using the standard history and physical examination. A list of questions regarding possible risk factors, specific symptoms, and observations of family members could be combined in a self-administered questionnaire that might identify individuals with a high probability of early, but otherwise undiagnosable, Parkinson's disease. Identification of subtle motor features is another possible screening method. For example, handwriting and speech are commonly affected prior to diagnosis; thus, automated analysis of these motor actions might also provide detection of incipient disease. PMID:2041596

  6. [Gastroparesis and other gastrointestinal symptoms in Parkinson's disease].

    PubMed

    Santos-Garcia, D; de Deus, T; Tejera-Perez, C; Exposito-Ruiz, I; Suarez-Castro, E; Carpintero, P; Macias-Arribi, M

    2015-09-16

    Different gastrointestinal symptoms, such as excessive salivation, deterioration and other disorders affecting the teeth, dysphagia, gastroparesis, gastroesophageal reflux, constipation, difficult defecation or loss of weight are frequent events in all the stages of the development of Parkinson's disease and affect at least a third of the patients. These symptoms reflect the dysfunction of the enteric nervous system, and the stomach is one of the organs where alpha-synuclein is first deposited. Other factors, such as the dysfunction of structures in the central nervous system like the dorsal motor nucleus of the vagal nerve, hormonal factors or secondary effects deriving from the consumption of antiparkinsonian drugs, are involved in its origin. The present article offers a detailed review of the epidemiological, pathophysiological, clinical and therapeutic management aspects of the different gastrointestinal symptoms in Parkinson's disease. PMID:26350777

  7. Meanings of feeling well among women with Parkinson's disease.

    PubMed

    Olsson, Malin; Nilsson, Carina

    2015-01-01

    We conducted a qualitative inquiry to describe the meanings of feeling well as experienced by women with Parkinson's disease. Nine women were interviewed and we analysed the interviews using a reflective lifeworld approach based on phenomenological epistemology. We present the analysis as five constituents: the body as unnoticed; being able to move on; feeling joy by being connected; finding peace and harmony; and being the director of one's own life. Our findings can be used to understand and promote well-being among women with Parkinson's disease. In care meetings, knowledge about the lived and experienced health processes supports the women's striving to not let illness dominate their experience of daily life. PMID:26489404

  8. Neuroimaging biomarkers for Parkinson disease: facts and fantasy.

    PubMed

    Perlmutter, Joel S; Norris, Scott A

    2014-12-01

    In this grand rounds, we focus on development, validation, and application of neuroimaging biomarkers for Parkinson disease (PD). We cover whether such biomarkers can be used to identify presymptomatic individuals (probably yes), provide a measure of PD severity (in a limited fashion, but frequently done poorly), investigate pathophysiology of parkinsonian disorders (yes, if done carefully), play a role in differential diagnosis of parkinsonism (not well), and investigate pathology underlying cognitive impairment (yes, in conjunction with postmortem data). Along the way, we clarify several issues about definitions of biomarkers and surrogate endpoints. The goal of this lecture is to provide a basis for interpreting current literature and newly proposed clinical tools in PD. In the end, one should be able to critically distinguish fact from fantasy. PMID:25363872

  9. Iron in Parkinson disease, blood diseases, malaria and ferritin

    NASA Astrophysics Data System (ADS)

    Bauminger, E. R.; Nowik, I.

    1998-12-01

    The concentration of iron in Substantia nigra, the part of the brain which is involved in Parkinson disease, has been found by Mössbauer spectroscopy (MS) to be ~ 160 μg/g wet tissue and ~ 670 μg/g dry weight, both in control and Parkinson samples. All the iron observed by MS in these samples is ferritin-like iron. In several blood diseases, large amounts of ferritin-like iron have been observed in red blood cells. Desferral removed iron from serum, but not from red blood cells. The iron compound in the malarial pigment of human blood infected by P. falciparum was found to be hemin-like, whereas the pigment iron in rats infected by P. berghei was different from any known iron porphyrin.

  10. Adrenal Pheochromocytoma Incidentally Discovered in a Patient With Parkinsonism

    PubMed Central

    Petramala, Luigi; Concistrè, Antonio; Marinelli, Cristiano; Zinnamosca, Laura; Iannucci, Gino; Lucia, Piernatale; De Vincentis, Giuseppe; Letizia, Claudio

    2015-01-01

    Abstract To evaluate the diagnostic route of pheochromocytoma (PHEO) in a patient under dopaminergic treatment. A 70-year-old man with Parkinsonism and under treatment with levodopa and carbidopa came to our observation for evaluation of arterial hypertension and right adrenal mass discovered incidentally. To evaluate adrenal hormone levels we performed a dexamethasone suppression test, plasma aldosterone levels and 24-hr urinary metanephrine, which revealed elevated levels of catecholamines metabolities. 123-I-metaiodobenzylguanidine SPECT scintiscan revealed raised activity within the right adrenal gland concordant with the mass. The diagnosis of PHEO was posed and an elective laparoscopic adrenalectomy was performed; histopathological examination confirmed the PHEO diagnosis. Recently the coexistence of PHEO and Parkinsonism is a very rare association of diseases, with only 3 cases reported in literature. In this article, another case is reported and diagnostic procedures are discussed. PMID:26496334

  11. Current concepts in the diagnosis and management of Parkinson's disease

    PubMed Central

    Guttman, Mark; Kish, Stephen J.; Furukawa, Yoshiaki

    2003-01-01

    PARKINSON'S DISEASE IS A PROGRESSIVE NEUROLOGICAL disorder characterized by rest tremor, bradykinesia, rigidity and postural instability. The cause is unknown, but growing evidence suggests that it may be due to a combination of environmental and genetic factors. Treatment during the early stage of Parkinson's disease has evolved, and evidence suggests that dopamine agonist monotherapy may prevent the response fluctuations that are associated with disease progression. L-dopa therapy, however, remains the most efficacious treatment. Treatment during the advanced stage focuses on improving control of a number of specific clinical problems. Successful management of motor response fluctuations (e.g., “wearing off,” on–off fluctuations, nighttime deterioration, early morning deterioration and dyskinesias) and of psychiatric problems is often possible with specific treatment strategies. Surgical treatment is an option for a defined patient population. PMID:12566335

  12. Momentum-based morphometric analysis with application to Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Chen, Jingyun; Khan, Ali R.; McKeown, Martin J.; Beg, Mirza F.

    2011-03-01

    We apply the initial momentum shape representation of diffeomorphic metric mapping from a template region of interest (ROI) to a given ROI as a morphometic marker in Parkinson's disease. We used a three-step segmentation-registrationmomentum process to derive feature vectors from ROIs in a group of 42 subjects consisting of 19 Parkinson's Disease (PD) subjects and 23 normal control (NC) subjects. Significant group differences between PD and NC subjects were detected in four basal ganglia structures including the caudate, putamen, thalamus and globus pallidus. The magnitude of regionally significant between-group differences detected ranged between 34-75%. Visualization of the different structural deformation pattern between-groups revealed that some parts of basal ganglia structure actually hypertrophy, presumably as a compensatory response to more widespread atrophy. Our results of both hypertrophy and atrophy in the same structures further demonstrate the importance of morphological measures as opposed to overall volume in the assessment of neurodegenerative disease.

  13. Glucocerebrosidase Involvement in Parkinson Disease and Other Synucleinopathies

    PubMed Central

    Almeida, Maria do Rosário

    2012-01-01

    Mutations in both copies (homozygous or compound heterozygous) of the gene encoding the lysosomal enzyme glucocerebrosidase, which cleaves the glycolipid glucocerebroside into glucose and ceramide cause Gaucher disease. However, multiple independent studies have also reported an association between GBA mutations and Parkinsonism with an increased frequency of heterozygous GBA mutations in various cohorts of patients with parkinsonism and other Lewy body disorders. Furthermore, GBA mutation carriers exhibit diverse parkinsonian phenotypes and present a diffuse pattern of Lewy body distribution in the cerebral cortex. This review provides an overview of the genetic basis for this association in various diseases with dysfunction of the central nervous system in which affected individuals developed Parkinsonian symptoms. The emerging clinical, pathological, and genetic studies in neuronal synucleinopathies suggest a common underlying mechanism in the etiology of these neurodegenerative disorders. PMID:22557990

  14. Exploring the link between glucocerebrosidase mutations and parkinsonism

    PubMed Central

    Westbroek, Wendy; Gustafson, Ann Marie; Sidransky, Ellen

    2012-01-01

    Clinical, genetic and pathological studies all demonstrate that mutations in glucocerebrosidase (GBA), which encodes the lysosomal enzyme deficient in Gaucher disease (GD), are an important and common risk factor for Parkinson disease (PD) and related disorders. Some patients with GD and Gaucher carriers develop parkinsonism. Furthermore, subjects with PD have a greatly increased frequency of GBA mutations. GBA mutation carriers exhibit diverse parkinsonian phenotypes, and have glucocerebrosidase-positive Lewy bodies. Although the mechanism for this association is unknown, we present several theories, including enhanced protein aggregation, prion transmission, lipid accumulation, and impaired autophagy, mitophagy or trafficking. Each has inherent limitations, and an unknown “second hit” might be essential. Elucidating the basis for this link will have important consequences and should provide new insights into lysosomal pathways and potential treatment strategies. PMID:21723784

  15. Mitochondrial DNA rearrangements in young onset parkinsonism: two case reports.

    PubMed

    Siciliano, G; Mancuso, M; Ceravolo, R; Lombardi, V; Iudice, A; Bonuccelli, U

    2001-11-01

    Parkinson's disease is a nosological entity of unknown origin for which, in some cases, a possible pathogenetic role for mitochondrial dysfunction has been postulated. Two young onset parkinsonian patients with mitochondrial DNA (mtDNA) deletions in skeletal muscle are reported on. Patient 1 also presented with increased blood creatine kinase and lactate concentrations and a family history which included a wide range of phenotypes affecting multiple systems. Patient 2 presented with multiple symmetric lipomatosis. Histopathological investigation showed ragged red fibres and COX negative fibres in muscle biopsies from both patients. The data support the hypothesis that mitochondrial DNA mutations may occur in some cases of parkinsonism, suggesting that a diagnosis of a mitochondrial disorder should be considered in the presence of consistent family history and clinical symptoms. PMID:11606686

  16. Meanings of feeling well among women with Parkinson's disease

    PubMed Central

    Olsson, Malin; Nilsson, Carina

    2015-01-01

    We conducted a qualitative inquiry to describe the meanings of feeling well as experienced by women with Parkinson's disease. Nine women were interviewed and we analysed the interviews using a reflective lifeworld approach based on phenomenological epistemology. We present the analysis as five constituents: the body as unnoticed; being able to move on; feeling joy by being connected; finding peace and harmony; and being the director of one's own life. Our findings can be used to understand and promote well-being among women with Parkinson's disease. In care meetings, knowledge about the lived and experienced health processes supports the women's striving to not let illness dominate their experience of daily life. PMID:26489404

  17. Parkinson's syndrome after closed head injury: a single case report.

    PubMed

    Doder, M; Jahanshahi, M; Turjanski, N; Moseley, I F; Lees, A J

    1999-03-01

    A 36 year old man, who sustained a skull fracture in 1984, was unconscious for 24 hours, and developed signs of Parkinson's syndrome 6 weeks after the injury. When assessed in 1995, neuroimaging disclosed a cerebral infarction due to trauma involving the left caudate and lenticular nucleus. Parkinson's syndrome was predominantly right sided, slowly progressive, and unresponsive to levodopa therapy. Reaction time tests showed slowness of movement initiation and execution with both hands, particularly the right. Recording of movement related cortical potentials suggested bilateral deficits in movement preparation. Neuropsychological assessment disclosed no evidence of major deficits on tests assessing executive function or working memory, with the exception of selective impairments on the Stroop and on a test of self ordered random number sequences. There was evidence of abulia. The results are discussed in relation to previous literature on basal ganglia lesions and the effects of damage to different points of the frontostriatal circuits. PMID:10084539

  18. Park sleep: a non-motor dominant Parkinson's disease phenotype.

    PubMed

    Canepa, Carlo

    2016-01-01

    A 69-year-old man was evaluated in our neurology department, for a presumed diagnosis of 'night-time seizures'; however, this diagnosis was quickly dismissed after the patient (and his wife) described how he 'acted out' and talked throughout his dreams, without any seizure-like activity. This problem had been present for ∼10 years. An EEG ruled out epilepsy. The patient also described a 10-year history of constipation, loss of smell and 'frequent collapses'. These symptoms fit in with the recently published criteria of 'prodromal Parkinson's Disease' and prompted a formal assessment for Parkinson's disease (PD). He had no tremor. A subtle festinating gait pattern and a 2-finger tremor in the right hand were noted. The diagnosis of PD was confirmed by a dopamine transporter scan. Clinically, this is one-Park sleep: rapid eye movement sleep behaviour disorder subtype-of 7 different non-motor dominant PD phenotypes recently described. PMID:27284098

  19. Bumetanide to Treat Parkinson Disease: A Report of 4 Cases.

    PubMed

    Damier, Philippe; Hammond, Constance; Ben-Ari, Yeheskel

    2016-01-01

    Relying on recent experimental data in 2 animal models of Parkinson disease (PD), we have tested the effects of the loop diuretic bumetanide as an add-on treatment to dopaminergic drugs in 4 volunteered patients with PD using the Unified Parkinson's Disease Rating Scale. Bumetanide is a specific antagonist of the chloride importer NKCC1 (sodium/potassium/chloride cotransporter isoform 1) that ameliorates neuronal inhibition by reducing intracellular chloride levels in a variety of pathological conditions. Bumetanide is however not labeled for use in PD. We report an improvement of PD motor symptoms in the 4 patients treated with bumetanide (5 mg/d for 2 months). Bumetanide also improved gait and freezing in 2 of these patients. Our results suggest that bumetanide is well tolerated and call for double-blind, placebo-controlled, randomized trials to confirm the therapeutic efficacy of bumetanide. PMID:26757306

  20. Fatigue in Parkinson's disease: report from a mutidisciplinary symposium

    PubMed Central

    Friedman, Joseph H; Beck, James C; Chou, Kelvin L; Clark, Gracia; Fagundes, Christopher P; Goetz, Christopher G; Herlofson, Karen; Kluger, Benzi; Krupp, Lauren B; Lang, Anthony E; Lou, Jao-Shin; Marsh, Laura; Newbould, Anne; Weintraub, Daniel

    2016-01-01

    Fatigue is a severe problem for many people living with Parkinson's disease (PD). Best estimates suggest that more than 50% of patients experience this debilitating symptom. Little is known about its etiology or treatment, making the understanding of fatigue a true unmet need. As part of the Parkinson's Disease Foundation Community Choice Research Program, patients, caregivers, and scientists attended a symposium on fatigue on 16 and 17 October 2014. We present a summary of that meeting, reviewing what is known about the diagnosis and treatment of fatigue, its physiology, and what we might learn from multiple sclerosis (MS), depression, and cancer—disorders in which fatigue figures prominently too. We conclude with focused recommendations to enhance our understanding and treatment of this prominent problem in PD. PMID:27239558

  1. New concepts in the pathogenesis and presentation of Parkinson's disease.

    PubMed

    Sauerbier, Anna; Qamar, Mubasher A; Rajah, Thadshani; Chaudhuri, K Ray

    2016-08-01

    Parkinson's disease (PD) was first described by James Parkinson in 1817. He noted the complex nature of this condition and that non-motor symptoms (NMS) underpinned the classic motor symptoms of PD. The concept of what PD is has therefore undergone substantial changes and it is now recognised that PD is a combined motor and non-motor syndrome and NMS are present during the prodromal phase of PD, starting up to 20 years before the first clinical motor signs emerge. PD may originate from pathology in the gut, olfactory bulb and lower brainstem rather than in the substantia nigra. Complex phenotypes of PD may exist where clinical NMS overshadow motor features. Therapy needs to be adjusted based on motor and non-motor loads, ideally using validated tools. Recently, a multimodal biomarker battery in PD has emerged and might play an important role in the future. PMID:27481383

  2. Mitochondria-Targeted Protective Compounds in Parkinson's and Alzheimer's Diseases

    PubMed Central

    Fernández-Moriano, Carlos; González-Burgos, Elena; Gómez-Serranillos, M. Pilar

    2015-01-01

    Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways; their most highlighted functions include cellular energy generation in the form of adenosine triphosphate (ATP), regulation of cellular calcium homeostasis, balance between ROS production and detoxification, mediation of apoptosis cell death, and synthesis and metabolism of various key molecules. Consistent evidence suggests that mitochondrial failure is associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinson's disease and Alzheimer's disease. Mitochondria-targeted protective compounds that prevent or minimize mitochondrial dysfunction constitute potential therapeutic strategies in the prevention and treatment of these central nervous system diseases. This paper provides an overview of the involvement of mitochondrial dysfunction in Parkinson's and Alzheimer's diseases, with particular attention to in vitro and in vivo studies on promising endogenous and exogenous mitochondria-targeted protective compounds. PMID:26064418

  3. [Gait disorders in Parkinson's disease: and pathophysiological approaches].

    PubMed

    Moreau, C; Cantiniaux, S; Delval, A; Defebvre, L; Azulay, J-P

    2010-02-01

    Gait disorders and axial symptoms are the main therapeutic challenges in advanced Parkinson's disease (PD). Gait disorders in PD are characterized by spatial and temporal dysfunction. Gait hypokinesia is the first to appear and is responsible for the decrease in velocity. A good sensitivity to the levodopa is well established. Morris et al. [Morris ME, Iansek R, Matyas TA, Summers JJ. Ability to modulate walking cadence remains intact in Parkinson's disease. J Neurol Neurosurg Psychiatry 1994a;57(12):1532-4; Morris ME, Iansek R, Matyas TA, Summers JJ. The pathogenesis of gait hypokinesia in Parkinson's disease. Brain 1994b;117(Pt. 5):1169-81; Morris ME, Iansek R, Matyas TA, Summers JJ. Stride length regulation in Parkinson's disease. Brain 1996;119:551-68] demonstrated that the ability to modulate walking cadence remains intact in PD, and could correspond to a compensatory mechanism. More advanced disease stages of the disease are characterized by abnormal temporal parameters (such as stride length variability, stride time variability and cadence elevation) which are unresponsive to levodopa therapy and may be correlated with the occurrence of falls and freezing of gait (FOG). Lastly, postural instability also results in falls and is poorly responsive to levodopa. A link between gait impairment and frontal disorders has recently been suggested. After a few years of evolution, paradoxical episodic phenomena are described: festination ("hastening gait" with rapid small, short steps) and FOG (involuntary and sudden cessation of gait). Both symptoms are often incapacitating for PD patients, because of their resultant loss of independence and their poor response to levodopa therapy. Kinematical studies of FOG revealed a decrease in velocity, stride length and an exponential increase in cadence, prior to a FOG episode. New approaches (functional MRI, wavelets...) should offer new perspectives concerning these disabling symptoms. PMID:19616816

  4. Co-occurrence of multiple sclerosis and Parkinson disease

    PubMed Central

    Shaygannejad, Vahid; Shirmardi, Maryam; Dehghani, Leila; Maghzi, Helia

    2016-01-01

    Parkinson disease (PD) is a neurodegenerative disease of the central nervous system (CNS) with the highest prevalence in adults over 60 years of age On the other hand multiple sclerosis (MS), which mostly affects individuals between 20 and 40 years of age, is another neurodegenerative and autoimmune disease of the CNS, however, less common than PD. Here we aim to report the case of a 39-year-old woman, who developed PD 18 years after diagnosis of MS. PMID:27195248

  5. Co-occurrence of multiple sclerosis and Parkinson disease.

    PubMed

    Shaygannejad, Vahid; Shirmardi, Maryam; Dehghani, Leila; Maghzi, Helia

    2016-01-01

    Parkinson disease (PD) is a neurodegenerative disease of the central nervous system (CNS) with the highest prevalence in adults over 60 years of age On the other hand multiple sclerosis (MS), which mostly affects individuals between 20 and 40 years of age, is another neurodegenerative and autoimmune disease of the CNS, however, less common than PD. Here we aim to report the case of a 39-year-old woman, who developed PD 18 years after diagnosis of MS. PMID:27195248

  6. Parkinson risk in idiopathic REM sleep behavior disorder

    PubMed Central

    Postuma, Ronald B.; Gagnon, Jean-Francois; Bertrand, Josie-Anne; Génier Marchand, Daphné

    2015-01-01

    Objective: To precisely delineate clinical risk factors for conversion from idiopathic REM sleep behavior disorder (RBD) to Parkinson disease, dementia with Lewy bodies, and multiple system atrophy, in order to enable practical planning and stratification of neuroprotective trials against neurodegenerative synucleinopathy. Methods: In a 10-year prospective cohort, we tested prodromal Parkinson disease markers in 89 patients with idiopathic RBD. With Kaplan-Meier analysis, we calculated risk of neurodegenerative synucleinopathy, and using Cox proportional hazards, tested the ability of prodromal markers to identify patients at higher disease risk. By combining predictive markers, we then designed stratification strategies to optimally select patients for definitive neuroprotective trials. Results: The risk of defined neurodegenerative synucleinopathy was high: 30% developed disease at 3 years, rising to 66% at 7.5 years. Advanced age (hazard ratio [HR] = 1.07), olfactory loss (HR = 2.8), abnormal color vision (HR = 3.1), subtle motor dysfunction (HR = 3.9), and nonuse of antidepressants (HR = 3.5) identified higher risk of disease conversion. However, mild cognitive impairment (HR = 1.8), depression (HR = 0.63), Parkinson personality, treatment with clonazepam (HR = 1.3) or melatonin (HR = 0.55), autonomic markers, and sex (HR = 1.37) did not clearly predict clinical neurodegeneration. Stratification with prodromal markers increased risk of neurodegenerative disease conversion by 200%, and combining markers allowed sample size reduction in neuroprotective trials by >40%. With a moderately effective agent (HR = 0.5), trials with fewer than 80 subjects per group can demonstrate definitive reductions in neurodegenerative disease. Conclusions: Using stratification with simply assessed markers, it is now not only possible, but practical to include patients with RBD in neuroprotective trials against Parkinson disease, multiple system atrophy, and dementia with Lewy bodies

  7. Machine learning on Parkinson's disease? Let's translate into clinical practice.

    PubMed

    Cerasa, Antonio

    2016-06-15

    Machine learning techniques represent the third-generation of clinical neuroimaging studies where the principal interest is not related to describe anatomical changes of a neurological disorder, but to evaluate if a multivariate approach may use these abnormalities to predict the correct classification of previously unseen clinical cohort. In the next few years, Machine learning will revolutionize clinical practice of Parkinson's disease, but enthusiasm should be turned down before removing some important barriers. PMID:26743974

  8. Motor Skill Learning, Retention, and Control Deficits in Parkinson's Disease

    PubMed Central

    Pendt, Lisa Katharina; Reuter, Iris; Müller, Hermann

    2011-01-01

    Parkinson's disease, which affects the basal ganglia, is known to lead to various impairments of motor control. Since the basal ganglia have also been shown to be involved in learning processes, motor learning has frequently been investigated in this group of patients. However, results are still inconsistent, mainly due to skill levels and time scales of testing. To bridge across the time scale problem, the present study examined de novo skill learning over a long series of practice sessions that comprised early and late learning stages as well as retention. 19 non-demented, medicated, mild to moderate patients with Parkinson's disease and 19 healthy age and gender matched participants practiced a novel throwing task over five days in a virtual environment where timing of release was a critical element. Six patients and seven control participants came to an additional long-term retention testing after seven to nine months. Changes in task performance were analyzed by a method that differentiates between three components of motor learning prominent in different stages of learning: Tolerance, Noise and Covariation. In addition, kinematic analysis related the influence of skill levels as affected by the specific motor control deficits in Parkinson patients to the process of learning. As a result, patients showed similar learning in early and late stages compared to the control subjects. Differences occurred in short-term retention tests; patients' performance constantly decreased after breaks arising from poorer release timing. However, patients were able to overcome the initial timing problems within the course of each practice session and could further improve their throwing performance. Thus, results demonstrate the intact ability to learn a novel motor skill in non-demented, medicated patients with Parkinson's disease and indicate confounding effects of motor control deficits on retention performance. PMID:21760898

  9. Epidemiology of Parkinson disease in the city of Kolkata, India

    PubMed Central

    Das, S.K.; Misra, A.K.; Ray, B.K.; Hazra, A.; Ghosal, M.K.; Chaudhuri, A.; Roy, T.; Banerjee, T.K.; Raut, D.K.

    2010-01-01

    Objective: No well-designed longitudinal study on Parkinson disease (PD) has been conducted in India. Therefore, we planned to determine the prevalence, incidence, and mortality rates of PD in the city of Kolkata, India, on a stratified random sample through a door-to-door survey. Method: This study was undertaken between 2003 to 2007 with a validated questionnaire by a team consisting of 4 trained field workers in 3 stages. Field workers screened the cases, later confirmed by a specialist doctor. In the third stage, a movement disorders specialist undertook home visits and reviewed all surviving cases after 1 year from last screening. Information on death was collected through verbal autopsy. A nested case-control study (1:3) was also undertaken to determine putative risk factors. The rates were age adjusted to the World Standard Population. Result: A total population of 100,802 was screened. The age-adjusted prevalence rate (PR) and average annual incidence rate were 52.85/100,000 and 5.71/100,000 per year, respectively. The slum population showed significantly decreased PR with age compared with the nonslum population. The adjusted average annual mortality rate was 2.89/100,000 per year. The relative risk of death was 8.98. The case-control study showed that tobacco chewing protected and hypertension increased PD occurrence. Conclusion: This study documented lower prevalence and incidence of PD as compared with Caucasian and a few Oriental populations. The mortality rates were comparable. The decreased age-specific PR among slum populations and higher relative risk of death need further probing. GLOSSARY AAIR = average annual incidence rate; AAMR = average annual mortality rate; CI = confidence interval; FSQ = family screening questionnaire; ICC = intraclass correlation coefficient; IR = incidence rate; MD = movement disorder; NSSO = National Sample Survey Organization; OR = odds ratio; PD = Parkinson disease; PPS = parkinsonism plus syndrome; PR = prevalence

  10. Multi-center analysis of glucocerebrosidase mutations in Parkinson disease

    PubMed Central

    Sidransky, Ellen; Nalls, Michael A.; Aasly, Jan O.; Aharon-Peretz, Judith; Annesi, Grazia; Barbosa, Egberto Reis; Bar-Shira, Anat; Berg, Daniela; Bras, Jose; Brice, Alexis; Chen, Chiung-Mei; Clark, Lorraine N.; Condroyer, Christel; De Marco, Elvira Valeria; Dürr, Alexandra; Eblan, Michael J.; Fahn, Stanley; Farrer, Matthew; Fung, Hon-Chung; Gan-Or, Ziv; Gasser, Thomas; Gershoni-Baruch, Ruth; Giladi, Nir; Griffith, Alida; Gurevich, Tanya; Januario, Cristina; Kropp, Peter; Lang, Anthony E.; Lee-Chen, Guey-Jen; Lesage, Suzanne; Marder, Karen; Mata, Ignacio F.; Mirelman, Anat; Mitsui, Jun; Mizuta, Ikuko; Nicoletti, Giuseppe; Oliveira, Catarina; Ottman, Ruth; Orr-Urtreger, Avi; Pereira, Lygia V.; Quattrone, Aldo; Rogaeva, Ekaterina; Rolfs, Arndt; Rosenbaum, Hanna; Rozenberg, Roberto; Samii, Ali; Samaddar, Ted; Schulte, Claudia; Sharma, Manu; Singleton, Andrew; Spitz, Mariana; Tan, Eng-King; Tayebi, Nahid; Toda, Tatsushi; Troiano, André; Tsuji, Shoji; Wittstock, Matthias; Wolfsberg, Tyra G.; Wu, Yih-Ru; Zabetian, Cyrus P.; Zhao, Yi; Ziegler, Shira G.

    2010-01-01

    Background Recent studies indicate an increased frequency of mutations in the gene for Gaucher disease, glucocerebrosidase (GBA), among patients with Parkinson disease. An international collaborative study was conducted to ascertain the frequency of GBA mutations in ethnically diverse patients with Parkinson disease. Methods Sixteen centers participated, including five from the Americas, six from Europe, two from Israel and three from Asia. Each received a standard DNA panel to compare genotyping results. Genotypes and phenotypic data from patients and controls were analyzed using multivariate logistic regression models and the Mantel Haenszel procedure to estimate odds ratios (ORs) across studies. The sample included 5691 patients (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews). Results All 16 centers could detect GBA mutations, L444P and N370S, and the two were found in 15.3% of Ashkenazi patients with Parkinson disease (ORs = 4.95 for L444P and 5.62 for N370S), and in 3.2% of non-Ashkenazi patients (ORs = 9.68 for L444P and 3.30 for N370S). GBA was sequenced in 1642 non-Ashkenazi subjects, yielding a frequency of 6.9% for all mutations, demonstrate that limited mutation screens miss half the mutant alleles. The presence of any GBA mutation was associated with an OR of 5.43 across studies. Clinically, although phenotypes varied, subjects with a GBA mutation presented earlier, and were more likely to have affected relatives and atypical manifestations. Conclusion Data collected from sixteen centers demonstrate that there is a strong association between GBA mutations and Parkinson disease. PMID:19846850

  11. Deep-brain stimulator and control of Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Varadan, Vijay K.; Harbaugh, Robert; Abraham, Jose K.

    2004-07-01

    The design of a novel feedback sensor system with wireless implantable polymer MEMS sensors for detecting and wirelessly transmitting physiological data that can be used for the diagnosis and treatment of various neurological disorders, such as Parkinson's disease, epilepsy, head injury, stroke, hydrocephalus, changes in pressure, patient movements, and tremors is presented in this paper. The sensor system includes MEMS gyroscopes, accelerometers, and pressure sensors. This feedback sensor system focuses on the development and integration of implantable systems with various wireless sensors for medical applications, particularly for the Parkinson's disease. It is easy to integrate and modify the sensor network feed back system for other neurological disorders mentioned above. The monitoring and control of tremor in Parkinson's disease can be simulated on a skeleton via wireless telemetry system communicating with electroactive polymer actuator, and microsensors attached to the skeleton hand and legs. Upon sensing any abnormal motor activity which represent the characteristic rhythmic motion of a typical Parkinson's (PD) patient, these sensors will generate necessary control pulses which will be transmitted to a hat sensor system on the skeleton head. Tiny inductively coupled antennas attached to the hat sensor system can receive these control pulses, demodulate and deliver it to actuate the parts of the skeleton to control the abnormal motor activity. This feedback sensor system can further monitor and control depending on the amplitude of the abnormal motor activity. This microsystem offers cost effective means of monitoring and controlling of neurological disorders in real PD patients. Also, this network system offers a remote monitoring of the patients conditions without visiting doctors office or hospitals. The data can be monitored using PDA and can be accessed using internet (or cell phone). Cellular phone technology will allow a health care worker to be

  12. [Contralateral and ipsilateral repetitive transcranial magnetic stimulation in Parkinson patients].

    PubMed

    de Groot, M; Hermann, W; Steffen, J; Wagner, A; Grahmann, F

    2001-12-01

    In seven women and two men with Parkinson's disease, Hoehn and Yahr stage 1 or 2, the effect of repetitive transcranial magnetic stimulation (rTMS) was evaluated. Primary endpoint outcome measure was the changing of the motor items of the Unified Parkinson's Disease Rating Scale (subscale III of UP-DRS) 24 h after stimulation. Kinesiologic tests and writing samples were secondary outcome measures. After discontinuing all medication, stimulation was performed with 5 Hz at 90% of the motor threshold over the primary motor cortex of the more affected. There were 2250 stimuli applied, divided into 15 trains at intervals of 10 s. The identical treatment of the opposite side served as control treatment. Only treatment of the more affected side resulted in a significant improvement of the clinical symptoms of 46% as assessed by the UPDRS (p < 0.02). This effectiveness differed significantly from the control treatment (21%, p < 0.02). The kinesiological testing did not show any significant speeding of movements (p > 0.05). Some patients showed a normalisation of the previously disturbed handwriting specimen. These data confirm the previous observation that rTMS of primary motor regions leads to at least temporary clinical improvement of symptoms in patients with Parkinson's disease. PMID:11789438

  13. Validity of spiral analysis in early Parkinson's disease.

    PubMed

    Saunders-Pullman, Rachel; Derby, Carol; Stanley, Kaili; Floyd, Alicia; Bressman, Susan; Lipton, Richard B; Deligtisch, Amanda; Severt, Lawrence; Yu, Qiping; Kurtis, Mónica; Pullman, Seth L

    2008-03-15

    Spiral analysis is an objective, easy to administer noninvasive test that has been proposed to measure motor dysfunction in Parkinson disease (PD). We compared overall Unified Parkinson Disease Rating Scale Part III scores to selected indices derived from spiral analysis in seventy-four patients with early PD (mean duration of disease 2.4 +/- 1.7 years, mean age 61.5 +/- 9.7 years). Of the spiral indices, degree of severity, first order zero crossing, second order smoothness, and mean speed were best correlated with total motor Unified Parkinson's Disease Rating Scale (UPDRS) score (all P < 0.01), and these indices showed a gradient across worsening tertiles of UPDRS (P < 0.05). Spiral indices also correlated with UPDRS ratings for the worst side and worst arm scores as well. The domains of bradykinesia, rigidity, and action tremor were correlated with first order crossing, second order smoothness, and mean speed, where as rest tremor was most highly correlated with degree of severity. This suggests that the spiral analysis may supplement motor assessment in PD, although further analysis of spiral metrics, a larger sample and longitudinal data should be evaluated. PMID:18074362

  14. Neurorehabilitation for Parkinson's disease: Future perspectives for behavioural adaptation.

    PubMed

    Ekker, Merel S; Janssen, Sabine; Nonnekes, Jorik; Bloem, Bastiaan R; de Vries, Nienke M

    2016-01-01

    Parkinson's disease is a common neurodegenerative disorder, resulting in both motor and non-motor symptoms that significantly reduce quality of life. Treatment consists of both pharmaceutical and non-pharmaceutical treatment approaches. Neurorehabilitation is an important non-pharmaceutical treatment approach, and a prime component of this is formed by the training of behavioural adaptations that can assist patients to cope better with their motor and non-motor symptoms. Optimal delivery of neurorehabilitation requires a tailor-made, personalized approach. In this review we discuss the great potential for growth in the field of neurorehabilitation. Specifically, we will focus on four relatively new developments: visual rehabilitation (because Parkinson patients are very dependent on optimal vision); cueing delivered by wearable devices (allowing for objective, continuous, and quantitative detection of mobility problems, such that cueing can be delivered effectively in an on-demand manner - i.e., with external cues being delivered only at a time when they are needed most); exergaming (to promote compliance with exercise programs); and telemedicine (allowing for delivery of expert rehabilitation advice to the patient's own home). Evidence in these new fields is growing, based on good clinical trials, fuelling hope that state-of-the-art neurorehabilitation can make a real impact on improving the quality of life of patients affected by Parkinson's disease. PMID:26362955

  15. Hypothalamic digoxin-mediated model for Parkinson's disease.

    PubMed

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-04-01

    The isoprenoid pathway produces four key metabolites important in cellular function--digoxin (endogenous membrane Na(+)-K+ ATPase inhibitor), dolichol (important in N-glycosylation of proteins), ubiquinone (free-radical scavenger), and cholesterol (component of cellular membranes). This study assessed the changes in the isoprenoid pathway and the consequences of its dysfunction in Parkinson's disease (PD). There was an elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol levels, and a reduction in serum magnesium, RBC membrane Na(+)-K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine, and quinolinic acid were elevated, while tyrosine, morphine, dopamine, and noradrenaline were decreased. The total serum glycosaminoglycans (GAG) and glycosaminoglycan fractions (except chondroitin sulphates and hyaluronic acid), the activity of GAG degrading enzymes, carbohydrate residues of serum glycoproteins, the activity of glycohydrolase-beta galactosidase, and serum glycolipids were elevated. HDL cholesterol was reduced and free fatty acids increased. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins and cholesterol were reduced, while phospholipid was increased. The activity of all serum free-radical scavenging enzymes, concentration of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin decreased significantly in PD, while the concentration of serum lipid peroxidation products and nitric oxide increased. A dysfunctional isoprenoid pathway and related cascade are important in the pathogenesis of Parkinson's disease. A hypothalamic digoxin mediated model for Parkinson's disease is also postulated. PMID:12856480

  16. Why we should study gait initiation in Parkinson's disease.

    PubMed

    Delval, A; Tard, C; Defebvre, L

    2014-01-01

    The gait initiation process is of particular interest in Parkinson's disease because it combines motor and cognitive components of movement preparation (referred to as anticipatory postural adjustments) and movement execution (the step by itself). Moreover, gait initiation in Parkinson's disease is often affected by motor blocks (a subtype of the "freezing of gait" phenomenon). Gait initiation disturbances in Parkinson's disease include delayed release of anticipatory postural adjustments, hypokinetic anticipatory postural adjustments (reduced scaling) and bradykinetic anticipatory postural adjustments (abnormal timing). The most extreme form is freezing of gait with sometimes the absence of anticipatory postural adjustments. Other phenomena can be also described in some freezing patients (such as multiple anticipatory postural adjustments, described clinically as "knee trembling"). The fact that emotion, attention, external triggers and dopaminergic drugs can all modify this motor program suggests the existence of a complex pathophysiological mechanism that involves not only locomotor networks but also cortical areas and the basal ganglia system. Abnormal coupling between standing posture and anticipatory postural adjustments and between the latter and step execution appears to be a crucial part of the pathophysiological mechanism. Although external cueing appears to be of interest, few studies have provided evidence of the efficacy of various rehabilitation methods in routine care. PMID:24502907

  17. Subcortical evoked activity and motor enhancement in Parkinson's disease

    PubMed Central

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S.; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L.; Aziz, Tipu; Brown, Peter

    2016-01-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of ‘paradoxical kinesis’ in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus – a key component of the reticular activating system – provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an ‘energizing’ influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. PMID:26687971

  18. A central executive deficit in patients with Parkinson's disease.

    PubMed Central

    Dalrymple-Alford, J C; Kalders, A S; Jones, R D; Watson, R W

    1994-01-01

    Eight patients with Parkinson's disease and eight matched controls were tested for concurrent task performance to examine whether Parkinson's disease produces deficits in the coordinating and integrating function of the central executive component of Baddeley's working memory model. Consistent with this prediction, the patients showed a significant decline in performance on a random pursuit tracking task while recalling digit span forward sequences, whereas the controls showed no such change. Performance on the component pursuit and digit span tasks, which did not differ between groups, was equated across subjects by varying the size of a target square and by using individual subjects' digit spans. The patient group also produced poorer word fluency scores and reported higher levels of depression, but there was no significant impairment on the Wisconsin card sort test. There was no association between dual task performance and any psychometric measure, target size, or disease related variables. Baddeley's working memory model is advantageous in providing a rich conceptual basis to explore and characterise cognitive abilities in patients with Parkinson's disease. PMID:8158188

  19. Anatomic and physiological considerations in pallidotomy for Parkinson's disease.

    PubMed

    Dogali, M; Berić, A; Sterio, D; Eidelberg, D; Fazzini, E; Takikawa, S; Samelson, D R; Devinsky, O; Kolodny, E H

    1994-01-01

    Our ongoing study of central pallidotomy for the control of Parkison's disease in selected patients has provided the opportunity to explore the topographical and somatotopic organization of the human globus pallidus. Utilizing microelectrode techniques we have obtained recordings which were correlated with data from MPTP-parkinsonian primates. In addition, we performed pre- and postoperative FDG/PET scans in these patients. Our studies reveal similarities between the MPTP-parkisonian primate model and human Parkinson's disease in terms of physiological recordings and responses. However, we have encountered significant differences between dominant and nondominant hemisphere representations, particularly for the hand, in the human. In addition, our PET studies confirmed, as in previous parkinsonian primate models, glucose hypermetabolism in the lenticular area of Parkinson's disease patients. This hypermetabolism is dramatically altered by creation of a lesion in the globus pallidus medialis. This is demonstrated by follow-up PET scans which reveal not only a decrease in metabolism of the operated lenticular region, but also in the frontal cortical projections. These combined observations of the cellular activity in globus pallidus and the observed changes in PET metabolism support the selection of the pallidum for lesioning and control of Parkinson's disease, and offer insight into the underlying physiology of this disorder. The above physiological and PET data will be clinically correlated with our ongoing series of 35+ patients. PMID:7631089

  20. Neurophysiological properties of pallidal neurons in Parkinson's disease.

    PubMed

    Sterio, D; Berić, A; Dogali, M; Fazzini, E; Alfaro, G; Devinsky, O

    1994-05-01

    Neuronal properties of the human globus pallidus (GP) are not known. Since GP is the major output of the basal ganglia, it may be involved in the pathophysiology of Parkinson's disease. We studied 12 patients with medically resistant Parkinson's disease by using single cell recording of the GP during stereotaxic pallidotomy to define neuronal firing rate and its modulation during active and passive movements. Different frequency and pattern of single cell activity was found in globus pallidus externus compared with globus pallidus internus. Discharge rates of 19% of GP cells were modulated by passive contralateral movements. Pallidal units were most often related solely to single joint movement. Different patterns of activity in relation to the two different movements of the same joint were often observed. We identified somatotopically arranged cell clusters that alter discharge rate with related movements. These findings suggest at least a partial somatotopic organization of the human GP and similarity with experimental results in both healthy and MPTP monkeys, providing a rationale for surgical or pharmacological targeting of GP for treating Parkinson's disease. PMID:8179304

  1. Great expectations: the placebo effect in Parkinson's disease.

    PubMed

    Lidstone, Sarah Christine

    2014-01-01

    Our understanding of the neural mechanisms underlying the placebo effect has increased exponentially in parallel with the advances in brain imaging. This is of particular importance in the field of Parkinson's disease, where clinicians have described placebo effects in their patients for decades. Significant placebo effects have been observed in clinical trials for medications as well as more invasive surgical trials including deep-brain stimulation and stem-cell implantation. In addition to placebo effects occurring as a byproduct of randomized controlled trials, investigation of the placebo effect itself in the laboratory setting has further shown the capacity for strong placebo effects within this patient population. Neuroimaging studies have demonstrated that placebos stimulate the release of dopamine in the striatum of patients with Parkinson's disease and can alter the activity of dopamine neurons using single-cell recording. When taken together with the findings from other medical conditions discussed elsewhere in this publication, a unified mechanism for the placebo effect in Parkinson's disease is emerging that blends expectation-induced neurochemical changes and disease-specific nigrostriatal dopamine release. PMID:25304530

  2. Missense dopamine transporter mutations associate with adult parkinsonism and ADHD

    PubMed Central

    Hansen, Freja H.; Skjørringe, Tina; Yasmeen, Saiqa; Arends, Natascha V.; Sahai, Michelle A.; Erreger, Kevin; Andreassen, Thorvald F.; Holy, Marion; Hamilton, Peter J.; Neergheen, Viruna; Karlsborg, Merete; Newman, Amy H.; Pope, Simon; Heales, Simon J.R.; Friberg, Lars; Law, Ian; Pinborg, Lars H.; Sitte, Harald H.; Loland, Claus; Shi, Lei; Weinstein, Harel; Galli, Aurelio; Hjermind, Lena E.; Møller, Lisbeth B.; Gether, Ulrik

    2014-01-01

    Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies. PMID:24911152

  3. Parkinson's Disease Sleep Scale 2: application in an Italian population.

    PubMed

    Arnaldi, Dario; Cordano, Christian; De Carli, Fabrizio; Accardo, Jennifer; Ferrara, Michela; Picco, Agnese; Tamburini, Tiziano; Brugnolo, Andrea; Abbruzzese, Giovanni; Nobili, Flavio

    2016-02-01

    Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's α: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients. PMID:26520846

  4. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    PubMed

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging. PMID:26962957

  5. Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression.

    PubMed

    Andersen, Anders H; Smith, Charles D; Slevin, John T; Kryscio, Richard J; Martin, Catherine A; Schmitt, Frederick A; Blonder, Lee X

    2015-01-01

    Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients. PMID:26793404

  6. Dopaminergic modulation of memory and affective processing in Parkinson depression

    PubMed Central

    Blonder, Lee X.; Slevin, John T.; Kryscio, Richard J.; Martin, Catherine A.; Andersen, Anders H.; Smith, Charles D.; Schmitt, Frederick A.

    2013-01-01

    Depression is common in Parkinson’s disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson’s disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson’s disease participated. Ten of these patients were depressed according to DSM IV criteria. Results revealed a statistically significant interaction between depression and medication status on three measures of verbal memory and a facial affect naming task. In all cases, depressed Parkinson’s patients performed significantly more poorly while on dopaminergic medication than while off. The opposite pattern emerged for the non-depressed Parkinson’s group. The administration of dopaminergic medication to depressed Parkinson patients may carry unintended risks. PMID:23838419

  7. Characteristics of diadochokinesis in Parkinson's Disease and Multiple Sclerosis

    NASA Astrophysics Data System (ADS)

    Tjaden, Kris; Watling, Elizabeth

    2002-05-01

    The current study applies a quantitative, acoustic analysis procedure for the study of rapid syllable productions outlined by Kent and colleagues [R. D. Kent et al., J. Med. Sp. Lang. Path. 7, 83-90 (1999)] to syllables produced by speakers with Parkinson's Disease and Multiple Sclerosis. Neurologically healthy talkers will be studied for comparison purposes. Acoustic measures will be reported for syllable repetitions of /p schwa/, /t schwa/, and /k schwa/. Temporal measures will include syllable duration, syllable rate, and stop gap duration. The energy envelope of syllable repetitions will be quantified using measures of rms amplitude minima and maxima. Acoustic measures will be contrasted to determine the extent to which acoustic profiles of diadochokinesis distinguish hypokinetic dysarthria associated with Parkinson's Disease, ataxic dysarthria secondary to Multiple Sclerosis, and spastic dysarthria secondary to Multiple Sclerosis. It also is of interest to determine whether speakers with Parkinson's Disease and Multiple Sclerosis judged to be nondysarthric via perceptual analyses also demonstrate objective, acoustic profiles of diadochokinesis that are within normal limits. [Work supported by NIH.

  8. Subcortical evoked activity and motor enhancement in Parkinson's disease.

    PubMed

    Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Khan, Sadaquate; Javed, Shazia; Gill, Steven S; Ashkan, Keyoumars; Akram, Harith; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L; Aziz, Tipu; Brown, Peter

    2016-03-01

    Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus - a key component of the reticular activating system - provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an 'energizing' influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease. PMID:26687971

  9. The association between ß-glucocerebrosidase mutations and parkinsonism

    PubMed Central

    Swan, Matthew; Saunders-Pullman, Rachel

    2013-01-01

    Mutations in the ß-glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme ß-glucocerebrosidase, have traditionally been implicated in Gaucher disease, an autosomal-recessive lyososomal storage disorder. Yet the past two decades have yielded an explosion of epidemiological and basic-science evidence linking mutations in GBA with the development of Parkinson disease as well. Although the specific contribution of mutant GBA to the pathogenesis of parkinsonism remains unknown, evidence suggests both loss of function and toxic gain-of-function by abnormal ß-glucocerebrosidase may be important, and a close relationship between ß-glucocerebrosidase and α-synuclein. Furthermore, multiple lines of evidence suggest that while GBA-associated PD closely mimics idiopathic PD (IPD), it may present at a younger age, and is more frequently complicated by cognitive dysfunction. Understanding the clinical association between GBA and PD, and the relationship between ß-glucocerebrosidase and α-synuclein, may enhance understanding of the pathogenesis of IPD, improve prognostication and treatment of GBA carriers with parkinsonism, and may furthermore inform therapies for IPD not due to GBA mutations. PMID:23812893

  10. Unraveling a new circuitry for sleep regulation in Parkinson's disease.

    PubMed

    Targa, Adriano D S; Rodrigues, Lais S; Noseda, Ana Carolina D; Aurich, Mariana F; Andersen, Monica L; Tufik, Sergio; da Cunha, Cláudio; Lima, Marcelo M S

    2016-09-01

    Sleep disturbances are among the most disabling non-motor symptoms in Parkinson's disease. The pedunculopontine tegmental nucleus and basal ganglia are likely involved in these dysfunctions, as they are affected by neurodegeneration in Parkinson's disease and have a role in sleep regulation. To investigate this, we promoted a lesion in the pedunculopontine tegmental nucleus or substantia nigra pars compacta of male rats, followed by 24 h of REM sleep deprivation. Then, we administrated a dopaminergic D2 receptor agonist, antagonist or vehicle directly in the striatum. After a period of 24 h of sleep-wake recording, we observed that the ibotenic acid infusion in the pedunculopontine tegmental nucleus blocked the so-called sleep rebound effect mediated by REM sleep deprivation, which was reversed by striatal D2 receptors activation. Rotenone infusion in the substantia nigra pars compacta also blocked the sleep rebound, however, striatal D2 receptors activation did not reverse it. In addition, rotenone administration decreased the time spent in NREM sleep, which was corroborated by positive correlations between dopamine levels in both substantia nigra pars compacta and striatum and the time spent in NREM sleep. These findings suggest a new circuitry for sleep regulation in Parkinson's disease, involving the triad composed by pedunculopontine nucleus, substantia nigra pars compacta and striatum, evidencing a potential therapeutic target for the sleep disturbances associated to this pathology. PMID:27091486

  11. A controlled, longitudinal study of dementia in Parkinson's disease.

    PubMed Central

    Biggins, C A; Boyd, J L; Harrop, F M; Madeley, P; Mindham, R H; Randall, J I; Spokes, E G

    1992-01-01

    Serial assessments of cognition, mood, and disability were carried out at nine month intervals over a 54 month period on a cohort of 87 patients with Parkinson's disease (PD) and a matched cohort of 50 control subjects. Dementia was diagnosed from data by rigorously applying DSM-III-R criteria. Initially, 6% (5/87) PD patients were demented, compared with none of the 50 control subjects. A further 10 PD patients met the dementia criteria during the follow up period; this was equivalent, with survival analysis, to a cumulative incidence of 19%. With the number of person years of observation as the denominator, the incidence was 47.6/1000 person years of observation. None of the control subjects fulfilled dementia criteria during the follow up period. The patients with PD who became demented during follow up were older at onset of Parkinson's disease than patients who did not become demented, had a longer duration of Parkinson's disease, and were older at inclusion to the study. PMID:1640232

  12. Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression

    PubMed Central

    Andersen, Anders H.; Smith, Charles D.; Slevin, John T.; Kryscio, Richard J.; Martin, Catherine A.; Schmitt, Frederick A.; Blonder, Lee X.

    2015-01-01

    Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients. PMID:26793404

  13. Rumination and behavioural factors in Parkinson's disease depression

    PubMed Central

    Julien, Camille L.; Rimes, Katharine A.; Brown, Richard G.

    2016-01-01

    Objective Parkinson's disease is associated with high rates of depression. There is growing interest in non-pharmacological management including psychological approaches such as Cognitive Behaviour Therapy. To date, little research has investigated whether processes that underpin cognitive models of depression, on which such treatment is based, apply in patients with Parkinson's disease. The study aimed to investigate the contribution of core psychological factors to the presence and degree of depressive symptoms. Methods 104 participants completed questionnaires measuring mood, motor disability and core psychological variables, including maladaptive assumptions, rumination, cognitive-behavioural avoidance, illness representations and cognitive-behavioural responses to symptoms. Results Regression analyses revealed that a small number of psychological factors accounted for the majority of depression variance, over and above that explained by overall disability. Participants reporting high levels of rumination, avoidance and symptom focusing experienced more severe depressive symptoms. In contrast, pervasive negative dysfunctional beliefs did not independently contribute to depression variance. Conclusion Specific cognitive (rumination and symptom focusing) and behavioural (avoidance) processes may be key psychological markers of depression in Parkinson's disease and therefore offer important targets for tailored psychological interventions. PMID:26944399

  14. Dural arteriovenous fistula presenting with progressive dementia and parkinsonism

    PubMed Central

    Fujii, Hiroki; Nagano, Yoshito; Hosomi, Naohisa; Matsumoto, Masayasu

    2014-01-01

    We report a rare case of progressive parkinsonism and cognitive dysfunction due to dural arteriovenous fistula (DAVF). A 69-year-old man, with a history of hypertension and diabetes, was admitted to our hospital because of parkinsonism and dementia. Susceptibility-weighted imaging (SWI) revealed a thrombus in the superior sagittal sinus (SSS) and marked dilation of the medullary vein suggestive of the presence of comorbid DAVF. A single-photon emission CT (SPECT) showed widespread hypoperfusion in the bilateral frontal lobes. Selective cerebral angiography revealed a DAVF in SSS. These symptoms were significantly ameliorated following transvenous embolisation of the venous sinus at the shunting point. Reversible parkinsonism and dementia after embolisation was correlated with decreased dilation of medullary vein on SWI and improved cerebral blood flow on SPECT in the frontal lobes. Differentiation of parkinsonian and dementia symptoms due to DAVF from those associated with neurodegenerative disease is of great importance because DAVF-associated deficits may be reversed by endovascular therapy. PMID:24891481

  15. Parkinson's Disease: New research offers hope for better diagnosis and treatments | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Parkinson's Disease New Research Offers Hope for Better Diagnosis and ... As many as one million Americans live with Parkinson's disease (PD), which is more than the combined number ...

  16. Association analysis of a polymorphism of the monoamine oxidase B gene with Parkinson`s disease in a Japanese population

    SciTech Connect

    Morimoto, Yuji; Murayama, Nobuhiro; Kuwano, Akira; Kondo, Ikuko

    1995-12-18

    The polymorphic allele of the monoamine oxidase B (MAO-B) gene detected by polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP) was associated with Parkinson`s disease (PD) in Caucasians. We characterized this polymorphic allele, allele 1, of the MAO-B gene using direct sequencing of PCR products. A single DNA substitution (G-A), resulting gain of Mae III restriction site was detected in intron 13 of the MAO-B gene. The allele associated with PD in Caucasians was twice as frequent as in healthy Japanese, but the association of the allele of the MAO-B gene was not observed in Japanese patients with PD. 7 refs., 2 figs., 1 tab.

  17. Advances in GBA-associated Parkinson's disease--Pathology, presentation and therapies.

    PubMed

    Barkhuizen, Melinda; Anderson, David G; Grobler, Anne F

    2016-02-01

    GBA mutations are to date the most common genetic risk factor for Parkinson's disease. The GBA gene encodes the lysomal hydrolase glucocerebrosidase. Whilst bi-allelic GBA mutations cause Gaucher disease, both mono- and bi-allelic mutations confer risk for Parkinson's disease. Clinically, Parkinson's disease patients with GBA mutations resemble idiopathic Parkinson's disease patients. However, these patients have a modest reduction in age-of-onset of disease and a greater incidence of cognitive decline. In some cases, GBA mutations are also responsible for familial Parkinson's disease. The accumulation of α-synuclein into Lewy bodies is the central neuropathological hallmark of Parkinson's disease. Pathologic GBA mutations reduce enzymatic function. A reduction in glucocerebrosidase function increases α-synuclein levels and propagation, which in turn inhibits glucocerebrosidase in a feed-forward cascade. This cascade is central to the neuropathology of GBA-associated Parkinson's disease. The lysosomal integral membrane protein type-2 is necessary for normal glucocerebrosidase function. Glucocerebrosidase dysfunction also increases in the accumulation of β-amyloid and amyloid-precursor protein, oxidative stress, neuronal susceptibility to metal ions, microglial and immune activation. These factors contribute to neuronal death. The Mendelian Parkinson's disease genes, Parkin and ATP13A2, intersect with glucocerebrosidase. These factors sketch a complex circuit of GBA-associated neuropathology. To clinically interfere with this circuit, central glucocerebrosidase function must be improved. Strategies based on reducing breakdown of mutant glucocerebrosidase and increasing the fraction that reaches the lysosome has shown promise. Breakdown can be reduced by interfering with the ability of heat-shock proteins to recognize mutant glucocerebrosidase. This underlies the therapeutic efficacy of certain pharmacological chaperones and histone deacetylase inhibitors. These

  18. Age-specific Parkinson disease risk in GBA mutation carriers: information for genetic counseling

    PubMed Central

    Rana, Huma Q.; Balwani, Manisha; Bier, Louise; Alcalay, Roy N.

    2012-01-01

    Purpose We sought to estimate age-specific risk of Parkinson disease in relatives of patients with Gaucher disease, who are obligate carriers of GBA mutations and who were not ascertained by family history of Parkinson disease. Methods A validated family history of Parkinson disease questionnaire was administered to 119 patients with Gaucher disease who were evaluated at the Mount Sinai School of Medicine from 2009 to 2012; the ages of their parents, siblings, and children, history of Parkinson disease, age at onset of Parkinson disease, and ethnic background were obtained. Kaplan–Meier survival curves were used to estimate age-specific Parkinson disease penetrance among parents of patients with Gaucher disease, who are obligatory GBA mutation carriers. Results Two participants with Gaucher disease were affected by Parkinson disease (5.4% of those who were 60 years or older). Of the 224 informative parents of patients with Gaucher disease, 11 had Parkinson disease (4.9%). Among the parents (obligatory carriers), cumulative risk of Parkinson disease by ages 65 and 85 was estimated to be 2.2% ±2.1% and 10.9% ±7.2%, respectively. Conclusion We provide useful age-specific estimates of Parkinson disease penetrance in patients with Gaucher disease and GBA heterozygous carriers for genetic counseling. Although GBA mutations may increase the risk for PD, the vast majority of patients with Gaucher disease and heterozygotes may not develop the disease. Further studies are needed to identify what modifies the risk of Parkinson disease in GBA mutation carriers. PMID:22935721

  19. Genetic Identification Is Critical for the Diagnosis of Parkinsonism: A Chinese Pedigree with Early Onset of Parkinsonism

    PubMed Central

    Yang, Yang; Tang, Bei-sha; Weng, Ling; Li, Nan; Shen, Lu; Wang, Jian; Zuo, Chuan-tao; Yan, Xin-xiang; Xia, Kun; Guo, Ji-feng

    2015-01-01

    Background A number of hereditary neurological diseases display indistinguishable features at the early disease stage. Parkinsonian symptoms can be found in numerous diseases, making it difficult to get a definitive early diagnosis of primary causes for patients with onset of parkinsonism. The accurate and early diagnosis of the causes of parkinsonian patients is important for effective treatments of these patients. Methods We have identified a Chinese family (82 family members over four generations with 21 affected individuals) that manifested the characterized symptoms of parkinsonism and was initially diagnosed as Parkinson’s disease. We followed up with the family for two years, during which we carried out clinical observations, Positron Emission Tomography-Computed Tomography neuroimaging analysis, and exome sequencing to correctly diagnose the case. Results During the two-year follow-up period, we performed comprehensive medical history collection, physical examination, and structural and functional neuroimaging studies of this Chinese family. We found that the patient exhibited progressive deteriorated parkinsonism with Parkinson disease-like neuropathology and also had a good response to the initial levodopa treatment. However, exome sequencing identified a missense mutation, N279K, in exon 10 of MAPT gene, verifying that the early parkinsonian symptoms in this family are caused by the genetic mutation for hereditary frontotemporal lobar dementia. Conclusions For the inherited parkinsonian patients who even show the neuropathology similar to that in Parkinson’s disease and have initial response to levodopa treatment, genetic identification of the molecular basis for the disease is still required for defining the early diagnosis and correct treatment. PMID:26295349

  20. Acetaldehyde and parkinsonism: role of CYP450 2E1

    PubMed Central

    Vaglini, Francesca; Viaggi, Cristina; Piro, Valentina; Pardini, Carla; Gerace, Claudio; Scarselli, Marco; Corsini, Giovanni Umberto

    2013-01-01

    The present review update the relationship between acetaldehyde (ACE) and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly. We have indicated that ACE is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide (DAS) and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine (DA) neurons of rodent Substantia Nigra (SN), but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout (KO) mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the SN induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. ACE is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson's disease (PD) patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and PD. PMID:23801948

  1. A Comparative White Matter Study with Parkinson's disease, Parkinson's Disease with Dementia and Alzheimer's Disease

    PubMed Central

    Perea, Rodrigo D; Rada, Rebecca C; Wilson, Jessica; Vidoni, Eric D; Morris, Jill K; Lyons, Kelly E; Pahwa, Rajesh; Burns, Jeffrey M; Honea, Robyn A

    2014-01-01

    Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most common neurodegenerative disorders affecting older populations. AD is characterized by impaired memory and cognitive decline while the primary symptoms of PD include resting tremor, bradykinesia and rigidity. In PD, mild cognitive changes are frequently present, which could progress to dementia (PD dementia (PDD)). PDD and AD dementias are different in pathology although the difference in microstructural changes remains unknown. To further understand these diseases, it is essential to understand the distinct mechanism of their microstructural changes. We used diffusion tensor imaging (DTI) to investigate white matter tract differences between early stage individuals with AD (n=14), PD (n=12), PDD (n=9), and healthy non-demented controls (CON) (n=13). We used whole brain tract based spatial statistics (TBSS) and a region of interest (ROI) analysis focused on the substantia nigra (SN). We found that individuals with PDD had more widespread white matter degeneration compared to PD, AD, and CON. Individuals with AD had few regional abnormalities in the anterior and posterior projections of the corpus callosum while PD and CON did not appear to have significant white matter degeneration when compared to other groups. ROI analyses showed that PDD had the highest diffusivity in the SN and were significantly different from CON. There were no significant ROI differences between CON, PD, or AD. In conclusion, global white matter microstructural deterioration is evident in individuals with PDD, and DTI may provide a means with which to tease out pathological differences between AD and PD dementias. PMID:24724042

  2. Effects of Clay Manipulation on Somatic Dysfunction and Emotional Distress in Patients with Parkinson's Disease

    ERIC Educational Resources Information Center

    Elkis-Abuhoff, Deborah L.; Goldblatt, Robert B.; Gaydos, Morgan; Corrato, Samantha

    2008-01-01

    The focus of this outcome study was on art therapy as a support for medical treatment and palliative care. A total of 41 patients were placed in 2 matched groups: 22 patients with Parkinson's disease and 19 patients without Parkinson's disease. Each participant completed the Brief Symptom Inventory (BSI) (Derogatis, 1993) pre- and post-session,…

  3. Levodopa delivery systems for the treatment of Parkinson's disease: an overview.

    PubMed

    Goole, J; Amighi, K

    2009-10-01

    This review describes the different drug delivery systems containing levodopa that are used in the treatment of Parkinson's disease. Their composition, process of preparation, advantages, disadvantages and limitations are discussed as well as the major objective in the management of Parkinson's disease according to the pathology of the disease. PMID:19651197

  4. Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson's disease.

    PubMed

    Cho, Seung-Yeon; Shim, So-Ra; Rhee, Hak Young; Park, Hi-Joon; Jung, Woo-Sang; Moon, Sang-Kwan; Park, Jung-Mi; Ko, Chang-Nam; Cho, Ki-Ho; Park, Seong-Uk

    2012-09-01

    This study aimed to explore the effectiveness of both acupuncture and bee venom acupuncture as adjuvant therapies for idiopathic Parkinson's disease. We recruited 43 adults with idiopathic Parkinson's disease who had been on a stable dose of antiparkinsonian medication for at least 1 month. They were randomly assigned to 1 of 3 groups: acupuncture, bee venom acupuncture, or control. All participants were assessed using the Unified Parkinson's Disease Rating Scale, the Parkinson's Disease Quality of Life Questionnaire, the Beck Depression Inventory, the Berg Balance Scale, and the time and number of steps required to walk 30 m. Treatment groups underwent stimulation of 10 acupuncture points using acupuncture or bee venom acupuncture twice a week for 8 weeks. The initial assessment was repeated at the completion of treatment. The control group did not receive any treatment. Participants in the bee venom acupuncture group showed significant improvement on the Unified Parkinson's Disease Rating Scale (total score, as well as parts II and III individually), the Berg Balance Scale, and the 30 m walking time. When compared to the control group, the bee venom acupuncture group experienced significantly greater improvement on the Unified Parkinson's Disease Rating Scale. In the acupuncture group, the Unified Parkinson's Disease Rating Scale (part III and total scores) and the Beck Depression Inventory showed significant improvement. The control group showed no significant changes in any outcome after 8 weeks. In this pilot study, both acupuncture and bee venom acupuncture showed promising results as adjuvant therapies for Parkinson's disease. PMID:22632852

  5. Primary Health Care Providers' Knowledge Gaps on Parkinson's Disease

    ERIC Educational Resources Information Center

    Thompson, Megan R.; Stone, Ramona F.; Ochs, V. Dan; Litvan, Irene

    2013-01-01

    In order to determine primary health care providers' (PCPs) knowledge gaps on Parkinson's disease, data were collected before and after a one-hour continuing medical education (CME) lecture on early Parkinson's disease recognition and treatment from a sample of 104 PCPs participating at an annual meeting. The main outcome measure…

  6. Effect of Intensive Voice Treatment on Tone-Language Speakers with Parkinson's Disease

    ERIC Educational Resources Information Center

    Whitehill, Tara L.; Wong, Lina L. -N.

    2007-01-01

    The aim of this study was to investigate the effect of intensive voice therapy on Cantonese speakers with Parkinson's disease. The effect of the treatment on lexical tone was of particular interest. Four Cantonese speakers with idiopathic Parkinson's disease received treatment based on the principles of Lee Silverman Voice Treatment (LSVT).…

  7. Variability in Fundamental Frequency during Speech in Prodromal and Incipient Parkinson's Disease: A Longitudinal Case Study

    ERIC Educational Resources Information Center

    Harel, Brian; Cannizzaro, Michael; Snyder, Peter J.

    2004-01-01

    Nearly two centuries ago, Parkinson (1817) first observed that a particular pattern of speech changes occur in patients with idiopathic Parkinson's disease (PD). Numerous studies have documented these changes using a wide variety of acoustic measures, and yet few studies have attempted to quantify any such changes longitudinally, through the early…

  8. [Parkinson's disease associated with a mutation in the PARK2 gene].

    PubMed

    Kaasinen, Valtteri; Hietala, Marja; Kuoppamäki, Mikko

    2015-01-01

    The most common cause of monogenic hereditary Parkinson's disease is a mutation in the PARK2 gene. Early onset, slow progression, dystonia, and good response to levodopa are typical of the disease phenotype. Finnish PARK2 patients have not been described previously. We describe two patients, in whom pathogenic mutations in the PARK2 gene were the cause of parkinsonism. PMID:26245049

  9. Does Implicit Learning in Non-Demented Parkinson's Disease depend on the Level of Cognitive Functioning?

    ERIC Educational Resources Information Center

    Vandenbossche, Jochen; Deroost, Natacha; Soetens, Eric; Kerckhofs, Eric

    2009-01-01

    We investigated the influence of the level of cognitive functioning on sequence-specific learning in Parkinson's disease (PD). This was done by examining the relationship between the scales for outcomes in Parkinson's disease-cognition [SCOPA-COG, Marinus, J., Visser, M., Verwey, N. A., Verhey, F. R. J., Middelkoop, H. A. M.,Stiggelbout, A., et…

  10. Everyday Cognitive Failures and Memory Problems in Parkinson's Patients without Dementia

    ERIC Educational Resources Information Center

    Poliakoff, Ellen; Smith-Spark, James H.

    2008-01-01

    There is growing evidence that Parkinson's disease patients without dementia exhibit cognitive deficits in some executive, memory and selective attention tasks. However, the impact of these deficits on their everyday cognitive functioning remains largely unknown. This issue was explored using self-report questionnaires. Twenty-four Parkinson's…

  11. Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson's disease.

    PubMed

    Rolinski, Michal; Zokaei, Nahid; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E; Husain, Masud; Hu, Michele T M

    2016-01-01

    Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials. PMID:26582557

  12. Semantic Trouble Sources and Their Repair in Conversations Affected by Parkinson's Disease

    ERIC Educational Resources Information Center

    Saldert, Charlotta; Ferm, Ulrika; Bloch, Steven

    2014-01-01

    Background: It is known that dysarthria arising from Parkinson's disease may affect intelligibility in conversational interaction. Research has also shown that Parkinson's disease may affect cognition and cause word-retrieval difficulties and pragmatic problems in the use of language. However, it is not known whether or how these…

  13. TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF.

    PubMed

    Nam, Jin H; Park, Eun S; Won, So-Yoon; Lee, Yu A; Kim, Kyoung I; Jeong, Jae Y; Baek, Jeong Y; Cho, Eun J; Jin, Minyoung; Chung, Young C; Lee, Byoung D; Kim, Sung Hyun; Kim, Eung-Gook; Byun, Kyunghee; Lee, Bonghee; Woo, Dong Ho; Lee, C Justin; Kim, Sang R; Bok, Eugene; Kim, Yoon-Seong; Ahn, Tae-Beom; Ko, Hyuk Wan; Brahmachari, Saurav; Pletinkova, Olga; Troconso, Juan C; Dawson, Valina L; Dawson, Ted M; Jin, Byung K

    2015-12-01

    Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease. PMID:26490328

  14. New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases

    PubMed Central

    Hölscher, Christian

    2014-01-01

    Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer's disease and Parkinson's disease. On the basis of these promising findings, several clinical trials are ongoing with the first encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer's disease and Parkinson's disease that are currently unavailable. PMID:25558231

  15. Successful birth of an IVF baby in a patient with Parkinson's disease.

    PubMed

    Asha, Baxi; Hansali, Neema; Apoorva, Pauranik

    2010-01-01

    Parkinson's disease, although rare in young patients, may be encountered in the reproductive age group. We report a rare combination of this disease with infertility, which has not been previously reported. The case record of a 29-year-old woman with infertility and Parkinson's disease are retrospectively reviewed. An IVF indicated for tubal factor infertility resulted in a successful singleton pregnancy. She delivered a healthy male baby without experiencing any worsening of her Parkinsonism. The course of pregnancy remained unaffected by the Parkinson's disease and anti-Parkinsonian drugs. The details of the infertility management, antenatal and postnatal course, and medications are described. With careful evaluation, counseling, and monitoring, IVF may be safely used in women with Parkinson's disease. PMID:20607009

  16. Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Jansson, Daniel; Medvedev, Alexander; Axelson, Hans; Nyholm, Dag

    2013-10-01

    Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson's disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener-type model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patientts with Parkinson's disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects attempting to track visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson's disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson's disease.

  17. Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application

    PubMed Central

    2016-01-01

    Parkinson's disease is a neurodegenerative disease/synucleinopathy that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars compacta and widespread aggregation of the α-synuclein protein (encoded by the SNCA gene) in the form of Lewy bodies and Lewy neurites are the neuropathological hallmarks of Parkinson's disease. The SNCA gene has undergone gene duplications, triplications, and point mutations. However, the specific mechanism of α-synuclein in Parkinson's disease remains obscure. Recent research showed that various α-synuclein oligomers, pathological aggregation, and propagation appear to be harmful in certain areas in Parkinson's disease patients. This review summarizes our current knowledge of the pathogenetic dysfunction of α-synuclein associated with Parkinson's disease and highlights current approaches that seek to develop this protein as a possible diagnostic biomarker and therapeutic target. PMID:27610264

  18. [Movement from the social cognitive neuroscience: The case of Parkinson's disease].

    PubMed

    Bacigalupe, María de Los Ángeles; Pujol, Silvana

    2014-01-01

    Parkinson's disease is a multisystemic disorder that affects movement in its different levels of integration from the simplest motor act to the complexity of communication and social inclusion. The study of movement from the social cognitive neuroscience can contribute elements to the development of better rehabilitation treatments for Parkinson's disease patients. As a cognitive and social phenomenon, movement involves perception and action; paradoxical kinesia, as a property of motor system, is shown in this perception-action dialogue. We introduce the internal-external control hypothesis as a possible explanatory model of movement in Parkinson's disease patients. This model can explain the occurrence of paradoxical kinesia and, combined with the mirror neurons theory, accounts for the capability of people with Parkinson's disease to move like healthy controls do when there is a given sensorial space with emotional and ludic languages. Eventually, we highlight the utility of paradoxical kinesia as a rehabilitation tool for movement in people with Parkinson's disease. PMID:26098822

  19. DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease

    NASA Astrophysics Data System (ADS)

    Lin, Xiangmin; Cook, Travis J.; Zabetian, Cyrus P.; Leverenz, James B.; Peskind, Elaine R.; Hu, Shu-Ching; Cain, Kevin C.; Pan, Catherine; Edgar, John Scott; Goodlett, David R.; Racette, Brad A.; Checkoway, Harvey; Montine, Thomas J.; Shi, Min; Zhang, Jing

    2012-12-01

    DJ-1 is a multifunctional protein that plays an important role in oxidative stress, cell death, and synucleinopathies, including Parkinson disease. Previous studies have demonstrated that total DJ-1 levels decrease in the cerebrospinal fluid, but do not change significantly in human plasma from patients with Parkinson disease when compared with controls. In this study, we measured total DJ-1 and its isoforms in whole blood of patients with Parkinson disease at various stages, Alzheimer disease, and healthy controls to identify potential peripheral biomarkers of PD. In an initial discovery study of 119 subjects, 7 DJ-1 isoforms were reliably detected, and blood levels of those with 4-hydroxy-2-nonenal modifications were discovered to be altered in late-stage Parkinson disease. This result was further confirmed in a validation study of another 114 participants, suggesting that, unlike total DJ-1 levels, post-translationally modified isoforms of DJ-1 from whole blood are candidate biomarkers of late-stage Parkinson disease.

  20. Standardized Handwriting to Assess Bradykinesia, Micrographia and Tremor in Parkinson's Disease

    PubMed Central

    Smits, Esther J.; Tolonen, Antti J.; Cluitmans, Luc; van Gils, Mark; Conway, Bernard A.; Zietsma, Rutger C.; Leenders, Klaus L.; Maurits, Natasha M.

    2014-01-01

    Objective To assess whether standardized handwriting can provide quantitative measures to distinguish patients diagnosed with Parkinson's disease from age- and gender-matched healthy control participants. Design Exploratory study. Pen tip trajectories were recorded during circle, spiral and line drawing and repeated character ‘elelelel’ and sentence writing, performed by Parkinson patients and healthy control participants. Parkinson patients were tested after overnight withdrawal of anti-Parkinsonian medication. Setting University Medical Center Groningen, tertiary care, the Netherlands. Participants Patients with Parkinson's disease (n = 10; mean age 69.0 years; 6 male) and healthy controls (n = 10; mean age 68.1 years; 6 male). Interventions Not applicable. Main Outcome Measures Movement time and velocity to detect bradykinesia and the size of writing to detect micrographia. A rest recording to investigate the presence of a rest-tremor, by frequency analysis. Results Mean disease duration in the Parkinson group was 4.4 years and the patients were in modified Hoehn-Yahr stages 1–2.5. In general, Parkinson patients were slower than healthy control participants. Median time per repetition, median velocity and median acceleration of the sentence task and median velocity of the elel task differed significantly between Parkinson patients and healthy control participants (all p<0.0014). Parkinson patients also wrote smaller than healthy control participants and the width of the ‘e’ in the elel task was significantly smaller in Parkinson patients compared to healthy control participants (p<0.0014). A rest-tremor was detected in the three patients who were clinically assessed as having rest-tremor. Conclusions This study shows that standardized handwriting can provide objective measures for bradykinesia, tremor and micrographia to distinguish Parkinson patients from healthy control participants. PMID:24854199